HT Staff

Mother and infant
Photo credit: Vera Kratochvil

A single-center retrospective study of 39 pregnant women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy indicates that delaying treatment until the second trimester is “likely safe and results in acceptable” outcomes for both mother and child.

Investigators also found that deferring therapy until after delivery did not adversely affect maternal outcomes.

In order to clarify the sometimes conflicting reports regarding management of lymphoma during pregnancy, investigators at MD Anderson Cancer Center in Houston, Texas, undertook the study to determine whether administering standard chemotherapy during the second and third trimesters has acceptable maternal and fetal outcomes.

Michelle A. Fanale, MD, and colleagues published their findings in JAMA Oncology.

Patient characteristics

Investigators identified 31 women with HL and 8 with NHL who were diagnosed between 1991 and 2014 and had sufficient pregnancy and follow-up data.
 
The women were a median age of 28 years (range 19-38). The patients with NHL were significantly older, P=0.004.

Approximately 20% of patients had B symptoms. Most were stage II disease (72%), and 80% were ECOG performance status 0 or 1.

About two thirds of patients had hemoglobin levels less than 12 g/dL.

Most patients did not have extranodal nonbone-marrow disease (82%), although there was a significant difference between those with HL (90%) and NHL (50%), P=0.03.

One third of patients had bulky disease, and 88% were in their second or third trimesters at diagnosis.

Three women electively terminated their pregnancies at diagnosis. Of the 36 remaining patients, 24 (61%) began antenatal therapy and 12 (31%) postponed therapy until after delivery.

Four patients received radiation therapy above the diaphragm at a median dose of 40.4 Gy.

Obstetric outcomes

Antenatal therapy was not associated with increased incidence of preterm delivery. Of the 24 women who received treatment during pregnancy, 7 (29%) gave birth prematurely compared with 5 of the 12 women (42%) who postponed treatment until after delivery, P=0.73.

The investigators noted that the miscarriage rate was approximately 10%, which was higher than previous studies.

Four patients had miscarriages, 2 during the first trimester and 2 during the second. Both patients who had miscarriages in the first trimester had received lymphoma treatment during that time.

And one of the patients who had antenatal therapy during the second trimester and had a miscarriage was critically ill, which the investigators believed was a contributing factor.

The second woman who miscarried after therapy in the second trimester had conceived twins through in vitro fertilization and miscarried at 23 weeks after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) therapy had been initiated at gestational week 15.

Investigators had fetal outcomes available for 31 of 32 patients who did not terminate or have a miscarriage. And these 31 infants had no anomalies at birth.

The investigators said that although the follow-up time is relatively short, they observed no malformations in the newborns.

Treatment responses and survival

The overall response rate (OR) was 91.7% and the complete response (CR) rate was 75.0% for the 24 patients who started treatment during pregnancy.

And for those 12 women who deferred therapy until delivery, both ORR and CR rates were 91.7%.

The 5-year progression-free survival (PFS) and OS were 74.7% and 82.4%, respectively, for all women. The median follow-up was 67.9 months (range 8.8 to 277.5).

For the 31 women with HL, the 5-year PFS and OS were 69.9% and 80%, respectively.

And for the 8 women with NHL, the 5-year PFS and OS were 85.7% and 83.3%, respectively.

Investigators found no difference in PFS or OS (P=0.84) based on undergoing antenatal lymphoma treatment among the 36 women who did not terminate their pregnancies at diagnosis.

The investigators conducted a univariate analysis and found that for the 36 women who did not electively terminate their pregnancies, the following were associated with increased risk of disease progression:

•    Bulky disease—hazard ratio [HR] 3.6, P = 0.06
•    Extranodal nonbone marrow involvement—HR 4.2, P = 0.04
•    Poor ECOG performance status—HR 3.9, P = 0.005

Poor performance status was also associated with OS, HR 8.88, P = 0.004.

Multivariate analysis revealed significant associations in terms of OS and PFS for extranodal nonbone marrow involvement and performance status:

•    Nonbone marrow involvement—OS HR, 73.5, P = 0.02; PFS HR 8.26, P = 0.01
•    Performance status—OS HR, 26.7, P = 0.003; PFS HR, 4.89, P = 0.002

The investigators concluded that because they found no differences in PFS or OS according to whether patients received antenatal therapy, they believe that disease factors, rather than treatment-related factors, influence worse maternal outcomes.

They recommended delaying therapy until the second trimester if that can be accomplished without harm to the patient.

Mother and infant
Photo credit: Vera Kratochvil

A single-center retrospective study of 39 pregnant women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy indicates that delaying treatment until the second trimester is “likely safe and results in acceptable” outcomes for both mother and child.

Investigators also found that deferring therapy until after delivery did not adversely affect maternal outcomes.

In order to clarify the sometimes conflicting reports regarding management of lymphoma during pregnancy, investigators at MD Anderson Cancer Center in Houston, Texas, undertook the study to determine whether administering standard chemotherapy during the second and third trimesters has acceptable maternal and fetal outcomes.

Michelle A. Fanale, MD, and colleagues published their findings in JAMA Oncology.

Patient characteristics

Investigators identified 31 women with HL and 8 with NHL who were diagnosed between 1991 and 2014 and had sufficient pregnancy and follow-up data.
 
The women were a median age of 28 years (range 19-38). The patients with NHL were significantly older, P=0.004.

Approximately 20% of patients had B symptoms. Most were stage II disease (72%), and 80% were ECOG performance status 0 or 1.

About two thirds of patients had hemoglobin levels less than 12 g/dL.

Most patients did not have extranodal nonbone-marrow disease (82%), although there was a significant difference between those with HL (90%) and NHL (50%), P=0.03.

One third of patients had bulky disease, and 88% were in their second or third trimesters at diagnosis.

Three women electively terminated their pregnancies at diagnosis. Of the 36 remaining patients, 24 (61%) began antenatal therapy and 12 (31%) postponed therapy until after delivery.

Four patients received radiation therapy above the diaphragm at a median dose of 40.4 Gy.

Obstetric outcomes

Antenatal therapy was not associated with increased incidence of preterm delivery. Of the 24 women who received treatment during pregnancy, 7 (29%) gave birth prematurely compared with 5 of the 12 women (42%) who postponed treatment until after delivery, P=0.73.

The investigators noted that the miscarriage rate was approximately 10%, which was higher than previous studies.

Four patients had miscarriages, 2 during the first trimester and 2 during the second. Both patients who had miscarriages in the first trimester had received lymphoma treatment during that time.

And one of the patients who had antenatal therapy during the second trimester and had a miscarriage was critically ill, which the investigators believed was a contributing factor.

The second woman who miscarried after therapy in the second trimester had conceived twins through in vitro fertilization and miscarried at 23 weeks after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) therapy had been initiated at gestational week 15.

Investigators had fetal outcomes available for 31 of 32 patients who did not terminate or have a miscarriage. And these 31 infants had no anomalies at birth.

The investigators said that although the follow-up time is relatively short, they observed no malformations in the newborns.

Treatment responses and survival

The overall response rate (OR) was 91.7% and the complete response (CR) rate was 75.0% for the 24 patients who started treatment during pregnancy.

And for those 12 women who deferred therapy until delivery, both ORR and CR rates were 91.7%.

The 5-year progression-free survival (PFS) and OS were 74.7% and 82.4%, respectively, for all women. The median follow-up was 67.9 months (range 8.8 to 277.5).

For the 31 women with HL, the 5-year PFS and OS were 69.9% and 80%, respectively.

And for the 8 women with NHL, the 5-year PFS and OS were 85.7% and 83.3%, respectively.

Investigators found no difference in PFS or OS (P=0.84) based on undergoing antenatal lymphoma treatment among the 36 women who did not terminate their pregnancies at diagnosis.

The investigators conducted a univariate analysis and found that for the 36 women who did not electively terminate their pregnancies, the following were associated with increased risk of disease progression:

•    Bulky disease—hazard ratio [HR] 3.6, P = 0.06
•    Extranodal nonbone marrow involvement—HR 4.2, P = 0.04
•    Poor ECOG performance status—HR 3.9, P = 0.005

Poor performance status was also associated with OS, HR 8.88, P = 0.004.

Multivariate analysis revealed significant associations in terms of OS and PFS for extranodal nonbone marrow involvement and performance status:

•    Nonbone marrow involvement—OS HR, 73.5, P = 0.02; PFS HR 8.26, P = 0.01
•    Performance status—OS HR, 26.7, P = 0.003; PFS HR, 4.89, P = 0.002

The investigators concluded that because they found no differences in PFS or OS according to whether patients received antenatal therapy, they believe that disease factors, rather than treatment-related factors, influence worse maternal outcomes.

They recommended delaying therapy until the second trimester if that can be accomplished without harm to the patient.

Mother and infant
Photo credit: Vera Kratochvil

A single-center retrospective study of 39 pregnant women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy indicates that delaying treatment until the second trimester is “likely safe and results in acceptable” outcomes for both mother and child.

Investigators also found that deferring therapy until after delivery did not adversely affect maternal outcomes.

In order to clarify the sometimes conflicting reports regarding management of lymphoma during pregnancy, investigators at MD Anderson Cancer Center in Houston, Texas, undertook the study to determine whether administering standard chemotherapy during the second and third trimesters has acceptable maternal and fetal outcomes.

Michelle A. Fanale, MD, and colleagues published their findings in JAMA Oncology.

Patient characteristics

Investigators identified 31 women with HL and 8 with NHL who were diagnosed between 1991 and 2014 and had sufficient pregnancy and follow-up data.
 
The women were a median age of 28 years (range 19-38). The patients with NHL were significantly older, P=0.004.

Approximately 20% of patients had B symptoms. Most were stage II disease (72%), and 80% were ECOG performance status 0 or 1.

About two thirds of patients had hemoglobin levels less than 12 g/dL.

Most patients did not have extranodal nonbone-marrow disease (82%), although there was a significant difference between those with HL (90%) and NHL (50%), P=0.03.

