User login
Hematocrit improvement with SGLT2 inhibitor: Not just a diuretic effect?
BOSTON – The SGLT2 inhibitor dapagliflozin may increase red blood cell production by suppressing plasma levels of hepcidin, a proinflammatory inhibitor of iron transport, according to results of a randomized study.
This reduction in hepcidin provides a new mechanistic explanation for the improvement in hematocrit seen with SGLT2 inhibitor treatment and suggests a role for use of these drugs beyond their current indications, according to researcher Husam A. Ghanim, PhD, of the State University of New York at Buffalo.
To see whether there were other mechanisms involved beyond hemoconcentration caused by diuretic effects of the drugs, Dr. Ghanim and his colleagues investigated the possibility that dapagliflozin might suppress concentrations of hepcidin concentrations, thereby increasing erythropoiesis.
Their study included 22 patients with type 2 diabetes and normal renal function randomized to dapagliflozin 10 mg daily or placebo for 12 weeks.
They found that the plasma concentration of hepcidin fell significantly over that time period, from 265 to 215 ng/mL in dapagliflozin-treated patients. They also saw significant decreases in hemoglobin A1c, hemoglobin concentration, and hematocrit, as well as an increase in transferrin, the major transporter of iron in the circulation, over 12 weeks.
No such significant changes in those measures were seen in the placebo group, Dr. Ghanim said.
There was a modest but nonsignificant increase in erythropoietin concentrations in the dapagliflozin-treated group, according to the researcher.
Circulating ferritin also fell by about 40% over the course of the study. “Circulating ferritin doesn’t have a clear indication or implication on iron transport,” Dr. Ghanim said. “However, it gets secreted from macrophages and from the liver, and it gets used as a marker for inflammation, and it’s also used as a marker of liver function. So a reduction in ferritin levels may have some clinical implication to what’s going on in the liver.”
On the basis of these findings, it appears that SGLT2 inhibition might increase hematocrit via anti-inflammatory effects and increased erythropoiesis, Dr. Ghanim said.
The increase in oxygenated blood available to tissues might contribute to the beneficial effects of SGLT2 inhibitors on cardiovascular disease, he added.
Also, it’s possible that SGLT2 inhibitors could have a “major impact” on the liver since hepcidin and ferritin are secreted mainly by the liver: “This could also lead us to think that it is possible that we could use SGLT2 inhibitors in conditions of liver inflammation like nonalcoholic steatohepatitis and fatty liver disease,” Dr. Ghanim said in his presentation. “These are future ideas we could explore, based on our data.”
Dr. Ghanim had no disclosures to report.
SOURCE: Ghanim HA et al. AACE 2018, Abstract 228.
BOSTON – The SGLT2 inhibitor dapagliflozin may increase red blood cell production by suppressing plasma levels of hepcidin, a proinflammatory inhibitor of iron transport, according to results of a randomized study.
This reduction in hepcidin provides a new mechanistic explanation for the improvement in hematocrit seen with SGLT2 inhibitor treatment and suggests a role for use of these drugs beyond their current indications, according to researcher Husam A. Ghanim, PhD, of the State University of New York at Buffalo.
To see whether there were other mechanisms involved beyond hemoconcentration caused by diuretic effects of the drugs, Dr. Ghanim and his colleagues investigated the possibility that dapagliflozin might suppress concentrations of hepcidin concentrations, thereby increasing erythropoiesis.
Their study included 22 patients with type 2 diabetes and normal renal function randomized to dapagliflozin 10 mg daily or placebo for 12 weeks.
They found that the plasma concentration of hepcidin fell significantly over that time period, from 265 to 215 ng/mL in dapagliflozin-treated patients. They also saw significant decreases in hemoglobin A1c, hemoglobin concentration, and hematocrit, as well as an increase in transferrin, the major transporter of iron in the circulation, over 12 weeks.
No such significant changes in those measures were seen in the placebo group, Dr. Ghanim said.
There was a modest but nonsignificant increase in erythropoietin concentrations in the dapagliflozin-treated group, according to the researcher.
Circulating ferritin also fell by about 40% over the course of the study. “Circulating ferritin doesn’t have a clear indication or implication on iron transport,” Dr. Ghanim said. “However, it gets secreted from macrophages and from the liver, and it gets used as a marker for inflammation, and it’s also used as a marker of liver function. So a reduction in ferritin levels may have some clinical implication to what’s going on in the liver.”
On the basis of these findings, it appears that SGLT2 inhibition might increase hematocrit via anti-inflammatory effects and increased erythropoiesis, Dr. Ghanim said.
The increase in oxygenated blood available to tissues might contribute to the beneficial effects of SGLT2 inhibitors on cardiovascular disease, he added.
Also, it’s possible that SGLT2 inhibitors could have a “major impact” on the liver since hepcidin and ferritin are secreted mainly by the liver: “This could also lead us to think that it is possible that we could use SGLT2 inhibitors in conditions of liver inflammation like nonalcoholic steatohepatitis and fatty liver disease,” Dr. Ghanim said in his presentation. “These are future ideas we could explore, based on our data.”
Dr. Ghanim had no disclosures to report.
SOURCE: Ghanim HA et al. AACE 2018, Abstract 228.
BOSTON – The SGLT2 inhibitor dapagliflozin may increase red blood cell production by suppressing plasma levels of hepcidin, a proinflammatory inhibitor of iron transport, according to results of a randomized study.
This reduction in hepcidin provides a new mechanistic explanation for the improvement in hematocrit seen with SGLT2 inhibitor treatment and suggests a role for use of these drugs beyond their current indications, according to researcher Husam A. Ghanim, PhD, of the State University of New York at Buffalo.
To see whether there were other mechanisms involved beyond hemoconcentration caused by diuretic effects of the drugs, Dr. Ghanim and his colleagues investigated the possibility that dapagliflozin might suppress concentrations of hepcidin concentrations, thereby increasing erythropoiesis.
Their study included 22 patients with type 2 diabetes and normal renal function randomized to dapagliflozin 10 mg daily or placebo for 12 weeks.
They found that the plasma concentration of hepcidin fell significantly over that time period, from 265 to 215 ng/mL in dapagliflozin-treated patients. They also saw significant decreases in hemoglobin A1c, hemoglobin concentration, and hematocrit, as well as an increase in transferrin, the major transporter of iron in the circulation, over 12 weeks.
No such significant changes in those measures were seen in the placebo group, Dr. Ghanim said.
There was a modest but nonsignificant increase in erythropoietin concentrations in the dapagliflozin-treated group, according to the researcher.
Circulating ferritin also fell by about 40% over the course of the study. “Circulating ferritin doesn’t have a clear indication or implication on iron transport,” Dr. Ghanim said. “However, it gets secreted from macrophages and from the liver, and it gets used as a marker for inflammation, and it’s also used as a marker of liver function. So a reduction in ferritin levels may have some clinical implication to what’s going on in the liver.”
On the basis of these findings, it appears that SGLT2 inhibition might increase hematocrit via anti-inflammatory effects and increased erythropoiesis, Dr. Ghanim said.
The increase in oxygenated blood available to tissues might contribute to the beneficial effects of SGLT2 inhibitors on cardiovascular disease, he added.
Also, it’s possible that SGLT2 inhibitors could have a “major impact” on the liver since hepcidin and ferritin are secreted mainly by the liver: “This could also lead us to think that it is possible that we could use SGLT2 inhibitors in conditions of liver inflammation like nonalcoholic steatohepatitis and fatty liver disease,” Dr. Ghanim said in his presentation. “These are future ideas we could explore, based on our data.”
Dr. Ghanim had no disclosures to report.
SOURCE: Ghanim HA et al. AACE 2018, Abstract 228.
REPORTING FROM AACE 2018
Key clinical point: The SGLT2 inhibitor dapagliflozin suppressed hepcidin, a proinflammatory inhibitor of iron transport.
Major finding: Hepcidin plasma concentration fell from 265 to 215 ng/mL (P < 0.05) in dapagliflozin-treated patients.
Study details: A study of 22 patients with type 2 diabetes randomized to either dapagliflozin 10 mg daily or placebo for 12 weeks.
Disclosures: Dr. Ghanim had no disclosures related to the presentation.
Source: Ghanim HA et al. AACE 2018, Abstract 228.
FDA approves first epoetin alfa biosimilar
The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).
Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.
Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.
As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.
The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.
The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.
This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.
The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).
Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.
Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.
As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.
The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.
The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.
This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.
The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).
Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.
Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.
As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.
The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.
The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.
This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.
FDA approves epoetin alfa biosimilar to treat anemia
, a treatment for anemia brought on by chronic kidney disease, chemotherapy, or use of zidovudine.
The biosimilar product is also approved to reduce the chance of red blood cell transfusion before and after surgery.
FDA’s approval, issued on May 15, is based on review of structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other safety and effectiveness information showing that the epoetin alfa-epbx is biosimilar to the reference product epoetin alfa. By approving epoetin alfa-epbx as a biosimilar, the FDA is saying that there are “no clinically meaningful differences in safety, purity, and potency” from epoetin alfa.
