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Hematology is in the Brodsky family’s blood
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
FROM ASH 2023
Underdiagnosed: Iron deficiency anemia during pregnancy
Jerome J. Federspiel, MD, often cares for patients who are about to deliver a baby but who have untreated iron deficiency anemia (IDA). Often, these patients require a blood transfusion after giving birth.
“I am sad to hear commonly from patients we treat that they have had iron-deficient anemia symptoms for many years. Correcting these conditions makes birth safer and, oftentimes, makes people feel much better – sometimes better than they have in years,” Dr. Federspiel, maternal-fetal medicine physician and assistant professor of obstetrics and gynecology and population health sciences at Duke University, Durham, N.C., said.
Even patients he is able to diagnose earlier “will have difficulties catching up during pregnancy.”
The condition is the most common type of anemia among people who are pregnant. IDA increases a patient’s risk of delivering preterm and developing postpartum depression and puts their infants at a risk for perinatal mortality. Without proper treatment of IDA throughout pregnancy, the condition can also lead to low birth weights in infants or failing to meet weight goals later on.
But of all women with a new diagnosis of IDA from 2021 to 2022, 10% were pregnant, according to an analysis by Komodo Health, a health care analytics company.
While estimates of the prevalence of IDA vary, research from 2021 found 6.5% of nearly 1,500 patients who were pregnant during the first trimester had the condition, a figure the researchers said might underrepresent the problem.
“In severe cases [fetal outcomes can include] abnormal fetal oxygenation, nonreassuring fetal heart rate patterns, reduced amniotic fluid volume, fetal cerebral vasodilation, and fetal death,” Alianne S. Tilley, NP, family nurse practitioner at Women’s Care of Lake Cumberland, Somerset, Ky., said.
Research has shown that adequate levels of iron are an integral component in the development of the fetal brain. Some studies have reported that IDA during pregnancy increases an infant’s risk for poor neurodevelopmental outcomes.
Lack of screening protocol
Discrepancies in guidance for testing patients who are pregnant for IDA may add to late diagnosis and low treatment, according to Katelin Zahn, MD, assistant professor of general obstetrics, gynecology, and midwifery at University of North Carolina at Chapel Hill.
“There’s no consistency, which leads to a lot of variation in individual practice, which creates variation in outcomes, too,” Dr. Zahn said. “You can only do so much as one independent physician, and you need to be able to create change in a system that functions and provides standard of care even when you aren’t there.”
The American College of Obstetricians and Gynecologists recommends screening all patients who are pregnant with a complete blood count in the first trimester and again between 24 and 27 weeks of gestation.
Patients who meet criteria for IDA based on hematocrit levels less than 33% in the first and third trimesters, and less than 32% in the second trimester, should be evaluated to determine the cause. Those with IDA should be treated with supplemental iron, in addition to prenatal vitamins, ACOG says.
But the U.S. Preventive Services Task Force in 2015 found insufficient evidence to recommend for or against screening patients without symptoms or signs of the condition. The organization is in the process of updating the recommendation.
Prevention as best practice
The most effective way to address IDA in patients who are pregnant is prevention, according to Dr. Federspiel.
“Having a systematic approach to screening and treatment is really important, and this starts before pregnancy,” Dr. Federspiel said. “On average, a typical pregnancy requires an additional 1 g of iron.”
Dr. Federspiel recommends clinicians discuss the causes and the effects of IDA with patients who are planning to or could become pregnant. Clinicians might recommend iron- and folate-rich foods and vitamins B12 and C and ask patients if they face any barriers to access.
“Prenatal vitamins with iron are the gold standard in preventing IDA in the pregnant population,” Ms. Tilley said. “Education on the significant risk factors associated with IDA in early pregnancy is key.”
A version of this article first appeared on Medscape.com.
Jerome J. Federspiel, MD, often cares for patients who are about to deliver a baby but who have untreated iron deficiency anemia (IDA). Often, these patients require a blood transfusion after giving birth.
“I am sad to hear commonly from patients we treat that they have had iron-deficient anemia symptoms for many years. Correcting these conditions makes birth safer and, oftentimes, makes people feel much better – sometimes better than they have in years,” Dr. Federspiel, maternal-fetal medicine physician and assistant professor of obstetrics and gynecology and population health sciences at Duke University, Durham, N.C., said.