One third of patients had bulky disease, and 88% were in their second or third trimesters at diagnosis.

Three women electively terminated their pregnancies at diagnosis. Of the 36 remaining patients, 24 (61%) began antenatal therapy and 12 (31%) postponed therapy until after delivery.

Four patients received radiation therapy above the diaphragm at a median dose of 40.4 Gy.

Obstetric outcomes

Antenatal therapy was not associated with increased incidence of preterm delivery. Of the 24 women who received treatment during pregnancy, 7 (29%) gave birth prematurely compared with 5 of the 12 women (42%) who postponed treatment until after delivery, P=0.73.

The investigators noted that the miscarriage rate was approximately 10%, which was higher than previous studies.

Four patients had miscarriages, 2 during the first trimester and 2 during the second. Both patients who had miscarriages in the first trimester had received lymphoma treatment during that time.

And one of the patients who had antenatal therapy during the second trimester and had a miscarriage was critically ill, which the investigators believed was a contributing factor.

The second woman who miscarried after therapy in the second trimester had conceived twins through in vitro fertilization and miscarried at 23 weeks after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) therapy had been initiated at gestational week 15.

Investigators had fetal outcomes available for 31 of 32 patients who did not terminate or have a miscarriage. And these 31 infants had no anomalies at birth.

The investigators said that although the follow-up time is relatively short, they observed no malformations in the newborns.

Treatment responses and survival

The overall response rate (OR) was 91.7% and the complete response (CR) rate was 75.0% for the 24 patients who started treatment during pregnancy.

And for those 12 women who deferred therapy until delivery, both ORR and CR rates were 91.7%.

The 5-year progression-free survival (PFS) and OS were 74.7% and 82.4%, respectively, for all women. The median follow-up was 67.9 months (range 8.8 to 277.5).

For the 31 women with HL, the 5-year PFS and OS were 69.9% and 80%, respectively.

And for the 8 women with NHL, the 5-year PFS and OS were 85.7% and 83.3%, respectively.

Investigators found no difference in PFS or OS (P=0.84) based on undergoing antenatal lymphoma treatment among the 36 women who did not terminate their pregnancies at diagnosis.

The investigators conducted a univariate analysis and found that for the 36 women who did not electively terminate their pregnancies, the following were associated with increased risk of disease progression:

•    Bulky disease—hazard ratio [HR] 3.6, P = 0.06
•    Extranodal nonbone marrow involvement—HR 4.2, P = 0.04
•    Poor ECOG performance status—HR 3.9, P = 0.005

Poor performance status was also associated with OS, HR 8.88, P = 0.004.

Multivariate analysis revealed significant associations in terms of OS and PFS for extranodal nonbone marrow involvement and performance status:

•    Nonbone marrow involvement—OS HR, 73.5, P = 0.02; PFS HR 8.26, P = 0.01
•    Performance status—OS HR, 26.7, P = 0.003; PFS HR, 4.89, P = 0.002

The investigators concluded that because they found no differences in PFS or OS according to whether patients received antenatal therapy, they believe that disease factors, rather than treatment-related factors, influence worse maternal outcomes.

They recommended delaying therapy until the second trimester if that can be accomplished without harm to the patient.

Doctor and patient in hospital
Photo courtesy of the CDC

A new study sheds light on whether an increased risk of death in the 30 days to 2 years after contracting sepsis is caused by sepsis itself, or because of pre-existing health conditions the patients had before acquiring the complication.

Using detailed survey data and medical records of more than 30,000 older Americans, the researchers conducted a propensity matched cohort study to investigate the phenomenon of late death after sepsis.

Late death refers to deaths that take place months to years after the acute infection has resolved.

"We know sicker patients are more likely to develop sepsis," lead author Hallie Prescott, MD, of the University of Michigan in Ann Arbor, said. "And that made us wonder: Perhaps those previous health conditions are driving the risk of late death after sepsis?"

So the investigators compared 960 patients aged 65 or older who were admitted to the hospital with sepsis to 3 control groups: 777 adults not currently hospitalized, 788 patients hospitalized with non-sepsis infections, and 504 patients admitted with acute sterile inflammatory conditions.

All patients had participated in the US Health and Retirement Study, a longitudinal survey of 37,000 adults aged over 50 in 23,000 households. The survey is considered broadly representative of the older US population.

The current study included Medicare beneficiaries who had participated in at least one survey between 1998 and 2008.

The main outcome measure was late mortality 31 days to 2 years after sepsis and odds of death at various intervals.

Results

In the sepsis cohort, the mean age was 79, 54% were women, 81% were white, and 12% were nursing home residents.

There were no significant differences among the cohorts in terms of demographics, socioeconomic characteristics, baseline health status, or recent healthcare use.

The sepsis cohort had a 25.4% mortality rate at 30 days, 35.3% at 90 days, 41.3% at 180 days, 48.5% at 1 year, and 56.5% at 2 years.

Over 40% of sepsis patients who survived 30 days after their hospitalization died in the next 2 years. If sepsis patients survived to a year, the adjusted 2-year mortality was 16.0% versus 10.7% for controls not in the hospital.

When investigators compared these mortality rates to matched patients who were not hospitalized, they found that those with sepsis experienced a 22.1% absolute increase in late mortality. This translated into a 2.2-fold relative increase in late mortality.

And when they compared the sepsis patients to patients hospitalized for non-sepsis infections, the investigators determined that sepsis patients experienced a 10.4% absolute increase in late mortality. This translated into a 1.3-fold relative increase in late mortality.

Finally, they compared the sepsis patients to those patients hospitalized for sterile inflammatory conditions and found that the sepsis patients who survived to 31 days experienced a 16.2% absolute increase in late mortality. This translated into 1.6-fold relative increase.

The investigators said this high rate of late mortality could not be explained by the patients’ age, socio-demographics, or their pre-sepsis health status.

"Rather, we found that, compared to the group of adults not in the hospital,” Dr Prescott said, “1 in 5 patients who survived sepsis had a late death that was not explained by their baseline characteristics.”

The investigators said this suggests that late mortality after sepsis could be more amendable to intervention than previously thought.

The investigators published their findings in BMJ.

Doctor and patient in hospital
Photo courtesy of the CDC

A new study sheds light on whether an increased risk of death in the 30 days to 2 years after contracting sepsis is caused by sepsis itself, or because of pre-existing health conditions the patients had before acquiring the complication.

Using detailed survey data and medical records of more than 30,000 older Americans, the researchers conducted a propensity matched cohort study to investigate the phenomenon of late death after sepsis.

Late death refers to deaths that take place months to years after the acute infection has resolved.

"We know sicker patients are more likely to develop sepsis," lead author Hallie Prescott, MD, of the University of Michigan in Ann Arbor, said. "And that made us wonder: Perhaps those previous health conditions are driving the risk of late death after sepsis?"

So the investigators compared 960 patients aged 65 or older who were admitted to the hospital with sepsis to 3 control groups: 777 adults not currently hospitalized, 788 patients hospitalized with non-sepsis infections, and 504 patients admitted with acute sterile inflammatory conditions.

All patients had participated in the US Health and Retirement Study, a longitudinal survey of 37,000 adults aged over 50 in 23,000 households. The survey is considered broadly representative of the older US population.

The current study included Medicare beneficiaries who had participated in at least one survey between 1998 and 2008.

The main outcome measure was late mortality 31 days to 2 years after sepsis and odds of death at various intervals.

Results

In the sepsis cohort, the mean age was 79, 54% were women, 81% were white, and 12% were nursing home residents.

There were no significant differences among the cohorts in terms of demographics, socioeconomic characteristics, baseline health status, or recent healthcare use.

The sepsis cohort had a 25.4% mortality rate at 30 days, 35.3% at 90 days, 41.3% at 180 days, 48.5% at 1 year, and 56.5% at 2 years.

Over 40% of sepsis patients who survived 30 days after their hospitalization died in the next 2 years. If sepsis patients survived to a year, the adjusted 2-year mortality was 16.0% versus 10.7% for controls not in the hospital.

When investigators compared these mortality rates to matched patients who were not hospitalized, they found that those with sepsis experienced a 22.1% absolute increase in late mortality. This translated into a 2.2-fold relative increase in late mortality.

And when they compared the sepsis patients to patients hospitalized for non-sepsis infections, the investigators determined that sepsis patients experienced a 10.4% absolute increase in late mortality. This translated into a 1.3-fold relative increase in late mortality.

Finally, they compared the sepsis patients to those patients hospitalized for sterile inflammatory conditions and found that the sepsis patients who survived to 31 days experienced a 16.2% absolute increase in late mortality. This translated into 1.6-fold relative increase.

The investigators said this high rate of late mortality could not be explained by the patients’ age, socio-demographics, or their pre-sepsis health status.

"Rather, we found that, compared to the group of adults not in the hospital,” Dr Prescott said, “1 in 5 patients who survived sepsis had a late death that was not explained by their baseline characteristics.”

The investigators said this suggests that late mortality after sepsis could be more amendable to intervention than previously thought.

The investigators published their findings in BMJ.

Doctor and patient in hospital
Photo courtesy of the CDC

A new study sheds light on whether an increased risk of death in the 30 days to 2 years after contracting sepsis is caused by sepsis itself, or because of pre-existing health conditions the patients had before acquiring the complication.

Using detailed survey data and medical records of more than 30,000 older Americans, the researchers conducted a propensity matched cohort study to investigate the phenomenon of late death after sepsis.

Late death refers to deaths that take place months to years after the acute infection has resolved.

"We know sicker patients are more likely to develop sepsis," lead author Hallie Prescott, MD, of the University of Michigan in Ann Arbor, said. "And that made us wonder: Perhaps those previous health conditions are driving the risk of late death after sepsis?"

So the investigators compared 960 patients aged 65 or older who were admitted to the hospital with sepsis to 3 control groups: 777 adults not currently hospitalized, 788 patients hospitalized with non-sepsis infections, and 504 patients admitted with acute sterile inflammatory conditions.