The agency’s approval comes almost a year after the Oncologic Drugs Advisory Committee voted 14-1 to support approval of the biosimilar. The FDA had rejected the application in 2017, citing manufacturing issues at a facility in Kansas, before ultimately approving the product in 2018.
The biosimilar product must be dispensed with a patient Medication Guide with information about uses and risks and carries a boxed warning about an increased risk of death, heart problems, stroke, and tumor growth or recurrence.
The biosimilar product is marketed by Hospira Inc., a Pfizer company.
, a treatment for anemia brought on by chronic kidney disease, chemotherapy, or use of zidovudine.
The biosimilar product is also approved to reduce the chance of red blood cell transfusion before and after surgery.
FDA’s approval, issued on May 15, is based on review of structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other safety and effectiveness information showing that the epoetin alfa-epbx is biosimilar to the reference product epoetin alfa. By approving epoetin alfa-epbx as a biosimilar, the FDA is saying that there are “no clinically meaningful differences in safety, purity, and potency” from epoetin alfa.
The agency’s approval comes almost a year after the Oncologic Drugs Advisory Committee voted 14-1 to support approval of the biosimilar. The FDA had rejected the application in 2017, citing manufacturing issues at a facility in Kansas, before ultimately approving the product in 2018.
The biosimilar product must be dispensed with a patient Medication Guide with information about uses and risks and carries a boxed warning about an increased risk of death, heart problems, stroke, and tumor growth or recurrence.
The biosimilar product is marketed by Hospira Inc., a Pfizer company.
, a treatment for anemia brought on by chronic kidney disease, chemotherapy, or use of zidovudine.
The biosimilar product is also approved to reduce the chance of red blood cell transfusion before and after surgery.
FDA’s approval, issued on May 15, is based on review of structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other safety and effectiveness information showing that the epoetin alfa-epbx is biosimilar to the reference product epoetin alfa. By approving epoetin alfa-epbx as a biosimilar, the FDA is saying that there are “no clinically meaningful differences in safety, purity, and potency” from epoetin alfa.
The agency’s approval comes almost a year after the Oncologic Drugs Advisory Committee voted 14-1 to support approval of the biosimilar. The FDA had rejected the application in 2017, citing manufacturing issues at a facility in Kansas, before ultimately approving the product in 2018.
The biosimilar product must be dispensed with a patient Medication Guide with information about uses and risks and carries a boxed warning about an increased risk of death, heart problems, stroke, and tumor growth or recurrence.
The biosimilar product is marketed by Hospira Inc., a Pfizer company.
IV superior to oral treatment for iron deficiency during pregnancy
AUSTIN, TEX. – Utilizing intravenous treatment for iron deficiency in anemic pregnant women was more efficacious than oral iron supplements, according to a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
With 42% of pregnancies worldwide affected by anemia, according to the World Health Organization, improving treatment beyond the standard oral treatment could have a large effect on decreasing pregnancy complications.
“Women with bariatric surgery and inflammatory bowel disease are at higher risk of failure,” said Shravya Govindappagari, MD, a gynecologist affiliated with New York–Presbyterian Hospital. “Intravenous iron overcomes the limited intestinal absorption of oral formulations, and may increase iron stores more quickly.”
Dr. Govindappagari and her colleagues conducted a meta-analysis of 11 randomly controlled trials published between 2002 and 2017 to uncover the possible benefits of intravenous iron over oral treatment.
Studies were conducted in India, Egypt, France, and Turkey, with one additional multicenter study that gathered patients from seven different countries. Participants were given iron sucrose, ferric carboxymaltose, or low molecular weight iron dextran, according to Dr. Govindappagari.
In an overall assessment of subjects who achieved target hemoglobin levels, patients receiving intravenous iron were 2.66 times more likely to reach target levels than those given oral treatment (P less than .001). After 4 weeks of treatment, patients in the intravenous groups had a mean hemoglobin increase of 0.84 g/dl higher than those in the oral group (P less than .001).
Some clinicians may be wary about switching treatment modality from oral to intravenous; however, Dr. Govindappagari and fellow investigators found those taking oral treatment were 35% more likely to experience adverse effects than those receiving intravenous treatment.
While the analysis, according to Dr. Govindappagari, has merit, she and her team did not have access to relevant blinded, randomly controlled trials, which may have affected the findings. Maternal and neonatal outcomes were also not included in any of the studies analyzed, nor was a cost analysis of the financial burden of switching from oral to intravenous treatment.
Despite these limitations, Dr. Govindappagari and her colleagues assert the use of intravenous iron could have a significant effect on this problem.
“Intravenous iron compared to oral iron has a higher number reach target, a greater increase in hemoglobin, and has fewer side effects,” Dr. Govindappagari said to attendees. “This could be particularly useful in women in labor, during the third trimester, and women who are iron deficient and are at risk for postpartum hemorrhage.”
Dr. Govindappagari and her colleagues reported no relevant financial disclosures.
SOURCE: Govindappagari S et al. ACOG 2018, Abstract 10OP.
AUSTIN, TEX. – Utilizing intravenous treatment for iron deficiency in anemic pregnant women was more efficacious than oral iron supplements, according to a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
With 42% of pregnancies worldwide affected by anemia, according to the World Health Organization, improving treatment beyond the standard oral treatment could have a large effect on decreasing pregnancy complications.
“Women with bariatric surgery and inflammatory bowel disease are at higher risk of failure,” said Shravya Govindappagari, MD, a gynecologist affiliated with New York–Presbyterian Hospital. “Intravenous iron overcomes the limited intestinal absorption of oral formulations, and may increase iron stores more quickly.”
Dr. Govindappagari and her colleagues conducted a meta-analysis of 11 randomly controlled trials published between 2002 and 2017 to uncover the possible benefits of intravenous iron over oral treatment.
Studies were conducted in India, Egypt, France, and Turkey, with one additional multicenter study that gathered patients from seven different countries. Participants were given iron sucrose, ferric carboxymaltose, or low molecular weight iron dextran, according to Dr. Govindappagari.
In an overall assessment of subjects who achieved target hemoglobin levels, patients receiving intravenous iron were 2.66 times more likely to reach target levels than those given oral treatment (P less than .001). After 4 weeks of treatment, patients in the intravenous groups had a mean hemoglobin increase of 0.84 g/dl higher than those in the oral group (P less than .001).
Some clinicians may be wary about switching treatment modality from oral to intravenous; however, Dr. Govindappagari and fellow investigators found those taking oral treatment were 35% more likely to experience adverse effects than those receiving intravenous treatment.
While the analysis, according to Dr. Govindappagari, has merit, she and her team did not have access to relevant blinded, randomly controlled trials, which may have affected the findings. Maternal and neonatal outcomes were also not included in any of the studies analyzed, nor was a cost analysis of the financial burden of switching from oral to intravenous treatment.
Despite these limitations, Dr. Govindappagari and her colleagues assert the use of intravenous iron could have a significant effect on this problem.
“Intravenous iron compared to oral iron has a higher number reach target, a greater increase in hemoglobin, and has fewer side effects,” Dr. Govindappagari said to attendees. “This could be particularly useful in women in labor, during the third trimester, and women who are iron deficient and are at risk for postpartum hemorrhage.”
Dr. Govindappagari and her colleagues reported no relevant financial disclosures.
SOURCE: Govindappagari S et al. ACOG 2018, Abstract 10OP.
AUSTIN, TEX. – Utilizing intravenous treatment for iron deficiency in anemic pregnant women was more efficacious than oral iron supplements, according to a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
With 42% of pregnancies worldwide affected by anemia, according to the World Health Organization, improving treatment beyond the standard oral treatment could have a large effect on decreasing pregnancy complications.
“Women with bariatric surgery and inflammatory bowel disease are at higher risk of failure,” said Shravya Govindappagari, MD, a gynecologist affiliated with New York–Presbyterian Hospital. “Intravenous iron overcomes the limited intestinal absorption of oral formulations, and may increase iron stores more quickly.”
Dr. Govindappagari and her colleagues conducted a meta-analysis of 11 randomly controlled trials published between 2002 and 2017 to uncover the possible benefits of intravenous iron over oral treatment.
Studies were conducted in India, Egypt, France, and Turkey, with one additional multicenter study that gathered patients from seven different countries. Participants were given iron sucrose, ferric carboxymaltose, or low molecular weight iron dextran, according to Dr. Govindappagari.
In an overall assessment of subjects who achieved target hemoglobin levels, patients receiving intravenous iron were 2.66 times more likely to reach target levels than those given oral treatment (P less than .001). After 4 weeks of treatment, patients in the intravenous groups had a mean hemoglobin increase of 0.84 g/dl higher than those in the oral group (P less than .001).
Some clinicians may be wary about switching treatment modality from oral to intravenous; however, Dr. Govindappagari and fellow investigators found those taking oral treatment were 35% more likely to experience adverse effects than those receiving intravenous treatment.
While the analysis, according to Dr. Govindappagari, has merit, she and her team did not have access to relevant blinded, randomly controlled trials, which may have affected the findings. Maternal and neonatal outcomes were also not included in any of the studies analyzed, nor was a cost analysis of the financial burden of switching from oral to intravenous treatment.