Even patients he is able to diagnose earlier “will have difficulties catching up during pregnancy.”
The condition is the most common type of anemia among people who are pregnant. IDA increases a patient’s risk of delivering preterm and developing postpartum depression and puts their infants at a risk for perinatal mortality. Without proper treatment of IDA throughout pregnancy, the condition can also lead to low birth weights in infants or failing to meet weight goals later on.
But of all women with a new diagnosis of IDA from 2021 to 2022, 10% were pregnant, according to an analysis by Komodo Health, a health care analytics company.
While estimates of the prevalence of IDA vary, research from 2021 found 6.5% of nearly 1,500 patients who were pregnant during the first trimester had the condition, a figure the researchers said might underrepresent the problem.
“In severe cases [fetal outcomes can include] abnormal fetal oxygenation, nonreassuring fetal heart rate patterns, reduced amniotic fluid volume, fetal cerebral vasodilation, and fetal death,” Alianne S. Tilley, NP, family nurse practitioner at Women’s Care of Lake Cumberland, Somerset, Ky., said.
Research has shown that adequate levels of iron are an integral component in the development of the fetal brain. Some studies have reported that IDA during pregnancy increases an infant’s risk for poor neurodevelopmental outcomes.
Lack of screening protocol
Discrepancies in guidance for testing patients who are pregnant for IDA may add to late diagnosis and low treatment, according to Katelin Zahn, MD, assistant professor of general obstetrics, gynecology, and midwifery at University of North Carolina at Chapel Hill.
“There’s no consistency, which leads to a lot of variation in individual practice, which creates variation in outcomes, too,” Dr. Zahn said. “You can only do so much as one independent physician, and you need to be able to create change in a system that functions and provides standard of care even when you aren’t there.”
The American College of Obstetricians and Gynecologists recommends screening all patients who are pregnant with a complete blood count in the first trimester and again between 24 and 27 weeks of gestation.
Patients who meet criteria for IDA based on hematocrit levels less than 33% in the first and third trimesters, and less than 32% in the second trimester, should be evaluated to determine the cause. Those with IDA should be treated with supplemental iron, in addition to prenatal vitamins, ACOG says.
But the U.S. Preventive Services Task Force in 2015 found insufficient evidence to recommend for or against screening patients without symptoms or signs of the condition. The organization is in the process of updating the recommendation.
Prevention as best practice
The most effective way to address IDA in patients who are pregnant is prevention, according to Dr. Federspiel.
“Having a systematic approach to screening and treatment is really important, and this starts before pregnancy,” Dr. Federspiel said. “On average, a typical pregnancy requires an additional 1 g of iron.”
Dr. Federspiel recommends clinicians discuss the causes and the effects of IDA with patients who are planning to or could become pregnant. Clinicians might recommend iron- and folate-rich foods and vitamins B12 and C and ask patients if they face any barriers to access.
“Prenatal vitamins with iron are the gold standard in preventing IDA in the pregnant population,” Ms. Tilley said. “Education on the significant risk factors associated with IDA in early pregnancy is key.”
A version of this article first appeared on Medscape.com.
Jerome J. Federspiel, MD, often cares for patients who are about to deliver a baby but who have untreated iron deficiency anemia (IDA). Often, these patients require a blood transfusion after giving birth.
“I am sad to hear commonly from patients we treat that they have had iron-deficient anemia symptoms for many years. Correcting these conditions makes birth safer and, oftentimes, makes people feel much better – sometimes better than they have in years,” Dr. Federspiel, maternal-fetal medicine physician and assistant professor of obstetrics and gynecology and population health sciences at Duke University, Durham, N.C., said.
Even patients he is able to diagnose earlier “will have difficulties catching up during pregnancy.”
The condition is the most common type of anemia among people who are pregnant. IDA increases a patient’s risk of delivering preterm and developing postpartum depression and puts their infants at a risk for perinatal mortality. Without proper treatment of IDA throughout pregnancy, the condition can also lead to low birth weights in infants or failing to meet weight goals later on.