All patients had participated in the US Health and Retirement Study, a longitudinal survey of 37,000 adults aged over 50 in 23,000 households. The survey is considered broadly representative of the older US population.

The current study included Medicare beneficiaries who had participated in at least one survey between 1998 and 2008.

The main outcome measure was late mortality 31 days to 2 years after sepsis and odds of death at various intervals.

Results

In the sepsis cohort, the mean age was 79, 54% were women, 81% were white, and 12% were nursing home residents.

There were no significant differences among the cohorts in terms of demographics, socioeconomic characteristics, baseline health status, or recent healthcare use.

The sepsis cohort had a 25.4% mortality rate at 30 days, 35.3% at 90 days, 41.3% at 180 days, 48.5% at 1 year, and 56.5% at 2 years.

Over 40% of sepsis patients who survived 30 days after their hospitalization died in the next 2 years. If sepsis patients survived to a year, the adjusted 2-year mortality was 16.0% versus 10.7% for controls not in the hospital.

When investigators compared these mortality rates to matched patients who were not hospitalized, they found that those with sepsis experienced a 22.1% absolute increase in late mortality. This translated into a 2.2-fold relative increase in late mortality.

And when they compared the sepsis patients to patients hospitalized for non-sepsis infections, the investigators determined that sepsis patients experienced a 10.4% absolute increase in late mortality. This translated into a 1.3-fold relative increase in late mortality.

Finally, they compared the sepsis patients to those patients hospitalized for sterile inflammatory conditions and found that the sepsis patients who survived to 31 days experienced a 16.2% absolute increase in late mortality. This translated into 1.6-fold relative increase.

The investigators said this high rate of late mortality could not be explained by the patients’ age, socio-demographics, or their pre-sepsis health status.

"Rather, we found that, compared to the group of adults not in the hospital,” Dr Prescott said, “1 in 5 patients who survived sepsis had a late death that was not explained by their baseline characteristics.”

The investigators said this suggests that late mortality after sepsis could be more amendable to intervention than previously thought.

The investigators published their findings in BMJ.

Poster session at ASCO 2016

© ASCO/Zach Boyden-Holmes

CHICAGO—Hispanic white and non-Hispanic black adolescents and young adults (AYA) are more likely to die of their disease than the same-aged white patients, according to a study presented at the 2016 ASCO Annual Meeting.

If the chance of a young-adult white patient dying within 2 years of receiving a liver cancer diagnosis is a baseline of 1, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient's chance of dying is 1.76.

And this holds true across cancer types, including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.

"What this means is that black and Hispanic young adult patients are almost 75% more likely to die after being diagnosed with liver cancer than are white young adult patients," said co-investigator Meryl Colton, a medical student at the University of Colorado.

Using data from the Surveillance, Epidemiologic and End Results (SEER) database, Colton and Adam L. Green, MD, of Children’s Hospital Colorado in Aurora, compared adolescents and young adults between the ages of 15 and 29 to evaluate racial/ethnic disparities in this age population, which is at particular risk for disparities in socioeconomic status and delayed diagnosis.

Even after controlling for insurance status and stage at diagnosis, the researchers determined that there were disparities in death rates for Hispanic whites, non-Hispanic blacks, and Hispanic blacks.

This implies that there is an influence of race/ethnicity independent of financial resources.

For leukemia, the hazard ratio was 1.15 for Hispanic whites and 1.05 for non-Hispanic blacks compared with non-Hispanic whites.

And for lymphoma, the hazard ratio was 1.28 for Hispanic whites and 1.07 for non-Hispanic blacks compared with the control group.

Colton points to 3 possible reasons for the disparity—residual socioeconomic factors that could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of the diseases to make cancers more dangerous in certain populations, or the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.

The researchers presented these findings as abstract 6557. They recommend further exploration to determine the mechanisms of these disparities.

Poster session at ASCO 2016

© ASCO/Zach Boyden-Holmes

CHICAGO—Hispanic white and non-Hispanic black adolescents and young adults (AYA) are more likely to die of their disease than the same-aged white patients, according to a study presented at the 2016 ASCO Annual Meeting.

If the chance of a young-adult white patient dying within 2 years of receiving a liver cancer diagnosis is a baseline of 1, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient's chance of dying is 1.76.

And this holds true across cancer types, including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.

"What this means is that black and Hispanic young adult patients are almost 75% more likely to die after being diagnosed with liver cancer than are white young adult patients," said co-investigator Meryl Colton, a medical student at the University of Colorado.

Using data from the Surveillance, Epidemiologic and End Results (SEER) database, Colton and Adam L. Green, MD, of Children’s Hospital Colorado in Aurora, compared adolescents and young adults between the ages of 15 and 29 to evaluate racial/ethnic disparities in this age population, which is at particular risk for disparities in socioeconomic status and delayed diagnosis.

Even after controlling for insurance status and stage at diagnosis, the researchers determined that there were disparities in death rates for Hispanic whites, non-Hispanic blacks, and Hispanic blacks.

This implies that there is an influence of race/ethnicity independent of financial resources.

For leukemia, the hazard ratio was 1.15 for Hispanic whites and 1.05 for non-Hispanic blacks compared with non-Hispanic whites.

And for lymphoma, the hazard ratio was 1.28 for Hispanic whites and 1.07 for non-Hispanic blacks compared with the control group.

Colton points to 3 possible reasons for the disparity—residual socioeconomic factors that could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of the diseases to make cancers more dangerous in certain populations, or the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.

The researchers presented these findings as abstract 6557. They recommend further exploration to determine the mechanisms of these disparities.

Poster session at ASCO 2016

© ASCO/Zach Boyden-Holmes

CHICAGO—Hispanic white and non-Hispanic black adolescents and young adults (AYA) are more likely to die of their disease than the same-aged white patients, according to a study presented at the 2016 ASCO Annual Meeting.

If the chance of a young-adult white patient dying within 2 years of receiving a liver cancer diagnosis is a baseline of 1, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient's chance of dying is 1.76.

And this holds true across cancer types, including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.

"What this means is that black and Hispanic young adult patients are almost 75% more likely to die after being diagnosed with liver cancer than are white young adult patients," said co-investigator Meryl Colton, a medical student at the University of Colorado.

Using data from the Surveillance, Epidemiologic and End Results (SEER) database, Colton and Adam L. Green, MD, of Children’s Hospital Colorado in Aurora, compared adolescents and young adults between the ages of 15 and 29 to evaluate racial/ethnic disparities in this age population, which is at particular risk for disparities in socioeconomic status and delayed diagnosis.

Even after controlling for insurance status and stage at diagnosis, the researchers determined that there were disparities in death rates for Hispanic whites, non-Hispanic blacks, and Hispanic blacks.

This implies that there is an influence of race/ethnicity independent of financial resources.

For leukemia, the hazard ratio was 1.15 for Hispanic whites and 1.05 for non-Hispanic blacks compared with non-Hispanic whites.

And for lymphoma, the hazard ratio was 1.28 for Hispanic whites and 1.07 for non-Hispanic blacks compared with the control group.

Colton points to 3 possible reasons for the disparity—residual socioeconomic factors that could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of the diseases to make cancers more dangerous in certain populations, or the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.

The researchers presented these findings as abstract 6557. They recommend further exploration to determine the mechanisms of these disparities.

Ibrutinib (Imbruvica)
Photo from Janssen Biotech

The European Commission (EC) has broadened the indication for ibrutinib (Imbruvica) to include newly diagnosed patients with chronic lymphocytic leukemia (CLL).

The drug had already been approved in the European Union to treat adults with CLL who have received at least one prior therapy and adults with previously untreated CLL who have 17p deletion or TP53 mutation and are unsuitable for chemo-immunotherapy. 

Ibrutinib is now approved for all patients with CLL.

The EC is following the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which had previously sent its endorsement to the EC.

This approval also follows the decision by the US Food and Drug Administration in March to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Ibrutinib is also approved to treat adults with relapsed or refractory mantle cell lymphoma, adults with Waldenström’s macroglobulinemia who have received at least one prior therapy, and previously untreated adults with Waldenström’s macroglobulinemia who are unsuitable for chemo-immunotherapy.

RESONATE-2 trial

The expanded ibrutinib indication is based on data from the phase 3, randomized, open-label RESONATE-2 trial, published in NEJM in 2015.

Results from the RESONATE-2 study showed that ibrutinib significantly prolonged overall survival (OS) (HR=0.16, 95 percent CI 0.05 to 0.56; P=0.001).

Ninety-eight percent of patients were still alive after 2 years, compared to 85% percent for patients randomized to the chlorambucil arm. 

Median progression-free survival (PFS) was not reached for patients receiving ibrutinib versus 18.9 months for those in the chlorambucil arm. This represented a statistically significant 84% reduction in the risk of death or progression in the ibrutinib arm (HR=0.16, 95 percent CI 0.09 to 0.28; P<0.001). 

“Ibrutinib has shown remarkable improvements in overall survival, progression-free survival, and response rates compared with chlorambucil,” said Paolo Ghia, MD, PhD, one of the RESONATE-2 investigators.

The overall safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies. 

The most common adverse events for ibrutinib of any grade occurring in 20% or more of the patients were diarrhea (42%), fatigue (30%), cough (22%), and nausea (22%).

“The RESONATE-2 data indicate that ibrutinib can provide a much-needed first line treatment alternative for many patients,” Dr Ghia affirmed.

Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in all approved countries except the US. In the US, Janssen Biotech, Inc. and Pharmacyclics co-market it.

Ibrutinib (Imbruvica)
Photo from Janssen Biotech

The European Commission (EC) has broadened the indication for ibrutinib (Imbruvica) to include newly diagnosed patients with chronic lymphocytic leukemia (CLL).

The drug had already been approved in the European Union to treat adults with CLL who have received at least one prior therapy and adults with previously untreated CLL who have 17p deletion or TP53 mutation and are unsuitable for chemo-immunotherapy. 