Despite these limitations, Dr. Govindappagari and her colleagues assert the use of intravenous iron could have a significant effect on this problem.
“Intravenous iron compared to oral iron has a higher number reach target, a greater increase in hemoglobin, and has fewer side effects,” Dr. Govindappagari said to attendees. “This could be particularly useful in women in labor, during the third trimester, and women who are iron deficient and are at risk for postpartum hemorrhage.”
Dr. Govindappagari and her colleagues reported no relevant financial disclosures.
SOURCE: Govindappagari S et al. ACOG 2018, Abstract 10OP.
REPORTING FROM ACOG 2018
Key clinical point: Intravenous iron treatment is better for pregnant women with anemia.
Major finding: Hemoglobin levels in women with intravenous iron increased by 1.2 g/dl more than in those using oral supplements after 4 weeks (P less than .001).
Data source: A meta-analysis of 11 randomized, controlled trials comparing intravenous with oral iron treatment.
Disclosures: Dr. Govindappagari and her colleagues reported no relevant financial disclosures.
Source: Govindappagari S et al. ACOG 2018, Abstract 10OP.
VIDEO: Anemia more than doubles risk of postpartum depression
AUSTIN, TEX. – The risk of depression was more than doubled in women who were anemic during pregnancy, according to a recent retrospective cohort study of nearly 1,000 women. Among patients who had anemia at any point, the relative risk of screening positive for postpartum depression was 2.25 (95% confidence interval, 1.22-4.16).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This was an unexpected finding,” said Shannon Sutherland, MD, of the University of Connecticut, Farmington, in an interview after she presented the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Maternal suicide exceeds hemorrhage and hypertensive disease as a cause of U.S. maternal mortality,” wrote Dr. Sutherland and her collaborators in the poster accompanying the presentation. And anemia is common: “Anemia in pregnancy can be as high as 27.4% in low-income minority pregnant women in the third trimester,” they wrote.
“If we can find something like this that affects depression, and screen for it and correct for it, we can make a real big difference in patients’ lives,” said Dr. Sutherland in a video interview. “Screening for anemia ... is such a simple thing for us to do, and I also think it’s very easy for us to correct, and very cheap for us to correct.”
The 922 study participants were at least 16 years old and receiving postpartum care at an outpatient women’s health clinic. Patients who had diseases that disrupted iron metabolism or were tobacco users, and those on antidepressants, anxiolytics, or antipsychotics were excluded from the study. Other exclusion criteria included anemia that required transfusion, and intrauterine fetal demise or neonatal mortality.
To assess depression, Dr. Sutherland and her colleagues administered the Edinburgh Postnatal Depression Scale at routine postpartum visits. Dr. Sutherland and her coinvestigators calculated the numbers of respondents who fell above and below the cutoff for potential depression on the 10-item self-report scale. They then looked at the proportion of women who scored positive for depression among those who were, and those who were not, anemic.
Possible depression was indicated by depression scale scores of 9.2% of participants, while three quarters (75.2%) were anemic either during pregnancy or in the immediate postpartum period. Among anemic patients, 10.8% screened positive for depression, while 4.8% of those without anemia met positive screening criteria for postpartum depression (P = .007).
Dr. Sutherland and her collaborators noted that fewer women in their cohort had postpartum depression than the national average of 19%. They may have missed some patients who would later develop depression since the screening occurred at the first postpartum visit; also, “it is possible that women deeply affected by [postpartum depression] may have been lost to follow-up,” they wrote.
Participants had a mean age of about 26 years, and body mass index was slightly higher for those with anemia than without (mean, 32.2 vs 31.2 kg/m2; P = .025).
Postpartum depression was not associated with marital status, substance use, ethnicity, parity, or the occurrence of postpartum hemorrhage, in the investigators’ analysis.
Dr. Sutherland said that, in their analysis, she and her coinvestigators did not find an association between degree of anemia and the likelihood, or severity, of postpartum depression. However, they did find that anemia of any degree in the immediate peripartum period was most strongly associated with postpartum depression.
Though the exact mechanism of the anemia-depression link isn’t known, the fatigue associated with anemia may help predispose women to postpartum depression, said Dr. Sutherland. Also, she said, “iron can make a difference in synthesizing neurotransmitters” such as serotonin, “so it may follow that you might have some depressive symptoms.”
“The next step after this study, which was a launching point, is to see if we correct the degree of anemia and bring them to normal levels, if that can help decrease the risk of postpartum depression,” said Dr. Sutherland.
Dr. Sutherland and her coinvestigators reported that they had no relevant financial disclosures.
SOURCE: Sutherland S et al. ACOG 2018. Abstract 35C.
AUSTIN, TEX. – The risk of depression was more than doubled in women who were anemic during pregnancy, according to a recent retrospective cohort study of nearly 1,000 women. Among patients who had anemia at any point, the relative risk of screening positive for postpartum depression was 2.25 (95% confidence interval, 1.22-4.16).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This was an unexpected finding,” said Shannon Sutherland, MD, of the University of Connecticut, Farmington, in an interview after she presented the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Maternal suicide exceeds hemorrhage and hypertensive disease as a cause of U.S. maternal mortality,” wrote Dr. Sutherland and her collaborators in the poster accompanying the presentation. And anemia is common: “Anemia in pregnancy can be as high as 27.4% in low-income minority pregnant women in the third trimester,” they wrote.
“If we can find something like this that affects depression, and screen for it and correct for it, we can make a real big difference in patients’ lives,” said Dr. Sutherland in a video interview. “Screening for anemia ... is such a simple thing for us to do, and I also think it’s very easy for us to correct, and very cheap for us to correct.”
The 922 study participants were at least 16 years old and receiving postpartum care at an outpatient women’s health clinic. Patients who had diseases that disrupted iron metabolism or were tobacco users, and those on antidepressants, anxiolytics, or antipsychotics were excluded from the study. Other exclusion criteria included anemia that required transfusion, and intrauterine fetal demise or neonatal mortality.
To assess depression, Dr. Sutherland and her colleagues administered the Edinburgh Postnatal Depression Scale at routine postpartum visits. Dr. Sutherland and her coinvestigators calculated the numbers of respondents who fell above and below the cutoff for potential depression on the 10-item self-report scale. They then looked at the proportion of women who scored positive for depression among those who were, and those who were not, anemic.
Possible depression was indicated by depression scale scores of 9.2% of participants, while three quarters (75.2%) were anemic either during pregnancy or in the immediate postpartum period. Among anemic patients, 10.8% screened positive for depression, while 4.8% of those without anemia met positive screening criteria for postpartum depression (P = .007).
Dr. Sutherland and her collaborators noted that fewer women in their cohort had postpartum depression than the national average of 19%. They may have missed some patients who would later develop depression since the screening occurred at the first postpartum visit; also, “it is possible that women deeply affected by [postpartum depression] may have been lost to follow-up,” they wrote.
Participants had a mean age of about 26 years, and body mass index was slightly higher for those with anemia than without (mean, 32.2 vs 31.2 kg/m2; P = .025).
Postpartum depression was not associated with marital status, substance use, ethnicity, parity, or the occurrence of postpartum hemorrhage, in the investigators’ analysis.
Dr. Sutherland said that, in their analysis, she and her coinvestigators did not find an association between degree of anemia and the likelihood, or severity, of postpartum depression. However, they did find that anemia of any degree in the immediate peripartum period was most strongly associated with postpartum depression.
Though the exact mechanism of the anemia-depression link isn’t known, the fatigue associated with anemia may help predispose women to postpartum depression, said Dr. Sutherland. Also, she said, “iron can make a difference in synthesizing neurotransmitters” such as serotonin, “so it may follow that you might have some depressive symptoms.”
“The next step after this study, which was a launching point, is to see if we correct the degree of anemia and bring them to normal levels, if that can help decrease the risk of postpartum depression,” said Dr. Sutherland.
Dr. Sutherland and her coinvestigators reported that they had no relevant financial disclosures.
SOURCE: Sutherland S et al. ACOG 2018. Abstract 35C.
AUSTIN, TEX. – The risk of depression was more than doubled in women who were anemic during pregnancy, according to a recent retrospective cohort study of nearly 1,000 women. Among patients who had anemia at any point, the relative risk of screening positive for postpartum depression was 2.25 (95% confidence interval, 1.22-4.16).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This was an unexpected finding,” said Shannon Sutherland, MD, of the University of Connecticut, Farmington, in an interview after she presented the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Maternal suicide exceeds hemorrhage and hypertensive disease as a cause of U.S. maternal mortality,” wrote Dr. Sutherland and her collaborators in the poster accompanying the presentation. And anemia is common: “Anemia in pregnancy can be as high as 27.4% in low-income minority pregnant women in the third trimester,” they wrote.
“If we can find something like this that affects depression, and screen for it and correct for it, we can make a real big difference in patients’ lives,” said Dr. Sutherland in a video interview. “Screening for anemia ... is such a simple thing for us to do, and I also think it’s very easy for us to correct, and very cheap for us to correct.”
