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Novel agents hold promise for frontline AML treatment
Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.
But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”
Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”
Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”
Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”
Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”
As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”
Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”
This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.
Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.
But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”
Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”
Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”
Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”
Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”
As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”
Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”
This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.
Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.
But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”
Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”
Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”
Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”
Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”
As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”
Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”
This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.
FROM ALF 2020
COVID-19: Thromboembolic events high despite prophylaxis
in a new large observational U.S. study.
“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview.
“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.
However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.
The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
Rates similar to other very sick patients
The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.
“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”
He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”
Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.
“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.
“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.
The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.
“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”
For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White.
Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.
Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.
Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.
Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.
“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.
“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”
Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.
“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
ARDS biggest risk factor
Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.
“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”
They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.
“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.
“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.
The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
Wait for randomized trials
In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.
Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.
“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”
He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.
“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.
This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.
A version of this article originally appeared on Medscape.com.
in a new large observational U.S. study.
“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview.
“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.
However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.
The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
Rates similar to other very sick patients
The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.
“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”
He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”
Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.
“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.
“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.
The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.
“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”
For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White.
Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.
Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.
Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.
Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.
“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.
“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”
Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.
“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
ARDS biggest risk factor
Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.
“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”
They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.
“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.
“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.
The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
Wait for randomized trials
In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.
Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.
“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”
He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.
“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.
This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.
A version of this article originally appeared on Medscape.com.
in a new large observational U.S. study.
“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview.
“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.
However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.
The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
Rates similar to other very sick patients
The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.
“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”
He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”
Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.
“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.
“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.
The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.
“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”
For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White.
Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.
Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.
Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.
Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.
“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.
“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”
Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.
“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
ARDS biggest risk factor
Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.
“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”
They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.
“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.
“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.
The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
Wait for randomized trials
In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.
Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.
“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”
He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.
“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.
This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.
A version of this article originally appeared on Medscape.com.
Socioeconomic factors affect survival of multiple myeloma patients
Disparities driven by socioeconomic factors have been shown to affect outcomes for patients with a variety of cancer types. Researchers found that this was also true for patients with multiple myeloma, according to a report published in Hematology/Oncology and Stem Cell Therapy.
In particular, survival was affected by a variety of socioeconomic factors.
Researchers conducting the study queried the National Cancer Database for patients diagnosed with multiple myeloma between 2004 and 2016. Only those 56,102 patients who received systemic therapy as the first-line treatment were included, according to Thejus T. Jayakrishnan, MD, of Allegheny Health Network, Pittsburgh, and colleagues.
Enrollment rates for therapy were calculated using receiving systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator). The incident rate ratios were analyzed using Poisson regression. A multivariate Cox proportional hazards model was used for survival analysis of 50,543 patients, and differences were determined as hazard ratios.
Significant differences
The study showed that therapy enrollment was significantly affected by race and sex (P < .005), with the enrollment rate for women and for non-Hispanic Blacks both being lower versus men and non-Hispanic Whites, respectively.
Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were found to be associated with poor survival (HR >1), whereas being a woman or a non-Hispanic Black (who were speculated to have more favorable cytogenetic profiles), having a higher income, and having treatment at an academic center were all associated with improved survival (each category at HR <1).
“Disparities in [multiple myeloma] exist and are caused by a complex interplay of multiple factors, with socioeconomic factors such as insurance and income playing a dominant role. The disparities not only exact high human cost but also negatively impact the economics of health care,” the researchers concluded.
The study was not funded and the authors reported that they had no relevant disclosures.
SOURCE: Jayakrishnan TT et al. Hematol Oncol Stem Cell Ther. 2020 Oct 10. doi: 10.1016/j.hemonc.2020.09.005.
Disparities driven by socioeconomic factors have been shown to affect outcomes for patients with a variety of cancer types. Researchers found that this was also true for patients with multiple myeloma, according to a report published in Hematology/Oncology and Stem Cell Therapy.
In particular, survival was affected by a variety of socioeconomic factors.
Researchers conducting the study queried the National Cancer Database for patients diagnosed with multiple myeloma between 2004 and 2016. Only those 56,102 patients who received systemic therapy as the first-line treatment were included, according to Thejus T. Jayakrishnan, MD, of Allegheny Health Network, Pittsburgh, and colleagues.
Enrollment rates for therapy were calculated using receiving systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator). The incident rate ratios were analyzed using Poisson regression. A multivariate Cox proportional hazards model was used for survival analysis of 50,543 patients, and differences were determined as hazard ratios.
Significant differences
The study showed that therapy enrollment was significantly affected by race and sex (P < .005), with the enrollment rate for women and for non-Hispanic Blacks both being lower versus men and non-Hispanic Whites, respectively.
Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were found to be associated with poor survival (HR >1), whereas being a woman or a non-Hispanic Black (who were speculated to have more favorable cytogenetic profiles), having a higher income, and having treatment at an academic center were all associated with improved survival (each category at HR <1).
“Disparities in [multiple myeloma] exist and are caused by a complex interplay of multiple factors, with socioeconomic factors such as insurance and income playing a dominant role. The disparities not only exact high human cost but also negatively impact the economics of health care,” the researchers concluded.
The study was not funded and the authors reported that they had no relevant disclosures.
SOURCE: Jayakrishnan TT et al. Hematol Oncol Stem Cell Ther. 2020 Oct 10. doi: 10.1016/j.hemonc.2020.09.005.
Disparities driven by socioeconomic factors have been shown to affect outcomes for patients with a variety of cancer types. Researchers found that this was also true for patients with multiple myeloma, according to a report published in Hematology/Oncology and Stem Cell Therapy.
In particular, survival was affected by a variety of socioeconomic factors.