Ibrutinib is now approved for all patients with CLL.

The EC is following the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which had previously sent its endorsement to the EC.

This approval also follows the decision by the US Food and Drug Administration in March to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Ibrutinib is also approved to treat adults with relapsed or refractory mantle cell lymphoma, adults with Waldenström’s macroglobulinemia who have received at least one prior therapy, and previously untreated adults with Waldenström’s macroglobulinemia who are unsuitable for chemo-immunotherapy.

RESONATE-2 trial

The expanded ibrutinib indication is based on data from the phase 3, randomized, open-label RESONATE-2 trial, published in NEJM in 2015.

Results from the RESONATE-2 study showed that ibrutinib significantly prolonged overall survival (OS) (HR=0.16, 95 percent CI 0.05 to 0.56; P=0.001).

Ninety-eight percent of patients were still alive after 2 years, compared to 85% percent for patients randomized to the chlorambucil arm. 

Median progression-free survival (PFS) was not reached for patients receiving ibrutinib versus 18.9 months for those in the chlorambucil arm. This represented a statistically significant 84% reduction in the risk of death or progression in the ibrutinib arm (HR=0.16, 95 percent CI 0.09 to 0.28; P<0.001). 

“Ibrutinib has shown remarkable improvements in overall survival, progression-free survival, and response rates compared with chlorambucil,” said Paolo Ghia, MD, PhD, one of the RESONATE-2 investigators.

The overall safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies. 

The most common adverse events for ibrutinib of any grade occurring in 20% or more of the patients were diarrhea (42%), fatigue (30%), cough (22%), and nausea (22%).

“The RESONATE-2 data indicate that ibrutinib can provide a much-needed first line treatment alternative for many patients,” Dr Ghia affirmed.

Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in all approved countries except the US. In the US, Janssen Biotech, Inc. and Pharmacyclics co-market it.

Ibrutinib (Imbruvica)
Photo from Janssen Biotech

The European Commission (EC) has broadened the indication for ibrutinib (Imbruvica) to include newly diagnosed patients with chronic lymphocytic leukemia (CLL).

The drug had already been approved in the European Union to treat adults with CLL who have received at least one prior therapy and adults with previously untreated CLL who have 17p deletion or TP53 mutation and are unsuitable for chemo-immunotherapy. 

Ibrutinib is now approved for all patients with CLL.

The EC is following the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which had previously sent its endorsement to the EC.

This approval also follows the decision by the US Food and Drug Administration in March to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Ibrutinib is also approved to treat adults with relapsed or refractory mantle cell lymphoma, adults with Waldenström’s macroglobulinemia who have received at least one prior therapy, and previously untreated adults with Waldenström’s macroglobulinemia who are unsuitable for chemo-immunotherapy.

RESONATE-2 trial

The expanded ibrutinib indication is based on data from the phase 3, randomized, open-label RESONATE-2 trial, published in NEJM in 2015.

Results from the RESONATE-2 study showed that ibrutinib significantly prolonged overall survival (OS) (HR=0.16, 95 percent CI 0.05 to 0.56; P=0.001).

Ninety-eight percent of patients were still alive after 2 years, compared to 85% percent for patients randomized to the chlorambucil arm. 

Median progression-free survival (PFS) was not reached for patients receiving ibrutinib versus 18.9 months for those in the chlorambucil arm. This represented a statistically significant 84% reduction in the risk of death or progression in the ibrutinib arm (HR=0.16, 95 percent CI 0.09 to 0.28; P<0.001). 

“Ibrutinib has shown remarkable improvements in overall survival, progression-free survival, and response rates compared with chlorambucil,” said Paolo Ghia, MD, PhD, one of the RESONATE-2 investigators.

The overall safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies. 

The most common adverse events for ibrutinib of any grade occurring in 20% or more of the patients were diarrhea (42%), fatigue (30%), cough (22%), and nausea (22%).

“The RESONATE-2 data indicate that ibrutinib can provide a much-needed first line treatment alternative for many patients,” Dr Ghia affirmed.

Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in all approved countries except the US. In the US, Janssen Biotech, Inc. and Pharmacyclics co-market it.

Plasmodium parasite
invading an RBC
Credit: St Jude Children's
Research Hospital

Two new anti-malaria drug candidates with different mechanisms of action—a pyrazoleamide and a spiroindolone—promote an influx of sodium ions into Plasmodium parasites that have invaded red blood cells and multiply there.

Within minutes, the increase in sodium kills the parasites, investigators believe, by changing its outer membrane and promoting division before its genome has been replicated.

Akhil Vaidya, PhD, of Drexel University College of Medicine in Philadelphia, and members of the research team published details of their findings in PLOS Pathogens.

The Plasmodium plasma membrane contains very low levels of cholesterol, which is a major lipid component of most other cell membranes. 

Saponin, a detergent that can dissolve cholesterol-containing membranes, dissolves red blood cells infected by Plasmodium and releases intact parasites into the bloodstream. The detergent is unable to destroy the parasites because their membranes have low cholesterol content.

However, when researchers exposed the parasite cell membranes to the 2 drugs, they became permeable by saponin. The researchers deemed this to be a function of the increased amount of cholesterol incorporated into the parasite membrane.

“We believe that the cholesterol makes the parasite rigid, and then the parasite can no longer pass through very small spaces in the bloodstream,” Dr Vaidya said. The parasite cannot continue its lifecycle if it cannot enter red blood cells.

Researchers also discovered that when drug exposure is short, the changes in membrane composition are reversible. The parasites regain their resistance to saponin most likely because the additional membrane cholesterol washes off.

After 2 hours of treatment with either drug, many of the parasites had fragmented nuclei and interior membranes. Researchers did not observe any sign of multiplication of the parasite genome, which is necessary to create daughter cells and precedes other cell division events.

The researchers were surprised by the findings. They had assumed that the spiroindolone, KAE609 (cipargamin), which is being investigated in clinical trials, killed parasites through a different mechanism. 

The investigators maintain that by understanding exactly how new drug candidates stop malaria, they will learn more about the parasite’s vulnerabilities and be able to determine the origin of drug resistance as soon as it arises. 

“We want to find the best ways to keep new drugs effective as long as we can,” Dr Vaidya said.

This study was funded by National Institutes of Health Grant R01-AI98413 and Medicines for Malaria Venture Grant MMV/08/0027.

Plasmodium parasite
invading an RBC
Credit: St Jude Children's
Research Hospital

Two new anti-malaria drug candidates with different mechanisms of action—a pyrazoleamide and a spiroindolone—promote an influx of sodium ions into Plasmodium parasites that have invaded red blood cells and multiply there.

Within minutes, the increase in sodium kills the parasites, investigators believe, by changing its outer membrane and promoting division before its genome has been replicated.

Akhil Vaidya, PhD, of Drexel University College of Medicine in Philadelphia, and members of the research team published details of their findings in PLOS Pathogens.

The Plasmodium plasma membrane contains very low levels of cholesterol, which is a major lipid component of most other cell membranes. 

Saponin, a detergent that can dissolve cholesterol-containing membranes, dissolves red blood cells infected by Plasmodium and releases intact parasites into the bloodstream. The detergent is unable to destroy the parasites because their membranes have low cholesterol content.

However, when researchers exposed the parasite cell membranes to the 2 drugs, they became permeable by saponin. The researchers deemed this to be a function of the increased amount of cholesterol incorporated into the parasite membrane.

“We believe that the cholesterol makes the parasite rigid, and then the parasite can no longer pass through very small spaces in the bloodstream,” Dr Vaidya said. The parasite cannot continue its lifecycle if it cannot enter red blood cells.

Researchers also discovered that when drug exposure is short, the changes in membrane composition are reversible. The parasites regain their resistance to saponin most likely because the additional membrane cholesterol washes off.

After 2 hours of treatment with either drug, many of the parasites had fragmented nuclei and interior membranes. Researchers did not observe any sign of multiplication of the parasite genome, which is necessary to create daughter cells and precedes other cell division events.

The researchers were surprised by the findings. They had assumed that the spiroindolone, KAE609 (cipargamin), which is being investigated in clinical trials, killed parasites through a different mechanism. 

The investigators maintain that by understanding exactly how new drug candidates stop malaria, they will learn more about the parasite’s vulnerabilities and be able to determine the origin of drug resistance as soon as it arises. 

“We want to find the best ways to keep new drugs effective as long as we can,” Dr Vaidya said.

This study was funded by National Institutes of Health Grant R01-AI98413 and Medicines for Malaria Venture Grant MMV/08/0027.

Plasmodium parasite
invading an RBC
Credit: St Jude Children's
Research Hospital

Two new anti-malaria drug candidates with different mechanisms of action—a pyrazoleamide and a spiroindolone—promote an influx of sodium ions into Plasmodium parasites that have invaded red blood cells and multiply there.

Within minutes, the increase in sodium kills the parasites, investigators believe, by changing its outer membrane and promoting division before its genome has been replicated.

Akhil Vaidya, PhD, of Drexel University College of Medicine in Philadelphia, and members of the research team published details of their findings in PLOS Pathogens.

The Plasmodium plasma membrane contains very low levels of cholesterol, which is a major lipid component of most other cell membranes. 

Saponin, a detergent that can dissolve cholesterol-containing membranes, dissolves red blood cells infected by Plasmodium and releases intact parasites into the bloodstream. The detergent is unable to destroy the parasites because their membranes have low cholesterol content.

However, when researchers exposed the parasite cell membranes to the 2 drugs, they became permeable by saponin. The researchers deemed this to be a function of the increased amount of cholesterol incorporated into the parasite membrane.

“We believe that the cholesterol makes the parasite rigid, and then the parasite can no longer pass through very small spaces in the bloodstream,” Dr Vaidya said. The parasite cannot continue its lifecycle if it cannot enter red blood cells.