The 922 study participants were at least 16 years old and receiving postpartum care at an outpatient women’s health clinic. Patients who had diseases that disrupted iron metabolism or were tobacco users, and those on antidepressants, anxiolytics, or antipsychotics were excluded from the study. Other exclusion criteria included anemia that required transfusion, and intrauterine fetal demise or neonatal mortality.
To assess depression, Dr. Sutherland and her colleagues administered the Edinburgh Postnatal Depression Scale at routine postpartum visits. Dr. Sutherland and her coinvestigators calculated the numbers of respondents who fell above and below the cutoff for potential depression on the 10-item self-report scale. They then looked at the proportion of women who scored positive for depression among those who were, and those who were not, anemic.
Possible depression was indicated by depression scale scores of 9.2% of participants, while three quarters (75.2%) were anemic either during pregnancy or in the immediate postpartum period. Among anemic patients, 10.8% screened positive for depression, while 4.8% of those without anemia met positive screening criteria for postpartum depression (P = .007).
Dr. Sutherland and her collaborators noted that fewer women in their cohort had postpartum depression than the national average of 19%. They may have missed some patients who would later develop depression since the screening occurred at the first postpartum visit; also, “it is possible that women deeply affected by [postpartum depression] may have been lost to follow-up,” they wrote.
Participants had a mean age of about 26 years, and body mass index was slightly higher for those with anemia than without (mean, 32.2 vs 31.2 kg/m2; P = .025).
Postpartum depression was not associated with marital status, substance use, ethnicity, parity, or the occurrence of postpartum hemorrhage, in the investigators’ analysis.
Dr. Sutherland said that, in their analysis, she and her coinvestigators did not find an association between degree of anemia and the likelihood, or severity, of postpartum depression. However, they did find that anemia of any degree in the immediate peripartum period was most strongly associated with postpartum depression.
Though the exact mechanism of the anemia-depression link isn’t known, the fatigue associated with anemia may help predispose women to postpartum depression, said Dr. Sutherland. Also, she said, “iron can make a difference in synthesizing neurotransmitters” such as serotonin, “so it may follow that you might have some depressive symptoms.”
“The next step after this study, which was a launching point, is to see if we correct the degree of anemia and bring them to normal levels, if that can help decrease the risk of postpartum depression,” said Dr. Sutherland.
Dr. Sutherland and her coinvestigators reported that they had no relevant financial disclosures.
SOURCE: Sutherland S et al. ACOG 2018. Abstract 35C.
REPORTING FROM ACOG 2018
Too few Michigan children with SCD receive pneumococcal, meningococcal vaccines
Substantial percentages of children with sickle cell disease are not receiving certain recommended vaccines on time or at all, found a study examining receipt of pneumococcal and meningococcal vaccines among children born in Michigan.
Although these children were more likely to be up-to-date on their pneumococcal vaccines than others their age without sickle cell disease (SCD), nearly one-third had not received all their pneumococcal vaccines by 36 months old. These children are at higher risk of meningococcal and invasive pneumococcal disease because they lack normal spleen function.
ACIP has recommended since February 2010 that all children receive the 13-valent pneumococcal conjugate vaccine (PCV13), which replaced the 7-valent pneumococcal conjugate vaccine (PCV7) that had been recommended since October 2000.
But ACIP also recommends that children with SCD receive two doses of the 23-valent polysaccharide vaccine (PPV23), starting at 2 years old. These children also should receive a PCV13 dose before age 18 years, even if they received the full PCV7 vaccine series.
“By directly including SCD status in a child’s immunization record, an immunization information system could use a specialized algorithm to indicate to healthcare providers which vaccines should be given to a patient with SCD, which may differ from a typical patient,” Dr. Wagner and his colleagues wrote in The Journal of Pediatrics.
“Educational campaigns targeted to parents of these children and their providers could also help advance the importance of vaccination, particularly as more vaccines enter the market, many of which may be highly recommended for children with SCD,” they said.
The researchers matched 1,022 children with SCD to 3,725 children without SCD based on age, sex, race, and zip code. The data was based on the Michigan Care Improvement Registry (MCIR), Michigan Vital Records live birth file, and the Michigan Newborn Screening Program for children born in the state between April 1, 1995, and January 1, 2014.
At age 36 months, 69% of children with SCD had been fully vaccinated with the pneumococcal conjugate vaccine series, compared with 45% of children without SCD. The meningococcal vaccine had been administered to 59% of children with SCD.
Children with SCD were more likely than those without the disease to be up-to-date on their pneumococcal vaccine(s) at 5, 7 and 16 months old.
Nevertheless, substantial percentages of children with SCD who received the complete series of the 7-valent pneumococcal conjugate vaccine had not received two other pneumococcal vaccines. Just over 29% were missing a dose of PCV13, 21.8% of children over 2 years old had not received any dose of PPV23, and 50.7% had not received a second dose of PPV23 by the age of 10 years.
The authors drew attention to the complexity of ACIP recommendations, however: ACIP released 7 recommendations a year, on average, between 2006 and 2015.
“Although providers have a responsibility to educate themselves on how best to protect children with high-risk conditions, these figures speak to the need for MCIR, the state’s immunization information system, to provide additional information on children, such as those who have sickle cell disease, who have special vaccination recommendations,” the authors wrote.
The authors reported no conflicts of interest. No external funding was noted.
SOURCE: Wagner AL et al. J Pediatr. J Pediatr. 2018 May;196:223-9.
This study is particularly valuable because of the “depth, breadth and completeness” of data from across an entire state, a control group that is socioeconomically matched, and a study that was done during a time when new, life-saving vaccines were licensed and recommended. The many changes in the recommendations because of new vaccines and new understanding of the best use of these vaccines make for a complex schedule, but we health care providers need to keep current and to educate parents so their children are protected against infectious diseases. For parents of children with sickle cell disease, the schedule is more complex and the need is greater because of their extreme vulnerability. Wagner et al. suggest that “a proactive electronic prompt to providers [and parents] for vaccines needed for children with special conditions [as exists for the general immunization schedule] is needed – and seems doable.”
Sarah S. Long, MD, is a professor of pediatrics at Drexel University, Philadelphia. She is an associate editor of the Journal of Pediatrics and the Red Book Report of the Committee on Infectious Diseases of the American Academy of Pediatrics. She reported no disclosures. This is a summary of her editorial accompanying the article by Wagner et al. (J. Pediatr. 2018;196:3).
This study is particularly valuable because of the “depth, breadth and completeness” of data from across an entire state, a control group that is socioeconomically matched, and a study that was done during a time when new, life-saving vaccines were licensed and recommended. The many changes in the recommendations because of new vaccines and new understanding of the best use of these vaccines make for a complex schedule, but we health care providers need to keep current and to educate parents so their children are protected against infectious diseases. For parents of children with sickle cell disease, the schedule is more complex and the need is greater because of their extreme vulnerability. Wagner et al. suggest that “a proactive electronic prompt to providers [and parents] for vaccines needed for children with special conditions [as exists for the general immunization schedule] is needed – and seems doable.”
Sarah S. Long, MD, is a professor of pediatrics at Drexel University, Philadelphia. She is an associate editor of the Journal of Pediatrics and the Red Book Report of the Committee on Infectious Diseases of the American Academy of Pediatrics. She reported no disclosures. This is a summary of her editorial accompanying the article by Wagner et al. (J. Pediatr. 2018;196:3).
This study is particularly valuable because of the “depth, breadth and completeness” of data from across an entire state, a control group that is socioeconomically matched, and a study that was done during a time when new, life-saving vaccines were licensed and recommended. The many changes in the recommendations because of new vaccines and new understanding of the best use of these vaccines make for a complex schedule, but we health care providers need to keep current and to educate parents so their children are protected against infectious diseases. For parents of children with sickle cell disease, the schedule is more complex and the need is greater because of their extreme vulnerability. Wagner et al. suggest that “a proactive electronic prompt to providers [and parents] for vaccines needed for children with special conditions [as exists for the general immunization schedule] is needed – and seems doable.”
Sarah S. Long, MD, is a professor of pediatrics at Drexel University, Philadelphia. She is an associate editor of the Journal of Pediatrics and the Red Book Report of the Committee on Infectious Diseases of the American Academy of Pediatrics. She reported no disclosures. This is a summary of her editorial accompanying the article by Wagner et al. (J. Pediatr. 2018;196:3).
Substantial percentages of children with sickle cell disease are not receiving certain recommended vaccines on time or at all, found a study examining receipt of pneumococcal and meningococcal vaccines among children born in Michigan.
Although these children were more likely to be up-to-date on their pneumococcal vaccines than others their age without sickle cell disease (SCD), nearly one-third had not received all their pneumococcal vaccines by 36 months old. These children are at higher risk of meningococcal and invasive pneumococcal disease because they lack normal spleen function.
ACIP has recommended since February 2010 that all children receive the 13-valent pneumococcal conjugate vaccine (PCV13), which replaced the 7-valent pneumococcal conjugate vaccine (PCV7) that had been recommended since October 2000.
But ACIP also recommends that children with SCD receive two doses of the 23-valent polysaccharide vaccine (PPV23), starting at 2 years old. These children also should receive a PCV13 dose before age 18 years, even if they received the full PCV7 vaccine series.