But of all women with a new diagnosis of IDA from 2021 to 2022, 10% were pregnant, according to an analysis by Komodo Health, a health care analytics company.
While estimates of the prevalence of IDA vary, research from 2021 found 6.5% of nearly 1,500 patients who were pregnant during the first trimester had the condition, a figure the researchers said might underrepresent the problem.
“In severe cases [fetal outcomes can include] abnormal fetal oxygenation, nonreassuring fetal heart rate patterns, reduced amniotic fluid volume, fetal cerebral vasodilation, and fetal death,” Alianne S. Tilley, NP, family nurse practitioner at Women’s Care of Lake Cumberland, Somerset, Ky., said.
Research has shown that adequate levels of iron are an integral component in the development of the fetal brain. Some studies have reported that IDA during pregnancy increases an infant’s risk for poor neurodevelopmental outcomes.
Lack of screening protocol
Discrepancies in guidance for testing patients who are pregnant for IDA may add to late diagnosis and low treatment, according to Katelin Zahn, MD, assistant professor of general obstetrics, gynecology, and midwifery at University of North Carolina at Chapel Hill.
“There’s no consistency, which leads to a lot of variation in individual practice, which creates variation in outcomes, too,” Dr. Zahn said. “You can only do so much as one independent physician, and you need to be able to create change in a system that functions and provides standard of care even when you aren’t there.”
The American College of Obstetricians and Gynecologists recommends screening all patients who are pregnant with a complete blood count in the first trimester and again between 24 and 27 weeks of gestation.
Patients who meet criteria for IDA based on hematocrit levels less than 33% in the first and third trimesters, and less than 32% in the second trimester, should be evaluated to determine the cause. Those with IDA should be treated with supplemental iron, in addition to prenatal vitamins, ACOG says.
But the U.S. Preventive Services Task Force in 2015 found insufficient evidence to recommend for or against screening patients without symptoms or signs of the condition. The organization is in the process of updating the recommendation.
Prevention as best practice
The most effective way to address IDA in patients who are pregnant is prevention, according to Dr. Federspiel.
“Having a systematic approach to screening and treatment is really important, and this starts before pregnancy,” Dr. Federspiel said. “On average, a typical pregnancy requires an additional 1 g of iron.”
Dr. Federspiel recommends clinicians discuss the causes and the effects of IDA with patients who are planning to or could become pregnant. Clinicians might recommend iron- and folate-rich foods and vitamins B12 and C and ask patients if they face any barriers to access.
“Prenatal vitamins with iron are the gold standard in preventing IDA in the pregnant population,” Ms. Tilley said. “Education on the significant risk factors associated with IDA in early pregnancy is key.”
A version of this article first appeared on Medscape.com.
Unexplained collapse unveils rare blood disorder
This case report was published in the New England Journal of Medicine.
Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.
The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.
During the examination, her vital signs were within normal ranges.
The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.
Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.
In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).
Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.
After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.
While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.
A version of this article first appeared on Medscape.com.
This case report was published in the New England Journal of Medicine.
Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.
The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.
During the examination, her vital signs were within normal ranges.
The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.
Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.
In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).
Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.
After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.
While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.
A version of this article first appeared on Medscape.com.
This case report was published in the New England Journal of Medicine.
Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.
The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.
During the examination, her vital signs were within normal ranges.
The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.
Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.
In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).
Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.
After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.
While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Children with sickle cell disease at risk for vision loss
Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.
Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.
Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.
“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.
The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.
Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.
“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.
Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.
Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.
“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.
The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.
Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.
“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.
Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.
Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.
“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.
The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.
Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.
“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAO 2023
Dispelling clinicians’ misconceptions about sickle cell disease
Affecting more than 20 million people globally and 100,000 people nationwide, SCD is the most common inherited blood disorder in the United States. It occurs largely but not exclusively among people of African descent.
Patients with SCD develop crescent-shaped or “sickled” red blood cells that, unlike normally round cells, can potentially block blood flow and thus cause a host of problems ranging from a risk of stroke or infections to sometimes severe pain crises, called vaso-occlusive episodes.