Researchers also discovered that when drug exposure is short, the changes in membrane composition are reversible. The parasites regain their resistance to saponin most likely because the additional membrane cholesterol washes off.

After 2 hours of treatment with either drug, many of the parasites had fragmented nuclei and interior membranes. Researchers did not observe any sign of multiplication of the parasite genome, which is necessary to create daughter cells and precedes other cell division events.

The researchers were surprised by the findings. They had assumed that the spiroindolone, KAE609 (cipargamin), which is being investigated in clinical trials, killed parasites through a different mechanism. 

The investigators maintain that by understanding exactly how new drug candidates stop malaria, they will learn more about the parasite’s vulnerabilities and be able to determine the origin of drug resistance as soon as it arises. 

“We want to find the best ways to keep new drugs effective as long as we can,” Dr Vaidya said.

This study was funded by National Institutes of Health Grant R01-AI98413 and Medicines for Malaria Venture Grant MMV/08/0027.

Warfarin tablets

Using an Atrial Fibrillation Decision Support Tool (AFDST), investigators determined that 45% of women and 39% of men in the study population were not being treated according to the tool’s recommended treatments to prevent stroke resulting from atrial fibrillation (AF).

Investigators wanted to achieve a better understanding of the appropriateness of antithrombotic therapy for thromboprophylaxis in women and elderly adults.

So they studied a cohort of individuals with AF to determine whether they were treated according to recommendations.

According to lead author Mark Eckman, MD, of the University of Cincinnati in Ohio, under treatment of patients with AF is a national problem.

And ironically, “[W]omen have a higher risk of AF-related stroke,” he said, “controlling for other risk factors such as hypertension, diabetes, congestive heart failure, yet women are being under treated.”

The team retrospectively studied 1585 adults aged 28 to 93 with nonvalvular AF or flutter cared for in an ambulatory setting in the University of Cincinnati Health primary care network.

The primary care doctors were testing the computerized AFDST, which uses patient information and characteristics to help with decisions about anticoagulant therapy to prevent stroke in AF patients.

The AFDST calculates for the individual patient the risk of AF-related stroke and major bleeding while taking blood thinning therapy. Based on this information, the AFDST makes suggestions for the best treatment to prevent AF-related stroke.

Demographics

Of the 1585 study participants, 46% were women.

Half of the participants were receiving some form of oral anticoagulant, primarily warfarin (39%), 36% were on aspirin only, and 11% were receiving other oral anticoagulants.

The investigators noted a trend in the study population toward lower levels of oral anticoagulant use in women (48%) as compared to men (52%), but the trend was not statistically significant (P=0.06).

Results

The AFDST recommended oral anticoagulation for 87% of the participants, aspirin for 4%,  and no antithrombitic therapy for 9%.

Patients' antithrombotic therapy was concordant with the AFDST recommendation in 58% of the participants.

Of the 42% for whom therapy was discordant with the AFDST, 37% were receiving aspirin only or no antithrombotic therapy when the tool recommended oral anticoagulation; 2% were receiving no antithrombotic therapy when the tool recommended aspirin; and 3% were receiving aspirin or oral anticoagulation when the tool recommended no antithrombotic therapy.

And as mentioned above, current treatment was discordant from recommended treatment in 45% of women and 39% of men (P=0.02).

Forty-four percent of women were under treated, receiving aspirin only when oral anticoagulation was recommended, compared with 31% of men who were under treated (P<0.001). Women were 1.8 times as likely to be under treated as men.

"Doctors need to realize we have mental biases that women are healthier and at lower risk of stroke,” Dr Eckman said. 

“We think women are at lower risk and we ignore warning signs,” he continued. “Thus, when we are making decisions for blood thinning therapy for patients with atrial fibrillation, we need to remember that women are at higher risk and we need to make sure we treat them aggressively enough to prevent stroke."

Overall, the use of oral anticoagulants did not differ significantly by age, with 55% of the patients 85 years and older receiving anticoagulation and 49% of the patients younger than 85 receiving it (P=0.13).

In 35% of the older population, treatment was discordant with recommendations compared with 43% in the younger (P = 0.009). Similar proportions in the younger and older groups were undertreated (P=0.30).

According to investigators, one surprising finding was that the proportion of patients receiving discordant treatment was larger in the younger group than in the over-85 group. They attributed this largely to overtreatment in the 31 to 50 age group.

Dr Eckman and colleagues published these findings in Journal of the American Geriatrics Society.

The research was supported in part by grants from Bristol-Myers Squibb/Pfizer Education Consortium, Pfizer Medical Education Group, Informed Medical Decisions Foundation, and the National Institutes of Health/National Center for Advancing Translational Sciences.

Warfarin tablets

Using an Atrial Fibrillation Decision Support Tool (AFDST), investigators determined that 45% of women and 39% of men in the study population were not being treated according to the tool’s recommended treatments to prevent stroke resulting from atrial fibrillation (AF).

Investigators wanted to achieve a better understanding of the appropriateness of antithrombotic therapy for thromboprophylaxis in women and elderly adults.

So they studied a cohort of individuals with AF to determine whether they were treated according to recommendations.

According to lead author Mark Eckman, MD, of the University of Cincinnati in Ohio, under treatment of patients with AF is a national problem.

And ironically, “[W]omen have a higher risk of AF-related stroke,” he said, “controlling for other risk factors such as hypertension, diabetes, congestive heart failure, yet women are being under treated.”

The team retrospectively studied 1585 adults aged 28 to 93 with nonvalvular AF or flutter cared for in an ambulatory setting in the University of Cincinnati Health primary care network.

The primary care doctors were testing the computerized AFDST, which uses patient information and characteristics to help with decisions about anticoagulant therapy to prevent stroke in AF patients.

The AFDST calculates for the individual patient the risk of AF-related stroke and major bleeding while taking blood thinning therapy. Based on this information, the AFDST makes suggestions for the best treatment to prevent AF-related stroke.

Demographics

Of the 1585 study participants, 46% were women.

Half of the participants were receiving some form of oral anticoagulant, primarily warfarin (39%), 36% were on aspirin only, and 11% were receiving other oral anticoagulants.

The investigators noted a trend in the study population toward lower levels of oral anticoagulant use in women (48%) as compared to men (52%), but the trend was not statistically significant (P=0.06).

Results

The AFDST recommended oral anticoagulation for 87% of the participants, aspirin for 4%,  and no antithrombitic therapy for 9%.

Patients' antithrombotic therapy was concordant with the AFDST recommendation in 58% of the participants.

Of the 42% for whom therapy was discordant with the AFDST, 37% were receiving aspirin only or no antithrombotic therapy when the tool recommended oral anticoagulation; 2% were receiving no antithrombotic therapy when the tool recommended aspirin; and 3% were receiving aspirin or oral anticoagulation when the tool recommended no antithrombotic therapy.

And as mentioned above, current treatment was discordant from recommended treatment in 45% of women and 39% of men (P=0.02).

Forty-four percent of women were under treated, receiving aspirin only when oral anticoagulation was recommended, compared with 31% of men who were under treated (P<0.001). Women were 1.8 times as likely to be under treated as men.

"Doctors need to realize we have mental biases that women are healthier and at lower risk of stroke,” Dr Eckman said. 

“We think women are at lower risk and we ignore warning signs,” he continued. “Thus, when we are making decisions for blood thinning therapy for patients with atrial fibrillation, we need to remember that women are at higher risk and we need to make sure we treat them aggressively enough to prevent stroke."

Overall, the use of oral anticoagulants did not differ significantly by age, with 55% of the patients 85 years and older receiving anticoagulation and 49% of the patients younger than 85 receiving it (P=0.13).

In 35% of the older population, treatment was discordant with recommendations compared with 43% in the younger (P = 0.009). Similar proportions in the younger and older groups were undertreated (P=0.30).

According to investigators, one surprising finding was that the proportion of patients receiving discordant treatment was larger in the younger group than in the over-85 group. They attributed this largely to overtreatment in the 31 to 50 age group.

Dr Eckman and colleagues published these findings in Journal of the American Geriatrics Society.

The research was supported in part by grants from Bristol-Myers Squibb/Pfizer Education Consortium, Pfizer Medical Education Group, Informed Medical Decisions Foundation, and the National Institutes of Health/National Center for Advancing Translational Sciences.

Warfarin tablets

Using an Atrial Fibrillation Decision Support Tool (AFDST), investigators determined that 45% of women and 39% of men in the study population were not being treated according to the tool’s recommended treatments to prevent stroke resulting from atrial fibrillation (AF).

Investigators wanted to achieve a better understanding of the appropriateness of antithrombotic therapy for thromboprophylaxis in women and elderly adults.

So they studied a cohort of individuals with AF to determine whether they were treated according to recommendations.

According to lead author Mark Eckman, MD, of the University of Cincinnati in Ohio, under treatment of patients with AF is a national problem.

And ironically, “[W]omen have a higher risk of AF-related stroke,” he said, “controlling for other risk factors such as hypertension, diabetes, congestive heart failure, yet women are being under treated.”

The team retrospectively studied 1585 adults aged 28 to 93 with nonvalvular AF or flutter cared for in an ambulatory setting in the University of Cincinnati Health primary care network.

The primary care doctors were testing the computerized AFDST, which uses patient information and characteristics to help with decisions about anticoagulant therapy to prevent stroke in AF patients.

The AFDST calculates for the individual patient the risk of AF-related stroke and major bleeding while taking blood thinning therapy. Based on this information, the AFDST makes suggestions for the best treatment to prevent AF-related stroke.

Demographics

Of the 1585 study participants, 46% were women.

Half of the participants were receiving some form of oral anticoagulant, primarily warfarin (39%), 36% were on aspirin only, and 11% were receiving other oral anticoagulants.

The investigators noted a trend in the study population toward lower levels of oral anticoagulant use in women (48%) as compared to men (52%), but the trend was not statistically significant (P=0.06).

Results

The AFDST recommended oral anticoagulation for 87% of the participants, aspirin for 4%,  and no antithrombitic therapy for 9%.