“By directly including SCD status in a child’s immunization record, an immunization information system could use a specialized algorithm to indicate to healthcare providers which vaccines should be given to a patient with SCD, which may differ from a typical patient,” Dr. Wagner and his colleagues wrote in The Journal of Pediatrics.
“Educational campaigns targeted to parents of these children and their providers could also help advance the importance of vaccination, particularly as more vaccines enter the market, many of which may be highly recommended for children with SCD,” they said.
The researchers matched 1,022 children with SCD to 3,725 children without SCD based on age, sex, race, and zip code. The data was based on the Michigan Care Improvement Registry (MCIR), Michigan Vital Records live birth file, and the Michigan Newborn Screening Program for children born in the state between April 1, 1995, and January 1, 2014.
At age 36 months, 69% of children with SCD had been fully vaccinated with the pneumococcal conjugate vaccine series, compared with 45% of children without SCD. The meningococcal vaccine had been administered to 59% of children with SCD.
Children with SCD were more likely than those without the disease to be up-to-date on their pneumococcal vaccine(s) at 5, 7 and 16 months old.
Nevertheless, substantial percentages of children with SCD who received the complete series of the 7-valent pneumococcal conjugate vaccine had not received two other pneumococcal vaccines. Just over 29% were missing a dose of PCV13, 21.8% of children over 2 years old had not received any dose of PPV23, and 50.7% had not received a second dose of PPV23 by the age of 10 years.
The authors drew attention to the complexity of ACIP recommendations, however: ACIP released 7 recommendations a year, on average, between 2006 and 2015.
“Although providers have a responsibility to educate themselves on how best to protect children with high-risk conditions, these figures speak to the need for MCIR, the state’s immunization information system, to provide additional information on children, such as those who have sickle cell disease, who have special vaccination recommendations,” the authors wrote.
The authors reported no conflicts of interest. No external funding was noted.
SOURCE: Wagner AL et al. J Pediatr. J Pediatr. 2018 May;196:223-9.
Substantial percentages of children with sickle cell disease are not receiving certain recommended vaccines on time or at all, found a study examining receipt of pneumococcal and meningococcal vaccines among children born in Michigan.
Although these children were more likely to be up-to-date on their pneumococcal vaccines than others their age without sickle cell disease (SCD), nearly one-third had not received all their pneumococcal vaccines by 36 months old. These children are at higher risk of meningococcal and invasive pneumococcal disease because they lack normal spleen function.
ACIP has recommended since February 2010 that all children receive the 13-valent pneumococcal conjugate vaccine (PCV13), which replaced the 7-valent pneumococcal conjugate vaccine (PCV7) that had been recommended since October 2000.
But ACIP also recommends that children with SCD receive two doses of the 23-valent polysaccharide vaccine (PPV23), starting at 2 years old. These children also should receive a PCV13 dose before age 18 years, even if they received the full PCV7 vaccine series.
“By directly including SCD status in a child’s immunization record, an immunization information system could use a specialized algorithm to indicate to healthcare providers which vaccines should be given to a patient with SCD, which may differ from a typical patient,” Dr. Wagner and his colleagues wrote in The Journal of Pediatrics.
“Educational campaigns targeted to parents of these children and their providers could also help advance the importance of vaccination, particularly as more vaccines enter the market, many of which may be highly recommended for children with SCD,” they said.
The researchers matched 1,022 children with SCD to 3,725 children without SCD based on age, sex, race, and zip code. The data was based on the Michigan Care Improvement Registry (MCIR), Michigan Vital Records live birth file, and the Michigan Newborn Screening Program for children born in the state between April 1, 1995, and January 1, 2014.
At age 36 months, 69% of children with SCD had been fully vaccinated with the pneumococcal conjugate vaccine series, compared with 45% of children without SCD. The meningococcal vaccine had been administered to 59% of children with SCD.
Children with SCD were more likely than those without the disease to be up-to-date on their pneumococcal vaccine(s) at 5, 7 and 16 months old.
Nevertheless, substantial percentages of children with SCD who received the complete series of the 7-valent pneumococcal conjugate vaccine had not received two other pneumococcal vaccines. Just over 29% were missing a dose of PCV13, 21.8% of children over 2 years old had not received any dose of PPV23, and 50.7% had not received a second dose of PPV23 by the age of 10 years.
The authors drew attention to the complexity of ACIP recommendations, however: ACIP released 7 recommendations a year, on average, between 2006 and 2015.
“Although providers have a responsibility to educate themselves on how best to protect children with high-risk conditions, these figures speak to the need for MCIR, the state’s immunization information system, to provide additional information on children, such as those who have sickle cell disease, who have special vaccination recommendations,” the authors wrote.
The authors reported no conflicts of interest. No external funding was noted.
SOURCE: Wagner AL et al. J Pediatr. J Pediatr. 2018 May;196:223-9.
Key clinical point: Too few children with sickle cell disease (SCD) are receiving Advisory Committee on Immunization Practices–recommended meningococcal and pneumococcal vaccines, including PCV13 and PPSV23.
Major finding:
Study details: The findings are based on a cohort study of children with and without SCD born in Michigan between April 1, 1995, and January 1, 2014.
Disclosures: The authors reported no conflicts of interest. No external funding was noted.
Source: Wagner AL et al. J Pediatr. 2018 May;196:223-9.
Haplo-HSCT regimen can cure SCD, team says
A haploidentical transplant regimen has led to long-term engraftment in adults with sickle cell disease (SCD), according to researchers.
Seven of 8 patients treated with this regimen were still alive at last follow-up, and 6 of them maintained engraftment.
Two patients developed graft-versus-host disease (GVHD). One of them had acute and chronic GVHD and died about 400 days after transplant. The other had acute GVHD that resolved with treatment.
Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues reported these results in Biology of Blood and Marrow Transplantation.
The researchers initially screened 50 adult SCD patients as candidates for haploidentical hematopoietic stem cell transplant (haplo-HSCT) between January 2014 and March 2017. Most patients were ineligible or declined the procedure.
Ultimately, 10 patients received a haplo-HSCT. Unfortunately, the first 2 patients failed to engraft. These patients had received conditioning with alemtuzumab and 3 Gy total body irradiation (TBI) as well as post-transplant cyclophosphamide.
Because of this failure, the researchers used the following regimen for the remaining 8 patients. It’s a modified version of the regimen described in Blood in 2012.
“We modified the transplant protocol by increasing the dose of radiation used before the transplant and by infusing growth factor-mobilized peripheral blood stem cells instead of bone marrow cells,” Dr Rondelli said. “These two modifications helped ensure the patient’s body could accept the healthy donor cells.”
Modified regimen
Patients received growth-factor-mobilized peripheral blood stem cells after conditioning with rabbit antithymocyte globulin (0.5 mg/kg on day -9, 2 mg/kg on day -8 and -7), cyclophosphamide (14.5 mg/kg on day -6 and -5), fludarabine (30 mg/m2 on day -6 to -2), and single-dose TBI (3 Gy on day -1).
For GVHD prophylaxis, patients received intravenous cyclophosphamide (50 mg/kg on day 3 and 4), oral mycophenolate mofetil (15 mg/kg 3 times daily from day 5 to 35), and sirolimus (from day 5 dosed for a target trough of 5 to 15 ng/mL). In patients who had T-cell chimerism greater than 50% at 1 year after HSCT and did not have signs of GVHD, sirolimus was tapered off over 3 months.
Patients stopped taking hydroxyurea on day -9. They received red blood cell exchange transfusion on day -10 (with the goal of getting hemoglobin S below 30%) and received platelet transfusions to maintain platelet counts greater than 50 x 109 cells/L.
Patients also received penicillin V (250 mg twice daily) in addition to standard antimicrobial prophylaxis.
Results
All 8 patients on the modified regimen engrafted. The median time to neutrophil engraftment was 22 days (range, 18 to 23 days). One patient experienced secondary graft failure on day 90.
Seven neutropenic patients with hemoglobin S less than 30% received G-CSF after transplant. They received a median of 7 doses (range, 3 to 14) at 5 μg/kg, starting at day 12 post-HSCT. One of these patients experienced mild bone pain in the lower extremities.
Two patients developed GVHD. At day 83, one patient developed acute or chronic GVHD involving the skin, liver, and eyes. Steroids and sirolimus improved eye and liver symptoms, but the patient died at home on day 407.
The other patient had grade 2, gastrointestinal, acute GVHD that resolved with steroid therapy.
Three patients had grade 2 or higher mucositis, and 2 had cytomegalovirus (CMV) reactivation without CMV infection.
Two patients had small subarachnoid hemorrhages. One of these patients had a history of multiple red blood cell antibodies, became refractory to platelet transfusions, and developed small subarachnoid hemorrhages day 10. The patient’s symptoms and brain imaging resolved after platelet counts were maintained above 50 x 109 cells/L with cross-matched platelets.
The second patient had a history of stroke, experienced a seizure when the platelet count was 68 x 109 cells/L, and was found to have a subarachnoid hemorrhage on day 12. Symptoms and imaging results improved once the patient began levetiracetam and platelet levels were maintained above 100 x 109 cells/L.
At a median follow-up of 17 months (range, 12 to 30), 7 of the 8 patients were still alive.