To help ward off such complications, some key preventative measures and an array of therapies have become available in recent years: Newborn screening and prophylaxis, including the introduction of pneumococcal vaccines, have substantially reduced rates of invasive pneumococcal infection, which previously accounted for 32% of all causes of death in patients with SCD under the age of 20.
And while hydroxyurea was the only medication from 1998 to 2017 to alleviate acute pain episodes in SCD, newer options have become available in recent years, with l-glutamine, voxelotor, and crizanlizumab gaining FDA approval to further help prevent the episodes.
However, studies show that many if not most patients fail to receive adequate treatment, with one recent report indicating that, between 2016 and 2020, hydroxyurea was prescribed to fewer than 25% of patients with SCD, and fewer than 4% of people with the disease who experience chronic pain episodes had prescriptions for the newer FDA-approved drugs.
Myths and truths
To help clarify some common misconceptions that contribute to the problems, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, detailed some of the most prevalent and persistent myths among clinicians about SCD:
Pain level
Myths: Firstly, that sickle cell pain is not that bad, and patients therefore don’t really need opioid pain treatment, and secondly, that sickle cell pain is measurable by lab tests, such as the number of sickled red blood cells on a blood smear, reticulocytes, or hemoglobin level.
Truths: “Sickle cell vaso-occlusive pain can be very severe – a 10 on a scale of 10 – but the pain is usually only known by subjective report,” said Dr. Hsu, a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“No lab test can be used to measure pain,” he said. “Other lab tests can be abnormal, and some have statistical correlation with lifetime severity of disease course, but the lab tests are not for determination of acute level of pain or absence of pain.”
Blacks only
Myth: SCD only affects Black people.
Truth: People who have sickle cell disease from many ethnic backgrounds and skin colors.
“Around the Mediterranean, there are sickle cell patients from Greece, Turkey, Italy, and Spain. Some are blond and blue-eyed. People in India and Pakistan have sickle cell disease,” Dr. Hsu explained.
In addition, “people from the Arabian Peninsula have sickle cell disease; some Malaysians have sickle cell disease; one child who is about third generation in Hong Kong has sickle cell disease.”
Parental link
Myth: Sickle cell disease only occurs in individuals both of whose parents have the sickle gene.
Truth: “There are types of sickle cell disease [involving] a sickle cell gene from one parent and a gene for hemoglobin C from the other parent,” Dr. Hsu noted. “Others inherited one sickle gene [from one parent] and inherited from the other parent a gene for beta thalassemia. Others involve an inherited sickle gene and hemoglobin E; others have inherited one sickle gene and inherited a gene for hemoglobin D-Punjab, while others have sickle and hemoglobin O-Arab.”
Effects beyond pain
Myth: A person who is not having sickle cell pain is otherwise not significantly affected by their disease.
Truth: “Organs can be damaged silently every day,” Dr. Hsu said. “Kidney failure, retina damage, and pulmonary hypertension are the most notable of organ systems that can suffer damage for a long time without symptoms, then develop symptoms when it is too late to intervene.”
“For this reason, individuals with sickle cell disease should have regular expert care for health maintenance that is disease specific,” Dr. Hsu added.
Consult guidelines
One final concern is a basic failure to utilize critical information sources and guidelines, especially by primary care providers and/or other nonspecialists from whom patients with SCD may often seek treatment. “Awareness of these guidelines is low,” Dr. Hsu said.
Key resources that can be helpful include evidence-based guidelines developed by an expert panel of the National Heart, Lung, and Blood Institute, and the American Society of Hematology has a Pocket Guide app on management of sickle cell disease.
Another key resource being highlighted in September, which is National Sickle Cell Disease Awareness Month, is the NHLBI’s comprehensive website, providing information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with SCD.
“We are trying to bring more sickle cell information and case studies into medical school curricula, nursing curricula, social workers and community health workers awareness, [and] apps and online guidelines are proliferating,” Dr. Hsu says.
He goes on to say, “We need more recognition and resources from insurance providers that quality care for sickle cell disease is measured and rewarded.”
Dr. Hsu coauthored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He reported relationships with Novartis, Emmaus, Forma Therapeutic, Dupont/Nemours Children’s Hospital, Hilton Publishing, Asklepion, Bayer, CRISPR/Vertex, Cyclerion, Pfizer, and Aruvant.