Patients' antithrombotic therapy was concordant with the AFDST recommendation in 58% of the participants.

Of the 42% for whom therapy was discordant with the AFDST, 37% were receiving aspirin only or no antithrombotic therapy when the tool recommended oral anticoagulation; 2% were receiving no antithrombotic therapy when the tool recommended aspirin; and 3% were receiving aspirin or oral anticoagulation when the tool recommended no antithrombotic therapy.

And as mentioned above, current treatment was discordant from recommended treatment in 45% of women and 39% of men (P=0.02).

Forty-four percent of women were under treated, receiving aspirin only when oral anticoagulation was recommended, compared with 31% of men who were under treated (P<0.001). Women were 1.8 times as likely to be under treated as men.

"Doctors need to realize we have mental biases that women are healthier and at lower risk of stroke,” Dr Eckman said. 

“We think women are at lower risk and we ignore warning signs,” he continued. “Thus, when we are making decisions for blood thinning therapy for patients with atrial fibrillation, we need to remember that women are at higher risk and we need to make sure we treat them aggressively enough to prevent stroke."

Overall, the use of oral anticoagulants did not differ significantly by age, with 55% of the patients 85 years and older receiving anticoagulation and 49% of the patients younger than 85 receiving it (P=0.13).

In 35% of the older population, treatment was discordant with recommendations compared with 43% in the younger (P = 0.009). Similar proportions in the younger and older groups were undertreated (P=0.30).

According to investigators, one surprising finding was that the proportion of patients receiving discordant treatment was larger in the younger group than in the over-85 group. They attributed this largely to overtreatment in the 31 to 50 age group.

Dr Eckman and colleagues published these findings in Journal of the American Geriatrics Society.

The research was supported in part by grants from Bristol-Myers Squibb/Pfizer Education Consortium, Pfizer Medical Education Group, Informed Medical Decisions Foundation, and the National Institutes of Health/National Center for Advancing Translational Sciences.

Aspirin tablets

Photo credit: Jill Watson

Researchers say they may have found a new use for an ancient anti-inflammatory drug, salicylate, which was first described by the Greek physician Hippocrates.

“Salicylic acid is one of the oldest drugs on the planet,” said senior author Eric Verdin, MD, of the Gladstone Institutes/UCSF, “dating back to the Egyptians and the Greeks, but we're still discovering new things about it.”

Its derivatives, acetylsalicylic acid, or aspirin, and diflunisal suppress 2 key proteins, CREB-binding protein (CBP) and p300, which control levels of proteins that cause inflammation or are involved in cell growth.

By inhibiting p300 and CBP, salicylic acid and diflunisal block the activation of these proteins and prevent cellular damage caused by inflammation. The research team believes that both p300 and CBP can be targeted by drugs, which would have important clinical implications.

Earlier research conducted by coauthor Stephen D. Nimer, MD, of the University of Miami Miller School of Medicine in Florida, and colleagues found a link between p300 and the leukemia-promoting protein AML1-ETO.

In the current study, published in eLife, researchers tested whether suppressing p300 with diflunisal would suppress leukemia growth in mice.

The research team inoculated SCID mice with Kasumi-1 cells, an AML cell line with the t(8;21) translocation, which represents one of the subtypes of CBF leukemia.

Three weeks later, they started treating the mice with diflunisal. Diflunisal reduced tumor size in a dose-dependent manner, and after 3 weeks of treatment, the tumors were significantly smaller than in the vehicle-treated control mice.

In fact, the researchers noted most tumors disappeared in mice treated with higher doses of diflunisal. The researchers also pointed out that diflunisal, an FDA-approved drug containing a salicylic acid substructure, inhibited CBP/p300 more potently than salicylate.

The researchers concluded that diflunisal and salicylate have promise as an oral therapy for AML patients with a t(8;21) translocation, and called it “an exciting potential application” for this new characterization of older drugs.

“Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs,” Dr Verdin added.

The scientists are now pursuing a clinical trial to test whether salicylic acid can treat patients with leukemia as part of novel combination therapies.

Aspirin tablets

Photo credit: Jill Watson

Researchers say they may have found a new use for an ancient anti-inflammatory drug, salicylate, which was first described by the Greek physician Hippocrates.

“Salicylic acid is one of the oldest drugs on the planet,” said senior author Eric Verdin, MD, of the Gladstone Institutes/UCSF, “dating back to the Egyptians and the Greeks, but we're still discovering new things about it.”

Its derivatives, acetylsalicylic acid, or aspirin, and diflunisal suppress 2 key proteins, CREB-binding protein (CBP) and p300, which control levels of proteins that cause inflammation or are involved in cell growth.

By inhibiting p300 and CBP, salicylic acid and diflunisal block the activation of these proteins and prevent cellular damage caused by inflammation. The research team believes that both p300 and CBP can be targeted by drugs, which would have important clinical implications.

Earlier research conducted by coauthor Stephen D. Nimer, MD, of the University of Miami Miller School of Medicine in Florida, and colleagues found a link between p300 and the leukemia-promoting protein AML1-ETO.

In the current study, published in eLife, researchers tested whether suppressing p300 with diflunisal would suppress leukemia growth in mice.

The research team inoculated SCID mice with Kasumi-1 cells, an AML cell line with the t(8;21) translocation, which represents one of the subtypes of CBF leukemia.

Three weeks later, they started treating the mice with diflunisal. Diflunisal reduced tumor size in a dose-dependent manner, and after 3 weeks of treatment, the tumors were significantly smaller than in the vehicle-treated control mice.

In fact, the researchers noted most tumors disappeared in mice treated with higher doses of diflunisal. The researchers also pointed out that diflunisal, an FDA-approved drug containing a salicylic acid substructure, inhibited CBP/p300 more potently than salicylate.

The researchers concluded that diflunisal and salicylate have promise as an oral therapy for AML patients with a t(8;21) translocation, and called it “an exciting potential application” for this new characterization of older drugs.

“Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs,” Dr Verdin added.

The scientists are now pursuing a clinical trial to test whether salicylic acid can treat patients with leukemia as part of novel combination therapies.

Aspirin tablets

Photo credit: Jill Watson

Researchers say they may have found a new use for an ancient anti-inflammatory drug, salicylate, which was first described by the Greek physician Hippocrates.

“Salicylic acid is one of the oldest drugs on the planet,” said senior author Eric Verdin, MD, of the Gladstone Institutes/UCSF, “dating back to the Egyptians and the Greeks, but we're still discovering new things about it.”

Its derivatives, acetylsalicylic acid, or aspirin, and diflunisal suppress 2 key proteins, CREB-binding protein (CBP) and p300, which control levels of proteins that cause inflammation or are involved in cell growth.

By inhibiting p300 and CBP, salicylic acid and diflunisal block the activation of these proteins and prevent cellular damage caused by inflammation. The research team believes that both p300 and CBP can be targeted by drugs, which would have important clinical implications.

Earlier research conducted by coauthor Stephen D. Nimer, MD, of the University of Miami Miller School of Medicine in Florida, and colleagues found a link between p300 and the leukemia-promoting protein AML1-ETO.

In the current study, published in eLife, researchers tested whether suppressing p300 with diflunisal would suppress leukemia growth in mice.

The research team inoculated SCID mice with Kasumi-1 cells, an AML cell line with the t(8;21) translocation, which represents one of the subtypes of CBF leukemia.

Three weeks later, they started treating the mice with diflunisal. Diflunisal reduced tumor size in a dose-dependent manner, and after 3 weeks of treatment, the tumors were significantly smaller than in the vehicle-treated control mice.

In fact, the researchers noted most tumors disappeared in mice treated with higher doses of diflunisal. The researchers also pointed out that diflunisal, an FDA-approved drug containing a salicylic acid substructure, inhibited CBP/p300 more potently than salicylate.

The researchers concluded that diflunisal and salicylate have promise as an oral therapy for AML patients with a t(8;21) translocation, and called it “an exciting potential application” for this new characterization of older drugs.

“Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs,” Dr Verdin added.

The scientists are now pursuing a clinical trial to test whether salicylic acid can treat patients with leukemia as part of novel combination therapies.

Lab mouse

Using mouse models, researchers have developed a new cellular programming approach to create alloreactive T cells they say eliminate leukemic cells without causing graft-versus-host disease (GVHD).

They created the T cells using the donor key immune cell. When used in allogeneic hematopoietic stem cell transplantation and anti-leukemia therapy, the new approach reduced the toxicities that cause GVHD while preserving the anti-leukemia activity of the immune cell.

“This approach will be useful in the future when developing novel methods for immunotherapy,” said Yi Zhang, MD, PhD, of Temple University in Philadelphia, Pennsylvania.

Dr Zhang and colleagues took murine bone marrow using Flt3 ligand and Toll-like receptor agonists to produce δ-like ligand 4-positive dendritic cells (Dll4^hiDCs). When the dendritic cells were stimulated, CD4+ naïve T cells underwent effector differentiation and produced high levels of IFN-γ and IL-17 in vitro.

The team then transferred the allogeneic Dll4^hiDC-induced T cells into the mice. The cells did not induce severe GVHD and preserved anti-leukemic activity, “significantly improving the survival of leukemic mice undergoing allogeneic HSCT,” they said.

They noted that the IFN-γ was important for Dll4^hiDC programming in reducing the GVHD toxicities of alloreactive T cells. When the researchers transferred unstimulated T cells into mice, 5 of 8 mice died from GVHD and 3 of 8 died with tumor. Those that received Dll4^hiDC-induced T cells did not develop GVHD.

They also emphasized that this platform does not require transfection with viral vectors, which has limitations of safety and efficiency.

“This system will not only be useful for reducing GvHD,” Dr Zhang said, “but can also be used in the identification of T cells for the improvement of other types of immunotherapy for advanced cancer.”

The team published this research in Blood.

Lab mouse

Using mouse models, researchers have developed a new cellular programming approach to create alloreactive T cells they say eliminate leukemic cells without causing graft-versus-host disease (GVHD).