Six patients had maintained greater than 95% stable donor engraftment with improvements in their hemoglobin concentrations. Three of these patients have stopped immunosuppression, and 3 are being tapered off it.
“These patients are cured of sickle cell disease,” Dr Rondelli said. “The takeaway message is two-fold. First, this transplant protocol may cure many more adult patients with advanced sickle cell disease.”
“Second, despite the increasing safety of the transplant protocols and new compatibility of HLA half-matched donors, many sickle cell patients still face barriers to care. Of the patients we screened, only 20% underwent a transplant.”
Dr Rondelli noted that 20% of the patients screened could not undergo transplant because of insurance denial. Other patients were ineligible because they had high rates of donor-specific antigens, and still others declined transplant.
A haploidentical transplant regimen has led to long-term engraftment in adults with sickle cell disease (SCD), according to researchers.
Seven of 8 patients treated with this regimen were still alive at last follow-up, and 6 of them maintained engraftment.
Two patients developed graft-versus-host disease (GVHD). One of them had acute and chronic GVHD and died about 400 days after transplant. The other had acute GVHD that resolved with treatment.
Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues reported these results in Biology of Blood and Marrow Transplantation.
The researchers initially screened 50 adult SCD patients as candidates for haploidentical hematopoietic stem cell transplant (haplo-HSCT) between January 2014 and March 2017. Most patients were ineligible or declined the procedure.
Ultimately, 10 patients received a haplo-HSCT. Unfortunately, the first 2 patients failed to engraft. These patients had received conditioning with alemtuzumab and 3 Gy total body irradiation (TBI) as well as post-transplant cyclophosphamide.
Because of this failure, the researchers used the following regimen for the remaining 8 patients. It’s a modified version of the regimen described in Blood in 2012.
“We modified the transplant protocol by increasing the dose of radiation used before the transplant and by infusing growth factor-mobilized peripheral blood stem cells instead of bone marrow cells,” Dr Rondelli said. “These two modifications helped ensure the patient’s body could accept the healthy donor cells.”
Modified regimen
Patients received growth-factor-mobilized peripheral blood stem cells after conditioning with rabbit antithymocyte globulin (0.5 mg/kg on day -9, 2 mg/kg on day -8 and -7), cyclophosphamide (14.5 mg/kg on day -6 and -5), fludarabine (30 mg/m2 on day -6 to -2), and single-dose TBI (3 Gy on day -1).
For GVHD prophylaxis, patients received intravenous cyclophosphamide (50 mg/kg on day 3 and 4), oral mycophenolate mofetil (15 mg/kg 3 times daily from day 5 to 35), and sirolimus (from day 5 dosed for a target trough of 5 to 15 ng/mL). In patients who had T-cell chimerism greater than 50% at 1 year after HSCT and did not have signs of GVHD, sirolimus was tapered off over 3 months.
Patients stopped taking hydroxyurea on day -9. They received red blood cell exchange transfusion on day -10 (with the goal of getting hemoglobin S below 30%) and received platelet transfusions to maintain platelet counts greater than 50 x 109 cells/L.
Patients also received penicillin V (250 mg twice daily) in addition to standard antimicrobial prophylaxis.
Results
All 8 patients on the modified regimen engrafted. The median time to neutrophil engraftment was 22 days (range, 18 to 23 days). One patient experienced secondary graft failure on day 90.
Seven neutropenic patients with hemoglobin S less than 30% received G-CSF after transplant. They received a median of 7 doses (range, 3 to 14) at 5 μg/kg, starting at day 12 post-HSCT. One of these patients experienced mild bone pain in the lower extremities.
Two patients developed GVHD. At day 83, one patient developed acute or chronic GVHD involving the skin, liver, and eyes. Steroids and sirolimus improved eye and liver symptoms, but the patient died at home on day 407.
The other patient had grade 2, gastrointestinal, acute GVHD that resolved with steroid therapy.
Three patients had grade 2 or higher mucositis, and 2 had cytomegalovirus (CMV) reactivation without CMV infection.
Two patients had small subarachnoid hemorrhages. One of these patients had a history of multiple red blood cell antibodies, became refractory to platelet transfusions, and developed small subarachnoid hemorrhages day 10. The patient’s symptoms and brain imaging resolved after platelet counts were maintained above 50 x 109 cells/L with cross-matched platelets.
The second patient had a history of stroke, experienced a seizure when the platelet count was 68 x 109 cells/L, and was found to have a subarachnoid hemorrhage on day 12. Symptoms and imaging results improved once the patient began levetiracetam and platelet levels were maintained above 100 x 109 cells/L.
At a median follow-up of 17 months (range, 12 to 30), 7 of the 8 patients were still alive.
Six patients had maintained greater than 95% stable donor engraftment with improvements in their hemoglobin concentrations. Three of these patients have stopped immunosuppression, and 3 are being tapered off it.
“These patients are cured of sickle cell disease,” Dr Rondelli said. “The takeaway message is two-fold. First, this transplant protocol may cure many more adult patients with advanced sickle cell disease.”
“Second, despite the increasing safety of the transplant protocols and new compatibility of HLA half-matched donors, many sickle cell patients still face barriers to care. Of the patients we screened, only 20% underwent a transplant.”
Dr Rondelli noted that 20% of the patients screened could not undergo transplant because of insurance denial. Other patients were ineligible because they had high rates of donor-specific antigens, and still others declined transplant.
A haploidentical transplant regimen has led to long-term engraftment in adults with sickle cell disease (SCD), according to researchers.
Seven of 8 patients treated with this regimen were still alive at last follow-up, and 6 of them maintained engraftment.
Two patients developed graft-versus-host disease (GVHD). One of them had acute and chronic GVHD and died about 400 days after transplant. The other had acute GVHD that resolved with treatment.
Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues reported these results in Biology of Blood and Marrow Transplantation.
The researchers initially screened 50 adult SCD patients as candidates for haploidentical hematopoietic stem cell transplant (haplo-HSCT) between January 2014 and March 2017. Most patients were ineligible or declined the procedure.
Ultimately, 10 patients received a haplo-HSCT. Unfortunately, the first 2 patients failed to engraft. These patients had received conditioning with alemtuzumab and 3 Gy total body irradiation (TBI) as well as post-transplant cyclophosphamide.
Because of this failure, the researchers used the following regimen for the remaining 8 patients. It’s a modified version of the regimen described in Blood in 2012.
“We modified the transplant protocol by increasing the dose of radiation used before the transplant and by infusing growth factor-mobilized peripheral blood stem cells instead of bone marrow cells,” Dr Rondelli said. “These two modifications helped ensure the patient’s body could accept the healthy donor cells.”
Modified regimen
Patients received growth-factor-mobilized peripheral blood stem cells after conditioning with rabbit antithymocyte globulin (0.5 mg/kg on day -9, 2 mg/kg on day -8 and -7), cyclophosphamide (14.5 mg/kg on day -6 and -5), fludarabine (30 mg/m2 on day -6 to -2), and single-dose TBI (3 Gy on day -1).
For GVHD prophylaxis, patients received intravenous cyclophosphamide (50 mg/kg on day 3 and 4), oral mycophenolate mofetil (15 mg/kg 3 times daily from day 5 to 35), and sirolimus (from day 5 dosed for a target trough of 5 to 15 ng/mL). In patients who had T-cell chimerism greater than 50% at 1 year after HSCT and did not have signs of GVHD, sirolimus was tapered off over 3 months.
Patients stopped taking hydroxyurea on day -9. They received red blood cell exchange transfusion on day -10 (with the goal of getting hemoglobin S below 30%) and received platelet transfusions to maintain platelet counts greater than 50 x 109 cells/L.
Patients also received penicillin V (250 mg twice daily) in addition to standard antimicrobial prophylaxis.
Results
All 8 patients on the modified regimen engrafted. The median time to neutrophil engraftment was 22 days (range, 18 to 23 days). One patient experienced secondary graft failure on day 90.
Seven neutropenic patients with hemoglobin S less than 30% received G-CSF after transplant. They received a median of 7 doses (range, 3 to 14) at 5 μg/kg, starting at day 12 post-HSCT. One of these patients experienced mild bone pain in the lower extremities.
Two patients developed GVHD. At day 83, one patient developed acute or chronic GVHD involving the skin, liver, and eyes. Steroids and sirolimus improved eye and liver symptoms, but the patient died at home on day 407.
The other patient had grade 2, gastrointestinal, acute GVHD that resolved with steroid therapy.
Three patients had grade 2 or higher mucositis, and 2 had cytomegalovirus (CMV) reactivation without CMV infection.
Two patients had small subarachnoid hemorrhages. One of these patients had a history of multiple red blood cell antibodies, became refractory to platelet transfusions, and developed small subarachnoid hemorrhages day 10. The patient’s symptoms and brain imaging resolved after platelet counts were maintained above 50 x 109 cells/L with cross-matched platelets.
The second patient had a history of stroke, experienced a seizure when the platelet count was 68 x 109 cells/L, and was found to have a subarachnoid hemorrhage on day 12. Symptoms and imaging results improved once the patient began levetiracetam and platelet levels were maintained above 100 x 109 cells/L.