Affecting more than 20 million people globally and 100,000 people nationwide, SCD is the most common inherited blood disorder in the United States. It occurs largely but not exclusively among people of African descent.
Patients with SCD develop crescent-shaped or “sickled” red blood cells that, unlike normally round cells, can potentially block blood flow and thus cause a host of problems ranging from a risk of stroke or infections to sometimes severe pain crises, called vaso-occlusive episodes.
To help ward off such complications, some key preventative measures and an array of therapies have become available in recent years: Newborn screening and prophylaxis, including the introduction of pneumococcal vaccines, have substantially reduced rates of invasive pneumococcal infection, which previously accounted for 32% of all causes of death in patients with SCD under the age of 20.
And while hydroxyurea was the only medication from 1998 to 2017 to alleviate acute pain episodes in SCD, newer options have become available in recent years, with l-glutamine, voxelotor, and crizanlizumab gaining FDA approval to further help prevent the episodes.
However, studies show that many if not most patients fail to receive adequate treatment, with one recent report indicating that, between 2016 and 2020, hydroxyurea was prescribed to fewer than 25% of patients with SCD, and fewer than 4% of people with the disease who experience chronic pain episodes had prescriptions for the newer FDA-approved drugs.
Myths and truths
To help clarify some common misconceptions that contribute to the problems, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, detailed some of the most prevalent and persistent myths among clinicians about SCD:
Pain level
Myths: Firstly, that sickle cell pain is not that bad, and patients therefore don’t really need opioid pain treatment, and secondly, that sickle cell pain is measurable by lab tests, such as the number of sickled red blood cells on a blood smear, reticulocytes, or hemoglobin level.
Truths: “Sickle cell vaso-occlusive pain can be very severe – a 10 on a scale of 10 – but the pain is usually only known by subjective report,” said Dr. Hsu, a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“No lab test can be used to measure pain,” he said. “Other lab tests can be abnormal, and some have statistical correlation with lifetime severity of disease course, but the lab tests are not for determination of acute level of pain or absence of pain.”
Blacks only
Myth: SCD only affects Black people.
Truth: People who have sickle cell disease from many ethnic backgrounds and skin colors.
“Around the Mediterranean, there are sickle cell patients from Greece, Turkey, Italy, and Spain. Some are blond and blue-eyed. People in India and Pakistan have sickle cell disease,” Dr. Hsu explained.
In addition, “people from the Arabian Peninsula have sickle cell disease; some Malaysians have sickle cell disease; one child who is about third generation in Hong Kong has sickle cell disease.”
Parental link
Myth: Sickle cell disease only occurs in individuals both of whose parents have the sickle gene.
Truth: “There are types of sickle cell disease [involving] a sickle cell gene from one parent and a gene for hemoglobin C from the other parent,” Dr. Hsu noted. “Others inherited one sickle gene [from one parent] and inherited from the other parent a gene for beta thalassemia. Others involve an inherited sickle gene and hemoglobin E; others have inherited one sickle gene and inherited a gene for hemoglobin D-Punjab, while others have sickle and hemoglobin O-Arab.”
Effects beyond pain
Myth: A person who is not having sickle cell pain is otherwise not significantly affected by their disease.
Truth: “Organs can be damaged silently every day,” Dr. Hsu said. “Kidney failure, retina damage, and pulmonary hypertension are the most notable of organ systems that can suffer damage for a long time without symptoms, then develop symptoms when it is too late to intervene.”
“For this reason, individuals with sickle cell disease should have regular expert care for health maintenance that is disease specific,” Dr. Hsu added.
Consult guidelines
One final concern is a basic failure to utilize critical information sources and guidelines, especially by primary care providers and/or other nonspecialists from whom patients with SCD may often seek treatment. “Awareness of these guidelines is low,” Dr. Hsu said.
Key resources that can be helpful include evidence-based guidelines developed by an expert panel of the National Heart, Lung, and Blood Institute, and the American Society of Hematology has a Pocket Guide app on management of sickle cell disease.