They created the T cells using the donor key immune cell. When used in allogeneic hematopoietic stem cell transplantation and anti-leukemia therapy, the new approach reduced the toxicities that cause GVHD while preserving the anti-leukemia activity of the immune cell.

“This approach will be useful in the future when developing novel methods for immunotherapy,” said Yi Zhang, MD, PhD, of Temple University in Philadelphia, Pennsylvania.

Dr Zhang and colleagues took murine bone marrow using Flt3 ligand and Toll-like receptor agonists to produce δ-like ligand 4-positive dendritic cells (Dll4^hiDCs). When the dendritic cells were stimulated, CD4+ naïve T cells underwent effector differentiation and produced high levels of IFN-γ and IL-17 in vitro.

The team then transferred the allogeneic Dll4^hiDC-induced T cells into the mice. The cells did not induce severe GVHD and preserved anti-leukemic activity, “significantly improving the survival of leukemic mice undergoing allogeneic HSCT,” they said.

They noted that the IFN-γ was important for Dll4^hiDC programming in reducing the GVHD toxicities of alloreactive T cells. When the researchers transferred unstimulated T cells into mice, 5 of 8 mice died from GVHD and 3 of 8 died with tumor. Those that received Dll4^hiDC-induced T cells did not develop GVHD.

They also emphasized that this platform does not require transfection with viral vectors, which has limitations of safety and efficiency.

“This system will not only be useful for reducing GvHD,” Dr Zhang said, “but can also be used in the identification of T cells for the improvement of other types of immunotherapy for advanced cancer.”

The team published this research in Blood.

Lab mouse

Using mouse models, researchers have developed a new cellular programming approach to create alloreactive T cells they say eliminate leukemic cells without causing graft-versus-host disease (GVHD).

They created the T cells using the donor key immune cell. When used in allogeneic hematopoietic stem cell transplantation and anti-leukemia therapy, the new approach reduced the toxicities that cause GVHD while preserving the anti-leukemia activity of the immune cell.

“This approach will be useful in the future when developing novel methods for immunotherapy,” said Yi Zhang, MD, PhD, of Temple University in Philadelphia, Pennsylvania.

Dr Zhang and colleagues took murine bone marrow using Flt3 ligand and Toll-like receptor agonists to produce δ-like ligand 4-positive dendritic cells (Dll4^hiDCs). When the dendritic cells were stimulated, CD4+ naïve T cells underwent effector differentiation and produced high levels of IFN-γ and IL-17 in vitro.

The team then transferred the allogeneic Dll4^hiDC-induced T cells into the mice. The cells did not induce severe GVHD and preserved anti-leukemic activity, “significantly improving the survival of leukemic mice undergoing allogeneic HSCT,” they said.

They noted that the IFN-γ was important for Dll4^hiDC programming in reducing the GVHD toxicities of alloreactive T cells. When the researchers transferred unstimulated T cells into mice, 5 of 8 mice died from GVHD and 3 of 8 died with tumor. Those that received Dll4^hiDC-induced T cells did not develop GVHD.

They also emphasized that this platform does not require transfection with viral vectors, which has limitations of safety and efficiency.

“This system will not only be useful for reducing GvHD,” Dr Zhang said, “but can also be used in the identification of T cells for the improvement of other types of immunotherapy for advanced cancer.”

The team published this research in Blood.

HSCs being prepared
for transplant
Photo credit: Chad McNeeley

Frailty among young adult hematopoietic cell transplant (HCT) survivors is high and approaches that of a community-based elderly population, according to results of the Bone Marrow Transplant Survivor Study.

Of the 998 HCT participants, frailty exceeded 8%, and they were 8.4 times more likely to be frail than their siblings.

Investigators defined frailty as exhibiting 3 or more of the following traits: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness.

Because HCT recipients are exposed to high-intensity chemotherapy, radiation, and immunosuppression at points before, during, and after transplant, the investigators set out to determine whether non-elderly HCT recipients who have survived 2 years or more after transplant were at a higher risk of frailty compared with a sibling comparator group.

Smita Bhatia, MD, of the University of Alabama at Birmingham, and colleagues conducted the study of HCT survivors between the ages of 18 and 64 and compared the results to a sibling control group. The authors also looked at the subsequent mortality of HCT survivors.

They reported their findings in JAMA Oncology.

The 998 HCT survivors who participated in the study received their transplants at City of Hope in Duarte, California, or at the University of Minnesota in Minneapolis, between 1974 and 1998. The survivors and the 297 siblings completed questionnaires between February 1999 and June 2005.

Demographics

The HCT survivors were a mean age of 42.5 years, and 911 (93%) had health insurance coverage.

This was comparable to the sibling controls, who were a mean age of 43.8 years (P=0.09) and 279 (95%) had health insurance coverage.

However, more siblings were female (64%), non-Hispanic white (88%), college graduates (56%), and 92% had annual household incomes of $20,000 or more.

In the HCT survivor group, 46% were female (P<0.001), 81% non-Hispanic white (P=0.004), 49% college graduates (P<0.001), and 80% had annual incomes of $20,000 or more (P<0.001).

HCT survivors were a mean age of 33.8 years when they had their transplants and the interval between HCT and participation in the study was 8.7 years.

Hematologic malignancies were the major diagnoses leading to HCT. Twenty-three percent had a primary diagnosis of chronic myeloid leukemia, 24% had acute myeloid leukemia, 19% had non-Hodgkin lymphoma, 10% had acute lymphoblastic leukemia, and 9% had Hodgkin lymphoma.

Seventy-seven percent of the HCT survivors had total body irradiation, and 300 of the 562 who received allogeneic transplants had chronic GVHD, with 24% of them reporting active GVHD at the time they participated in the study.

Frailty

Only 2 siblings (0.7%) considered themselves frail compared to 84 (8.4%) HCT survivors.

More survivors were underweight and reported low energy expenditure compared to the sibling group, but the differences were not statistically significant, P=0.26 and P=0.14, respectively.

However, significantly more survivors reported exhaustion (P<0.001), slowness (P<0.001), and weakness (P<0.001) compared to the sibling group,

The investigators then adjusted the data for age at study participation, sex, race/ethnicity, education, household income, health insurance, presence of grades 3 or 4 chronic health conditions, and transplant institution. They then found the HCT survivors to be 8.35 times more likely to be frail than their siblings (P=0.003).

HCT survivors with low annual incomes (P=0.03), less than a college education (P=0.002), with grades 3 or 4 chronic health conditions (P=0.02), with multiple myeloma (P=0.05), or with resolved chronic (P=0.04) or active chronic GVHD (P<0.001) were more likely to be frail compared to the other HCT survivors.

Mortality

The investigators followed the patients for a median of 10.3 years from the time participants completed the survey. At that time, 182 (18%) patients had died.

The 10-year cumulative all-cause mortality was 39.3% for patients with frailty and 14.7% for patients without frailty (P<0.001).

The 10-year cumulative relapse-related mortality was 15.5% among frail HCT patients and 4.5% for non-frail HCT patients.

And the 10-year cumulative non-relapse mortality was also higher among frail HCT recipients, 23.9% compared to 10.2% of the non-frail HCT recipients (P<0.001).

Multivariate analysis revealed that frailty was associated with a 2.76-fold increase in death. The variables included age at study participation, sex, presence of grades 3 to 4 chronic health conditions, primary diagnosis, annual household income, and risk of relapse at transplant. 

The investigators concluded that the therapies transplant patients undergo and post-transplant complications constitute a substantial stressor, placing HCT survivors at risk for frailty and premature aging.

“These findings demonstrate the need for interventions,” they added, “including personalized assessments and multidisciplinary efforts targeting both pre-frail and frail individuals to improve outcomes.”

HSCs being prepared
for transplant
Photo credit: Chad McNeeley

Frailty among young adult hematopoietic cell transplant (HCT) survivors is high and approaches that of a community-based elderly population, according to results of the Bone Marrow Transplant Survivor Study.

Of the 998 HCT participants, frailty exceeded 8%, and they were 8.4 times more likely to be frail than their siblings.

Investigators defined frailty as exhibiting 3 or more of the following traits: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness.

Because HCT recipients are exposed to high-intensity chemotherapy, radiation, and immunosuppression at points before, during, and after transplant, the investigators set out to determine whether non-elderly HCT recipients who have survived 2 years or more after transplant were at a higher risk of frailty compared with a sibling comparator group.

Smita Bhatia, MD, of the University of Alabama at Birmingham, and colleagues conducted the study of HCT survivors between the ages of 18 and 64 and compared the results to a sibling control group. The authors also looked at the subsequent mortality of HCT survivors.

They reported their findings in JAMA Oncology.

The 998 HCT survivors who participated in the study received their transplants at City of Hope in Duarte, California, or at the University of Minnesota in Minneapolis, between 1974 and 1998. The survivors and the 297 siblings completed questionnaires between February 1999 and June 2005.

Demographics

The HCT survivors were a mean age of 42.5 years, and 911 (93%) had health insurance coverage.

This was comparable to the sibling controls, who were a mean age of 43.8 years (P=0.09) and 279 (95%) had health insurance coverage.

However, more siblings were female (64%), non-Hispanic white (88%), college graduates (56%), and 92% had annual household incomes of $20,000 or more.

In the HCT survivor group, 46% were female (P<0.001), 81% non-Hispanic white (P=0.004), 49% college graduates (P<0.001), and 80% had annual incomes of $20,000 or more (P<0.001).

HCT survivors were a mean age of 33.8 years when they had their transplants and the interval between HCT and participation in the study was 8.7 years.

Hematologic malignancies were the major diagnoses leading to HCT. Twenty-three percent had a primary diagnosis of chronic myeloid leukemia, 24% had acute myeloid leukemia, 19% had non-Hodgkin lymphoma, 10% had acute lymphoblastic leukemia, and 9% had Hodgkin lymphoma.