At a median follow-up of 17 months (range, 12 to 30), 7 of the 8 patients were still alive.
Six patients had maintained greater than 95% stable donor engraftment with improvements in their hemoglobin concentrations. Three of these patients have stopped immunosuppression, and 3 are being tapered off it.
“These patients are cured of sickle cell disease,” Dr Rondelli said. “The takeaway message is two-fold. First, this transplant protocol may cure many more adult patients with advanced sickle cell disease.”
“Second, despite the increasing safety of the transplant protocols and new compatibility of HLA half-matched donors, many sickle cell patients still face barriers to care. Of the patients we screened, only 20% underwent a transplant.”
Dr Rondelli noted that 20% of the patients screened could not undergo transplant because of insurance denial. Other patients were ineligible because they had high rates of donor-specific antigens, and still others declined transplant.
Gene therapy for thalassemia normalizes hemoglobin
Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.
Of 13 patients who did not have the most severe beta0/beta0 genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta0/beta0 genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.
At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.
“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.
Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.
Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.
There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.
In both studies, after mobilization, patients’ unmanipulated hematopoietic stem cells and progenitor cells were taken to a central processing facility, where CD34+ cells were enriched and then transduced with the lentiviral vector BB305, which encodes adult hemoglobin (HbA) with a T87Z amino acid substitution and thereby provides functioning Hb beta. Patients received the product via infusion after undergoing myeloablative conditioning with busulfan.
A total of 23 patients, 19 in the international study and 4 in the French study, went through mobilization and apheresis. One patient in the international study had apheresis failure, so a total of 22 patients received LentiGlobin, and all were followed for up to 2 years.
Patients were given the opportunity to participate in a follow-on open label study meant to continue for an additional 13 years after the initial 24-month period; 13 patients are currently enrolled in this long-term follow-up study.
When transfusion volume at baseline was assessed, patients in the international study were receiving a median annual red blood cell transfusion volume of 164 mL/kg per year, while the French study participants were receiving a median 182 mL/kg per year of red blood cell transfusion.
In both studies, blood HbAT87Q levels correlated with the vector copy numbers (R2, 0.75; P less than .001). Levels of HbAT87Q ranged from 3.4-10.0 g/dL.
“Other factors, such as age, genotype, and splenectomy status, did not appear to correlate with gene expression,” the researchers wrote.
An exploratory analysis looked at characteristics of patients who were able to stop transfusions after gene therapy. In this group, “the degree of hemolysis at first stabilized relative to pretransplantation levels and was fully corrected” in two patients by 36 months after treatment.
The researchers noted that the sponsor achieved “high-titer, large-scale, clinical-grade BB305 vector production and purification by ion-exchange chromatography” from a single site in the United States, which showed the feasibility of conducting this modality of gene therapy at scale.
The study was sponsored by bluebird bio, the National Institutes of Health, and by French national research organizations. Dr. Thompson reported research funding and fees from bluebird bio and other pharmaceutical companies.
SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93
Lentiviral vector hematopoietic stem cell (HSC) gene therapy represents a promising alternative to matched-sibling donor HSC transplants for treatment of beta thalassemia, with studies to date showing a safety profile that surpasses transplants from unrelated or alternative donors.
The prospect of a curative treatment raised by the work of Dr. Thompson and her colleagues also shows the feasibility of transfusion independence for beta0/betaE patients, who carry the most common beta thalassemia genotype, and a significant reduction in transfusions even for patients with the more severe beta0/beta0 genotype.
Beta thalassemia has greatest prevalence in North Africa, the Middle East, and Asia, where access to treatments is limited and patients’ prognoses are often grim. Gene therapy for beta thalassemia could thereby represent the first large-scale implementation of this intervention in developing countries.
Bringing HSC gene therapy to more patients will require not just the availability of autologous HSCs, but of high-quality vector and reliable, high-volume manufacturing of transduced cells.
Harnessing this still-evolving technology to bring a potentially curative treatment to patients in developing countries is an exciting, but challenging, frontier for physicians and researchers involved with gene therapy.
Alessandra Biffi, MD, is director of the gene therapy program at Dana Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, Boston. She serves on the board of directors of the American Society of Gene and Cell Therapy. These remarks were adapted from an accompanying editorial ( N Engl J Med. 2018;378[16]:1551-2 ).
Lentiviral vector hematopoietic stem cell (HSC) gene therapy represents a promising alternative to matched-sibling donor HSC transplants for treatment of beta thalassemia, with studies to date showing a safety profile that surpasses transplants from unrelated or alternative donors.
The prospect of a curative treatment raised by the work of Dr. Thompson and her colleagues also shows the feasibility of transfusion independence for beta0/betaE patients, who carry the most common beta thalassemia genotype, and a significant reduction in transfusions even for patients with the more severe beta0/beta0 genotype.
Beta thalassemia has greatest prevalence in North Africa, the Middle East, and Asia, where access to treatments is limited and patients’ prognoses are often grim. Gene therapy for beta thalassemia could thereby represent the first large-scale implementation of this intervention in developing countries.
Bringing HSC gene therapy to more patients will require not just the availability of autologous HSCs, but of high-quality vector and reliable, high-volume manufacturing of transduced cells.
Harnessing this still-evolving technology to bring a potentially curative treatment to patients in developing countries is an exciting, but challenging, frontier for physicians and researchers involved with gene therapy.
Alessandra Biffi, MD, is director of the gene therapy program at Dana Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, Boston. She serves on the board of directors of the American Society of Gene and Cell Therapy. These remarks were adapted from an accompanying editorial ( N Engl J Med. 2018;378[16]:1551-2 ).
Lentiviral vector hematopoietic stem cell (HSC) gene therapy represents a promising alternative to matched-sibling donor HSC transplants for treatment of beta thalassemia, with studies to date showing a safety profile that surpasses transplants from unrelated or alternative donors.
The prospect of a curative treatment raised by the work of Dr. Thompson and her colleagues also shows the feasibility of transfusion independence for beta0/betaE patients, who carry the most common beta thalassemia genotype, and a significant reduction in transfusions even for patients with the more severe beta0/beta0 genotype.
Beta thalassemia has greatest prevalence in North Africa, the Middle East, and Asia, where access to treatments is limited and patients’ prognoses are often grim. Gene therapy for beta thalassemia could thereby represent the first large-scale implementation of this intervention in developing countries.
Bringing HSC gene therapy to more patients will require not just the availability of autologous HSCs, but of high-quality vector and reliable, high-volume manufacturing of transduced cells.
Harnessing this still-evolving technology to bring a potentially curative treatment to patients in developing countries is an exciting, but challenging, frontier for physicians and researchers involved with gene therapy.
Alessandra Biffi, MD, is director of the gene therapy program at Dana Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, Boston. She serves on the board of directors of the American Society of Gene and Cell Therapy. These remarks were adapted from an accompanying editorial ( N Engl J Med. 2018;378[16]:1551-2 ).
Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.
Of 13 patients who did not have the most severe beta0/beta0 genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta0/beta0 genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.
At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.
“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.
Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.
Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.
There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.
In both studies, after mobilization, patients’ unmanipulated hematopoietic stem cells and progenitor cells were taken to a central processing facility, where CD34+ cells were enriched and then transduced with the lentiviral vector BB305, which encodes adult hemoglobin (HbA) with a T87Z amino acid substitution and thereby provides functioning Hb beta. Patients received the product via infusion after undergoing myeloablative conditioning with busulfan.
A total of 23 patients, 19 in the international study and 4 in the French study, went through mobilization and apheresis. One patient in the international study had apheresis failure, so a total of 22 patients received LentiGlobin, and all were followed for up to 2 years.
Patients were given the opportunity to participate in a follow-on open label study meant to continue for an additional 13 years after the initial 24-month period; 13 patients are currently enrolled in this long-term follow-up study.
When transfusion volume at baseline was assessed, patients in the international study were receiving a median annual red blood cell transfusion volume of 164 mL/kg per year, while the French study participants were receiving a median 182 mL/kg per year of red blood cell transfusion.
In both studies, blood HbAT87Q levels correlated with the vector copy numbers (R2, 0.75; P less than .001). Levels of HbAT87Q ranged from 3.4-10.0 g/dL.
“Other factors, such as age, genotype, and splenectomy status, did not appear to correlate with gene expression,” the researchers wrote.
An exploratory analysis looked at characteristics of patients who were able to stop transfusions after gene therapy. In this group, “the degree of hemolysis at first stabilized relative to pretransplantation levels and was fully corrected” in two patients by 36 months after treatment.
The researchers noted that the sponsor achieved “high-titer, large-scale, clinical-grade BB305 vector production and purification by ion-exchange chromatography” from a single site in the United States, which showed the feasibility of conducting this modality of gene therapy at scale.
The study was sponsored by bluebird bio, the National Institutes of Health, and by French national research organizations. Dr. Thompson reported research funding and fees from bluebird bio and other pharmaceutical companies.
SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93
Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.
Of 13 patients who did not have the most severe beta0/beta0 genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta0/beta0 genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.
At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.
“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.
Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.
Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.
There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.