Another key resource being highlighted in September, which is National Sickle Cell Disease Awareness Month, is the NHLBI’s comprehensive website, providing information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with SCD.
“We are trying to bring more sickle cell information and case studies into medical school curricula, nursing curricula, social workers and community health workers awareness, [and] apps and online guidelines are proliferating,” Dr. Hsu says.
He goes on to say, “We need more recognition and resources from insurance providers that quality care for sickle cell disease is measured and rewarded.”
Dr. Hsu coauthored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He reported relationships with Novartis, Emmaus, Forma Therapeutic, Dupont/Nemours Children’s Hospital, Hilton Publishing, Asklepion, Bayer, CRISPR/Vertex, Cyclerion, Pfizer, and Aruvant.
Affecting more than 20 million people globally and 100,000 people nationwide, SCD is the most common inherited blood disorder in the United States. It occurs largely but not exclusively among people of African descent.
Patients with SCD develop crescent-shaped or “sickled” red blood cells that, unlike normally round cells, can potentially block blood flow and thus cause a host of problems ranging from a risk of stroke or infections to sometimes severe pain crises, called vaso-occlusive episodes.
To help ward off such complications, some key preventative measures and an array of therapies have become available in recent years: Newborn screening and prophylaxis, including the introduction of pneumococcal vaccines, have substantially reduced rates of invasive pneumococcal infection, which previously accounted for 32% of all causes of death in patients with SCD under the age of 20.
And while hydroxyurea was the only medication from 1998 to 2017 to alleviate acute pain episodes in SCD, newer options have become available in recent years, with l-glutamine, voxelotor, and crizanlizumab gaining FDA approval to further help prevent the episodes.
However, studies show that many if not most patients fail to receive adequate treatment, with one recent report indicating that, between 2016 and 2020, hydroxyurea was prescribed to fewer than 25% of patients with SCD, and fewer than 4% of people with the disease who experience chronic pain episodes had prescriptions for the newer FDA-approved drugs.
Myths and truths
To help clarify some common misconceptions that contribute to the problems, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, detailed some of the most prevalent and persistent myths among clinicians about SCD:
Pain level
Myths: Firstly, that sickle cell pain is not that bad, and patients therefore don’t really need opioid pain treatment, and secondly, that sickle cell pain is measurable by lab tests, such as the number of sickled red blood cells on a blood smear, reticulocytes, or hemoglobin level.
Truths: “Sickle cell vaso-occlusive pain can be very severe – a 10 on a scale of 10 – but the pain is usually only known by subjective report,” said Dr. Hsu, a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“No lab test can be used to measure pain,” he said. “Other lab tests can be abnormal, and some have statistical correlation with lifetime severity of disease course, but the lab tests are not for determination of acute level of pain or absence of pain.”
Blacks only
Myth: SCD only affects Black people.
Truth: People who have sickle cell disease from many ethnic backgrounds and skin colors.
“Around the Mediterranean, there are sickle cell patients from Greece, Turkey, Italy, and Spain. Some are blond and blue-eyed. People in India and Pakistan have sickle cell disease,” Dr. Hsu explained.
In addition, “people from the Arabian Peninsula have sickle cell disease; some Malaysians have sickle cell disease; one child who is about third generation in Hong Kong has sickle cell disease.”
Parental link
Myth: Sickle cell disease only occurs in individuals both of whose parents have the sickle gene.
Truth: “There are types of sickle cell disease [involving] a sickle cell gene from one parent and a gene for hemoglobin C from the other parent,” Dr. Hsu noted. “Others inherited one sickle gene [from one parent] and inherited from the other parent a gene for beta thalassemia. Others involve an inherited sickle gene and hemoglobin E; others have inherited one sickle gene and inherited a gene for hemoglobin D-Punjab, while others have sickle and hemoglobin O-Arab.”
Effects beyond pain
Myth: A person who is not having sickle cell pain is otherwise not significantly affected by their disease.
Truth: “Organs can be damaged silently every day,” Dr. Hsu said. “Kidney failure, retina damage, and pulmonary hypertension are the most notable of organ systems that can suffer damage for a long time without symptoms, then develop symptoms when it is too late to intervene.”