Seventy-seven percent of the HCT survivors had total body irradiation, and 300 of the 562 who received allogeneic transplants had chronic GVHD, with 24% of them reporting active GVHD at the time they participated in the study.

Frailty

Only 2 siblings (0.7%) considered themselves frail compared to 84 (8.4%) HCT survivors.

More survivors were underweight and reported low energy expenditure compared to the sibling group, but the differences were not statistically significant, P=0.26 and P=0.14, respectively.

However, significantly more survivors reported exhaustion (P<0.001), slowness (P<0.001), and weakness (P<0.001) compared to the sibling group,

The investigators then adjusted the data for age at study participation, sex, race/ethnicity, education, household income, health insurance, presence of grades 3 or 4 chronic health conditions, and transplant institution. They then found the HCT survivors to be 8.35 times more likely to be frail than their siblings (P=0.003).

HCT survivors with low annual incomes (P=0.03), less than a college education (P=0.002), with grades 3 or 4 chronic health conditions (P=0.02), with multiple myeloma (P=0.05), or with resolved chronic (P=0.04) or active chronic GVHD (P<0.001) were more likely to be frail compared to the other HCT survivors.

Mortality

The investigators followed the patients for a median of 10.3 years from the time participants completed the survey. At that time, 182 (18%) patients had died.

The 10-year cumulative all-cause mortality was 39.3% for patients with frailty and 14.7% for patients without frailty (P<0.001).

The 10-year cumulative relapse-related mortality was 15.5% among frail HCT patients and 4.5% for non-frail HCT patients.

And the 10-year cumulative non-relapse mortality was also higher among frail HCT recipients, 23.9% compared to 10.2% of the non-frail HCT recipients (P<0.001).

Multivariate analysis revealed that frailty was associated with a 2.76-fold increase in death. The variables included age at study participation, sex, presence of grades 3 to 4 chronic health conditions, primary diagnosis, annual household income, and risk of relapse at transplant. 

The investigators concluded that the therapies transplant patients undergo and post-transplant complications constitute a substantial stressor, placing HCT survivors at risk for frailty and premature aging.

“These findings demonstrate the need for interventions,” they added, “including personalized assessments and multidisciplinary efforts targeting both pre-frail and frail individuals to improve outcomes.”

HSCs being prepared
for transplant
Photo credit: Chad McNeeley

Frailty among young adult hematopoietic cell transplant (HCT) survivors is high and approaches that of a community-based elderly population, according to results of the Bone Marrow Transplant Survivor Study.

Of the 998 HCT participants, frailty exceeded 8%, and they were 8.4 times more likely to be frail than their siblings.

Investigators defined frailty as exhibiting 3 or more of the following traits: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness.

Because HCT recipients are exposed to high-intensity chemotherapy, radiation, and immunosuppression at points before, during, and after transplant, the investigators set out to determine whether non-elderly HCT recipients who have survived 2 years or more after transplant were at a higher risk of frailty compared with a sibling comparator group.

Smita Bhatia, MD, of the University of Alabama at Birmingham, and colleagues conducted the study of HCT survivors between the ages of 18 and 64 and compared the results to a sibling control group. The authors also looked at the subsequent mortality of HCT survivors.

They reported their findings in JAMA Oncology.

The 998 HCT survivors who participated in the study received their transplants at City of Hope in Duarte, California, or at the University of Minnesota in Minneapolis, between 1974 and 1998. The survivors and the 297 siblings completed questionnaires between February 1999 and June 2005.

Demographics

The HCT survivors were a mean age of 42.5 years, and 911 (93%) had health insurance coverage.

This was comparable to the sibling controls, who were a mean age of 43.8 years (P=0.09) and 279 (95%) had health insurance coverage.

However, more siblings were female (64%), non-Hispanic white (88%), college graduates (56%), and 92% had annual household incomes of $20,000 or more.

In the HCT survivor group, 46% were female (P<0.001), 81% non-Hispanic white (P=0.004), 49% college graduates (P<0.001), and 80% had annual incomes of $20,000 or more (P<0.001).

HCT survivors were a mean age of 33.8 years when they had their transplants and the interval between HCT and participation in the study was 8.7 years.

Hematologic malignancies were the major diagnoses leading to HCT. Twenty-three percent had a primary diagnosis of chronic myeloid leukemia, 24% had acute myeloid leukemia, 19% had non-Hodgkin lymphoma, 10% had acute lymphoblastic leukemia, and 9% had Hodgkin lymphoma.

Seventy-seven percent of the HCT survivors had total body irradiation, and 300 of the 562 who received allogeneic transplants had chronic GVHD, with 24% of them reporting active GVHD at the time they participated in the study.

Frailty

Only 2 siblings (0.7%) considered themselves frail compared to 84 (8.4%) HCT survivors.

More survivors were underweight and reported low energy expenditure compared to the sibling group, but the differences were not statistically significant, P=0.26 and P=0.14, respectively.

However, significantly more survivors reported exhaustion (P<0.001), slowness (P<0.001), and weakness (P<0.001) compared to the sibling group,

The investigators then adjusted the data for age at study participation, sex, race/ethnicity, education, household income, health insurance, presence of grades 3 or 4 chronic health conditions, and transplant institution. They then found the HCT survivors to be 8.35 times more likely to be frail than their siblings (P=0.003).

HCT survivors with low annual incomes (P=0.03), less than a college education (P=0.002), with grades 3 or 4 chronic health conditions (P=0.02), with multiple myeloma (P=0.05), or with resolved chronic (P=0.04) or active chronic GVHD (P<0.001) were more likely to be frail compared to the other HCT survivors.

Mortality

The investigators followed the patients for a median of 10.3 years from the time participants completed the survey. At that time, 182 (18%) patients had died.

The 10-year cumulative all-cause mortality was 39.3% for patients with frailty and 14.7% for patients without frailty (P<0.001).

The 10-year cumulative relapse-related mortality was 15.5% among frail HCT patients and 4.5% for non-frail HCT patients.

And the 10-year cumulative non-relapse mortality was also higher among frail HCT recipients, 23.9% compared to 10.2% of the non-frail HCT recipients (P<0.001).

Multivariate analysis revealed that frailty was associated with a 2.76-fold increase in death. The variables included age at study participation, sex, presence of grades 3 to 4 chronic health conditions, primary diagnosis, annual household income, and risk of relapse at transplant. 

The investigators concluded that the therapies transplant patients undergo and post-transplant complications constitute a substantial stressor, placing HCT survivors at risk for frailty and premature aging.

“These findings demonstrate the need for interventions,” they added, “including personalized assessments and multidisciplinary efforts targeting both pre-frail and frail individuals to improve outcomes.”

Aedes aegypti mosquito
Photo courtesy of
Muhammad Mahdi Karim

Two compounds have shown activity against the Zika virus, according to Biotech Biotron, a company that develops compounds to fight viral diseases such as HIV and hepatitis C. The two compounds from its library killed the Zika virus in vitro, as determined by an independent USA laboratory facility.

“These early results are encouraging,” Michelle Miller, PhD, of Biotron, said. “Identification of these active compounds in our library is a starting point for designing potent drugs against Zika.”

At present, there is no approved vaccine or treatment for Zika virus, whose common symptoms include fever, rash, joint pain, and conjunctivitis.

While the symptoms are generally mild, Zika infection during pregnancy has been associated with microcephaly and other severe brain defects in the newborn.

In addition, Zika infection may be associated with an increased risk of Guillain-Barré syndrome, which is being investigated by the Centers for Disease Control and Prevention.

Biotron is planning to carry out more tests on the Zika virus to determine whether the compounds are likely to be safe and effective in humans.

The Zika virus is primarily spread by infected mosquitoes. But exposure to an infected person’s blood or other body fluids may also result in transmission.

Aedes aegypti mosquito
Photo courtesy of
Muhammad Mahdi Karim

Two compounds have shown activity against the Zika virus, according to Biotech Biotron, a company that develops compounds to fight viral diseases such as HIV and hepatitis C. The two compounds from its library killed the Zika virus in vitro, as determined by an independent USA laboratory facility.

“These early results are encouraging,” Michelle Miller, PhD, of Biotron, said. “Identification of these active compounds in our library is a starting point for designing potent drugs against Zika.”

At present, there is no approved vaccine or treatment for Zika virus, whose common symptoms include fever, rash, joint pain, and conjunctivitis.

While the symptoms are generally mild, Zika infection during pregnancy has been associated with microcephaly and other severe brain defects in the newborn.

In addition, Zika infection may be associated with an increased risk of Guillain-Barré syndrome, which is being investigated by the Centers for Disease Control and Prevention.

Biotron is planning to carry out more tests on the Zika virus to determine whether the compounds are likely to be safe and effective in humans.

The Zika virus is primarily spread by infected mosquitoes. But exposure to an infected person’s blood or other body fluids may also result in transmission.

Aedes aegypti mosquito
Photo courtesy of
Muhammad Mahdi Karim

Two compounds have shown activity against the Zika virus, according to Biotech Biotron, a company that develops compounds to fight viral diseases such as HIV and hepatitis C. The two compounds from its library killed the Zika virus in vitro, as determined by an independent USA laboratory facility.

“These early results are encouraging,” Michelle Miller, PhD, of Biotron, said. “Identification of these active compounds in our library is a starting point for designing potent drugs against Zika.”

At present, there is no approved vaccine or treatment for Zika virus, whose common symptoms include fever, rash, joint pain, and conjunctivitis.

While the symptoms are generally mild, Zika infection during pregnancy has been associated with microcephaly and other severe brain defects in the newborn.

In addition, Zika infection may be associated with an increased risk of Guillain-Barré syndrome, which is being investigated by the Centers for Disease Control and Prevention.

Biotron is planning to carry out more tests on the Zika virus to determine whether the compounds are likely to be safe and effective in humans.

The Zika virus is primarily spread by infected mosquitoes. But exposure to an infected person’s blood or other body fluids may also result in transmission.