In both studies, after mobilization, patients’ unmanipulated hematopoietic stem cells and progenitor cells were taken to a central processing facility, where CD34+ cells were enriched and then transduced with the lentiviral vector BB305, which encodes adult hemoglobin (HbA) with a T87Z amino acid substitution and thereby provides functioning Hb beta. Patients received the product via infusion after undergoing myeloablative conditioning with busulfan.
A total of 23 patients, 19 in the international study and 4 in the French study, went through mobilization and apheresis. One patient in the international study had apheresis failure, so a total of 22 patients received LentiGlobin, and all were followed for up to 2 years.
Patients were given the opportunity to participate in a follow-on open label study meant to continue for an additional 13 years after the initial 24-month period; 13 patients are currently enrolled in this long-term follow-up study.
When transfusion volume at baseline was assessed, patients in the international study were receiving a median annual red blood cell transfusion volume of 164 mL/kg per year, while the French study participants were receiving a median 182 mL/kg per year of red blood cell transfusion.
In both studies, blood HbAT87Q levels correlated with the vector copy numbers (R2, 0.75; P less than .001). Levels of HbAT87Q ranged from 3.4-10.0 g/dL.
“Other factors, such as age, genotype, and splenectomy status, did not appear to correlate with gene expression,” the researchers wrote.
An exploratory analysis looked at characteristics of patients who were able to stop transfusions after gene therapy. In this group, “the degree of hemolysis at first stabilized relative to pretransplantation levels and was fully corrected” in two patients by 36 months after treatment.
The researchers noted that the sponsor achieved “high-titer, large-scale, clinical-grade BB305 vector production and purification by ion-exchange chromatography” from a single site in the United States, which showed the feasibility of conducting this modality of gene therapy at scale.
The study was sponsored by bluebird bio, the National Institutes of Health, and by French national research organizations. Dr. Thompson reported research funding and fees from bluebird bio and other pharmaceutical companies.
SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Transfusion requirements were down 73% annually in patients with the most severe thalassemia.
Study details: Data from 22 transfusion-dependent patients with beta thalassemia in ongoing phase 1/2 study of gene therapy delivered via lentiviral vector.
Disclosures: The study was sponsored by bluebird bio, the National Institutes of Health, and by French national research organizations. Dr. Thompson reported research funding and fees from bluebird bio and from other pharmaceutical companies.
Source: Thompson A et al. N Engl J Med. 2018;378:1479-93.
Meta-analysis finds no link between stroke and sickle cell trait
Those findings contrast with an earlier longitudinal study that found a 1.4-fold risk of ischemic stroke in SCT carriers, the authors noted.
In their study, neither crude stroke incidence rates nor regression analysis indicated a link between SCT and stroke, said first author Hyacinth I. Hyacinth, MD, PhD, MPH, of the Aflac Cancer and Blood Disorder Center, Emory University, Atlanta, and his coauthors.
“The absence of an association between SCT and risk of ischemic stroke was consistent among the cohorts, and suggests that SCT is not an independent genetic risk factor for ischemic stroke among African Americans,” Dr. Hyacinth and his coauthors wrote.
The results may have implications for patient care. In particular, a more thorough evaluation of stroke in a patient with SCT may be warranted, instead of assuming that the SCT is an underlying cause of the stroke, they said.
The meta-analysis included a total of 19,464 subjects from four large, prospective, population-based studies with African American cohorts.
Results of the meta-analysis show that crude incidence of stroke was similar for individuals with SCT, at 2.9 per 1,000 person-years (95% confidence interval, 2.2-4.0), and for those with no SCT, at 3.2 per 1,000 person-years (95% CI, 2.7-3.8).
After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = 0.82), results further show.
It’s unclear why this study found no association between SCT and stroke when the earlier population-based study suggested a link between the two. Dr. Hyacinth and his coauthors suggested differences in study methods or proportion of individuals at risk for stroke may account for the divergent findings. They also controlled for left ventricular hypertrophy, while the previous study did not.
“However, in our analysis, adjusting for left ventricular hypertrophy did not change the direction of estimate effects,” they said in the report.
Further study is needed to determine whether or not SCT may be linked to a particular type of stroke. “We were unable to test the association of SCT with ischemic stroke subtypes,” the authors noted.
Dr. Hyacinth and his coauthors reported no conflicts of interest related to the study.
SOURCE: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi:10.1001/jamaneurol.2018.0571
Those findings contrast with an earlier longitudinal study that found a 1.4-fold risk of ischemic stroke in SCT carriers, the authors noted.
In their study, neither crude stroke incidence rates nor regression analysis indicated a link between SCT and stroke, said first author Hyacinth I. Hyacinth, MD, PhD, MPH, of the Aflac Cancer and Blood Disorder Center, Emory University, Atlanta, and his coauthors.
“The absence of an association between SCT and risk of ischemic stroke was consistent among the cohorts, and suggests that SCT is not an independent genetic risk factor for ischemic stroke among African Americans,” Dr. Hyacinth and his coauthors wrote.
The results may have implications for patient care. In particular, a more thorough evaluation of stroke in a patient with SCT may be warranted, instead of assuming that the SCT is an underlying cause of the stroke, they said.
The meta-analysis included a total of 19,464 subjects from four large, prospective, population-based studies with African American cohorts.
Results of the meta-analysis show that crude incidence of stroke was similar for individuals with SCT, at 2.9 per 1,000 person-years (95% confidence interval, 2.2-4.0), and for those with no SCT, at 3.2 per 1,000 person-years (95% CI, 2.7-3.8).
After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = 0.82), results further show.
It’s unclear why this study found no association between SCT and stroke when the earlier population-based study suggested a link between the two. Dr. Hyacinth and his coauthors suggested differences in study methods or proportion of individuals at risk for stroke may account for the divergent findings. They also controlled for left ventricular hypertrophy, while the previous study did not.
“However, in our analysis, adjusting for left ventricular hypertrophy did not change the direction of estimate effects,” they said in the report.
Further study is needed to determine whether or not SCT may be linked to a particular type of stroke. “We were unable to test the association of SCT with ischemic stroke subtypes,” the authors noted.
Dr. Hyacinth and his coauthors reported no conflicts of interest related to the study.
SOURCE: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi:10.1001/jamaneurol.2018.0571
Those findings contrast with an earlier longitudinal study that found a 1.4-fold risk of ischemic stroke in SCT carriers, the authors noted.
In their study, neither crude stroke incidence rates nor regression analysis indicated a link between SCT and stroke, said first author Hyacinth I. Hyacinth, MD, PhD, MPH, of the Aflac Cancer and Blood Disorder Center, Emory University, Atlanta, and his coauthors.
“The absence of an association between SCT and risk of ischemic stroke was consistent among the cohorts, and suggests that SCT is not an independent genetic risk factor for ischemic stroke among African Americans,” Dr. Hyacinth and his coauthors wrote.
The results may have implications for patient care. In particular, a more thorough evaluation of stroke in a patient with SCT may be warranted, instead of assuming that the SCT is an underlying cause of the stroke, they said.
The meta-analysis included a total of 19,464 subjects from four large, prospective, population-based studies with African American cohorts.
Results of the meta-analysis show that crude incidence of stroke was similar for individuals with SCT, at 2.9 per 1,000 person-years (95% confidence interval, 2.2-4.0), and for those with no SCT, at 3.2 per 1,000 person-years (95% CI, 2.7-3.8).
After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = 0.82), results further show.
It’s unclear why this study found no association between SCT and stroke when the earlier population-based study suggested a link between the two. Dr. Hyacinth and his coauthors suggested differences in study methods or proportion of individuals at risk for stroke may account for the divergent findings. They also controlled for left ventricular hypertrophy, while the previous study did not.
“However, in our analysis, adjusting for left ventricular hypertrophy did not change the direction of estimate effects,” they said in the report.
Further study is needed to determine whether or not SCT may be linked to a particular type of stroke. “We were unable to test the association of SCT with ischemic stroke subtypes,” the authors noted.
Dr. Hyacinth and his coauthors reported no conflicts of interest related to the study.
SOURCE: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi:10.1001/jamaneurol.2018.0571
FROM JAMA NEUROLOGY
Key clinical point: In contrast to results of a previous study, a meta-analysis has found no evidence linking sickle cell trait (SCT) and risk of incident ischemic stroke in African Americans.
Major finding: Crude stroke incidence was not different for SCT versus no SCT. After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = .82).
Study details: A meta-analysis of the association between SCT and risk of incident ischemic stroke in four large prospective, population-based studies with African American cohorts (19,464 total subjects).
Disclosures: Authors reported no conflicts of interest related to the study.
Source: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0571.
Art education benefits blood cancer patients
New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.
The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.
After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.
Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.
The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.
The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).
Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.
Intervention
The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.
Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.
Results
The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.
After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).
Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).
In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.
Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.
All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.
The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.
New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.
The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.
After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.
Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.
The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.
The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).
Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.
Intervention
The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.
Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.
Results
The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.
After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).
Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).
In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.
Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.
All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.
The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.
New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.
The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.
After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.
Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.
The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.
The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).
Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.
Intervention
The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.
Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.
Results
The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.
After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).
Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).
In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.
Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.
All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.
The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.