“For this reason, individuals with sickle cell disease should have regular expert care for health maintenance that is disease specific,” Dr. Hsu added.
Consult guidelines
One final concern is a basic failure to utilize critical information sources and guidelines, especially by primary care providers and/or other nonspecialists from whom patients with SCD may often seek treatment. “Awareness of these guidelines is low,” Dr. Hsu said.
Key resources that can be helpful include evidence-based guidelines developed by an expert panel of the National Heart, Lung, and Blood Institute, and the American Society of Hematology has a Pocket Guide app on management of sickle cell disease.
Another key resource being highlighted in September, which is National Sickle Cell Disease Awareness Month, is the NHLBI’s comprehensive website, providing information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with SCD.
“We are trying to bring more sickle cell information and case studies into medical school curricula, nursing curricula, social workers and community health workers awareness, [and] apps and online guidelines are proliferating,” Dr. Hsu says.
He goes on to say, “We need more recognition and resources from insurance providers that quality care for sickle cell disease is measured and rewarded.”
Dr. Hsu coauthored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He reported relationships with Novartis, Emmaus, Forma Therapeutic, Dupont/Nemours Children’s Hospital, Hilton Publishing, Asklepion, Bayer, CRISPR/Vertex, Cyclerion, Pfizer, and Aruvant.
Pediatrician with SCD gives her young patients hope
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
FDA approves JAK inhibitor momelotinib for myelofibrosis with anemia
Momelotinib is the fourth JAK inhibitor to be approved by the agency for myelofibrosis but the only one indicated for patients with hemoglobin levels below 10 g/dL.
It’s an important development because, while JAK inhibitors are standard treatment for myelofibrosis, those previously approved for the uncommon blood cancer can cause cytopenia, particularly anemia, which, ironically, is also a hallmark of myelofibrosis itself.
This issue makes using JAK inhibitors for myelofibrosis challenging, according to Anthony Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta, who spoke on the topic recently at the annual meeting of the Society of Hematologic Oncology in Houston. “Momelotinib is an important emerging agent for these more anemic patients.” Momelotinib has a spleen response comparable with ruxolitinib – the first JAK inhibitor approved for myelofibrosis in the United States – and significantly higher rates of transfusion independence, although lower rates of symptom control, he said.
In GSK’s press release, hematologist/oncologist Ruben Mesa, MD, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, N.C., said that, “with momelotinib, we have the potential to establish a new standard of care for myelofibrosis patients with anemia.”
Momelotinib’s specific indication is for “the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia.”
The once-daily oral medication was approved based on two trials. One trial, MOMENTUM, showed statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in anemic patients treated with momelotinib versus danazol.
An anemic subset of the SIMPLIFY-1 trial showed comparable spleen volume reduction versus ruxolitinib but a numerically lower symptom response rate.
The most common momelotinib adverse reactions in trials were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
A version of this article appeared on Medscape.com.
Momelotinib is the fourth JAK inhibitor to be approved by the agency for myelofibrosis but the only one indicated for patients with hemoglobin levels below 10 g/dL.
It’s an important development because, while JAK inhibitors are standard treatment for myelofibrosis, those previously approved for the uncommon blood cancer can cause cytopenia, particularly anemia, which, ironically, is also a hallmark of myelofibrosis itself.
This issue makes using JAK inhibitors for myelofibrosis challenging, according to Anthony Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta, who spoke on the topic recently at the annual meeting of the Society of Hematologic Oncology in Houston. “Momelotinib is an important emerging agent for these more anemic patients.” Momelotinib has a spleen response comparable with ruxolitinib – the first JAK inhibitor approved for myelofibrosis in the United States – and significantly higher rates of transfusion independence, although lower rates of symptom control, he said.
In GSK’s press release, hematologist/oncologist Ruben Mesa, MD, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, N.C., said that, “with momelotinib, we have the potential to establish a new standard of care for myelofibrosis patients with anemia.”
Momelotinib’s specific indication is for “the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia.”
The once-daily oral medication was approved based on two trials. One trial, MOMENTUM, showed statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in anemic patients treated with momelotinib versus danazol.
An anemic subset of the SIMPLIFY-1 trial showed comparable spleen volume reduction versus ruxolitinib but a numerically lower symptom response rate.
The most common momelotinib adverse reactions in trials were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
A version of this article appeared on Medscape.com.
Momelotinib is the fourth JAK inhibitor to be approved by the agency for myelofibrosis but the only one indicated for patients with hemoglobin levels below 10 g/dL.
It’s an important development because, while JAK inhibitors are standard treatment for myelofibrosis, those previously approved for the uncommon blood cancer can cause cytopenia, particularly anemia, which, ironically, is also a hallmark of myelofibrosis itself.
This issue makes using JAK inhibitors for myelofibrosis challenging, according to Anthony Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta, who spoke on the topic recently at the annual meeting of the Society of Hematologic Oncology in Houston. “Momelotinib is an important emerging agent for these more anemic patients.” Momelotinib has a spleen response comparable with ruxolitinib – the first JAK inhibitor approved for myelofibrosis in the United States – and significantly higher rates of transfusion independence, although lower rates of symptom control, he said.
In GSK’s press release, hematologist/oncologist Ruben Mesa, MD, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, N.C., said that, “with momelotinib, we have the potential to establish a new standard of care for myelofibrosis patients with anemia.”
Momelotinib’s specific indication is for “the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia.”
The once-daily oral medication was approved based on two trials. One trial, MOMENTUM, showed statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in anemic patients treated with momelotinib versus danazol.
An anemic subset of the SIMPLIFY-1 trial showed comparable spleen volume reduction versus ruxolitinib but a numerically lower symptom response rate.
The most common momelotinib adverse reactions in trials were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
A version of this article appeared on Medscape.com.
Using JAK inhibitors for myelofibrosis
“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”
Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.
Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.
A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.
JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”
He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”
Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 109/L.
“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”
One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.
Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.
Pacritinib is approved specifically for patients with platelet counts below 50 x 109/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.
“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.
Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.
There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.
Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.
“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.
No disclosure information was reported.
“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”
Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.
Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.
A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.
JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”
He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”
Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 109/L.
“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”
One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.
Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.
Pacritinib is approved specifically for patients with platelet counts below 50 x 109/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.
“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.
Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.
There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.
Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.
“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.
No disclosure information was reported.
“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”
Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.
Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.
A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.
JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”
He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”
Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 109/L.
“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”
One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.
Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.
Pacritinib is approved specifically for patients with platelet counts below 50 x 109/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.
“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.
Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.
There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.
Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.
“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.
No disclosure information was reported.
FROM SOHO 2023
CHP/CCUS: Low blood cancer risk for most patients
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
FROM SOHO 2023
Drugmakers are abandoning cheap generics, and now U.S. cancer patients can’t get meds
On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.
Their decisions are likely to result in preventable deaths.
Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.
The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.
But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?
“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”
“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.
“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”
The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.
Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.
“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”
Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.
At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.
On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.
She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”
Doses remained at 80%, she said. Things hadn’t changed 10 days later.
Generics manufacturers are pulling out
The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.
As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.
The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.
Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.
The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.
Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.
Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”
Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.
“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
Should government step in?
Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.
As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.
Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”
More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.
“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.
Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.
In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.
“It would almost literally be a drop in the bucket.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.
Their decisions are likely to result in preventable deaths.
Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.
The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.
But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?
“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”
“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.
“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”
The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.
Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.
“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”
Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.
At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.
On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.
She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”
Doses remained at 80%, she said. Things hadn’t changed 10 days later.
Generics manufacturers are pulling out
The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.
As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.
The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.
Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.
The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.
Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.
Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”
Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.
“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
Should government step in?
Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.
As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.
Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”
More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.
“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.
Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.
In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.
“It would almost literally be a drop in the bucket.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.
Their decisions are likely to result in preventable deaths.
Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.
The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.
But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?
“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”
“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.
“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”
The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.
Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.
“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”
Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.
At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.
On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.
She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”
Doses remained at 80%, she said. Things hadn’t changed 10 days later.
Generics manufacturers are pulling out
The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.
As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.
The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.
Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.
The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.
Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.
Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”
Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.
“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
Should government step in?
Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.
As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.
Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”
More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.
“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.
Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.
In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.
“It would almost literally be a drop in the bucket.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.