Researchers conducting the study queried the National Cancer Database for patients diagnosed with multiple myeloma between 2004 and 2016. Only those 56,102 patients who received systemic therapy as the first-line treatment were included, according to Thejus T. Jayakrishnan, MD, of Allegheny Health Network, Pittsburgh, and colleagues.
Enrollment rates for therapy were calculated using receiving systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator). The incident rate ratios were analyzed using Poisson regression. A multivariate Cox proportional hazards model was used for survival analysis of 50,543 patients, and differences were determined as hazard ratios.
Significant differences
The study showed that therapy enrollment was significantly affected by race and sex (P < .005), with the enrollment rate for women and for non-Hispanic Blacks both being lower versus men and non-Hispanic Whites, respectively.
Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were found to be associated with poor survival (HR >1), whereas being a woman or a non-Hispanic Black (who were speculated to have more favorable cytogenetic profiles), having a higher income, and having treatment at an academic center were all associated with improved survival (each category at HR <1).
“Disparities in [multiple myeloma] exist and are caused by a complex interplay of multiple factors, with socioeconomic factors such as insurance and income playing a dominant role. The disparities not only exact high human cost but also negatively impact the economics of health care,” the researchers concluded.
The study was not funded and the authors reported that they had no relevant disclosures.
SOURCE: Jayakrishnan TT et al. Hematol Oncol Stem Cell Ther. 2020 Oct 10. doi: 10.1016/j.hemonc.2020.09.005.
FROM HEMATOLOGY/ONCOLOGY AND STEM CELL THERAPY
Can AML patients be too old for cell transplantation?
How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.
“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.
As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”
Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”
Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”
Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.
OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.
His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).
Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”
How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”
However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.
SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.
How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.
“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.
As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”
Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”
Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”
Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.
OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.
His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).
Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”
How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”
However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.
SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.
How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.
“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.
As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”
Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”
Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”
Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.
OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.
His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).
Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”
How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”
However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.
SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.
FROM ALF 2020
Older age, r/r disease in lymphoma patients tied to increased COVID-19 death rate
Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.
Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.
These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.
The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
Promising results for many
There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.
With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.
The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).
Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.
“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.
The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.
SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.
Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.
Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.
These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.
The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
Promising results for many
There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.
With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.
The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).
Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.
“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.
The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.
SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.
Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.
Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.
These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.
The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
Promising results for many
There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.
With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.
The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).
Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.
“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.
The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.
SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.
FROM ECLINICALMEDICINE
Blood group O linked to decreased risk of SARS-CoV-2 infection
Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.
Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.
Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.
The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
Reduced prevalence
The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.
There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.
Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.
There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
Possible causes
The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.
“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.
One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.
SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.
Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.
Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.
Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.
The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
Reduced prevalence
The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.
There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.
Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.
There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
Possible causes
The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.
“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.
One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.
SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.
Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.
Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.
Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.
The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
Reduced prevalence
The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.
There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.
Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.
There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
Possible causes
The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.
“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.
One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.
SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.
FROM BLOOD ADVANCES
Study: Complications from childhood ALL and its treatment are common, but can be managed
Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.
In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.
The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
Survival and complications
Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.
In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).
In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).
During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.
“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.
Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.
In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.
The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
Survival and complications
Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.
In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).
In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).
During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.
“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.
Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.
In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.
The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
Survival and complications
Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.
In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).
In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).
During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.
“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.
FROM Clinical Lymphoma, Myeloma & Leukemia
Older adults with multiple myeloma face heavy burden of care
A substantial cumulative burden of treatment in the first year is borne by patients newly diagnosed with multiple myeloma (MM), according to a report published online in Clinical Lymphoma, Myeloma and Leukemia.
MM is a disease of aging, with a median age at diagnosis of 69 years, and the burden of treatment and not just possible outcomes should be considered in decision-making discussions with patients, according to researchers Hira S. Mian, MD, of McMaster University, Hamilton, Ont., and colleagues.
They performed a retrospective study of a Medicare-linked database of 3,065 adults newly diagnosed with multiple myeloma (MM) between 2007-2013. The treatment burden among the patients was assessed to determine those factors associated with high treatment burden.
Heavy burden
Treatment burden was defined as the number of total days with a health care encounter (including acute care and outpatient visits), oncology and nononcology physician visits, and the number of new prescriptions within the first year following diagnosis, according to the researchers.
The study found that there was a substantial burden of treatment, including a median of more than 2 months of cumulative interactions with health care, within the first year following diagnosis. This burden was highest during the first 3 months.
Those patients who had multiple comorbidities (adjusted odds ratio [aOR] 1.27 per 1-point increase in Charlson comorbidity index, P < .001), poor performance status (aOR 1.85, P < .001), myeloma-related end-organ damage, especially bone disease (aOR 2.28, P < .001), and those who received autologous stem cell transplant (aOR 2.41, P < .001) were more likely to have a higher treatment burden, they reported.
“Decision-making regarding treatment modalities should not just emphasize traditional parameters such as response rates and progression-free survival but should also include a discussion regarding the workload burden placed on the patient and the care partner, in order to ensure informed and patient-centered decision-making is prioritized. This may be particularly relevant among certain subgroups such as older patients with cancer who may prioritize quality of life over aggressive disease control and overall survival,” the researchers concluded.
The study was funded by the National Cancer Institute at the U.S. National Institutes of Health. The authors reported funding from a variety of pharmaceutical and biotechnology companies.
SOURCE: Mian HS et al. Clin Lymphoma Myeloma Leuk. 2020 Oct 1. doi: 10.1016/j.clml.2020.09.010.
A substantial cumulative burden of treatment in the first year is borne by patients newly diagnosed with multiple myeloma (MM), according to a report published online in Clinical Lymphoma, Myeloma and Leukemia.
MM is a disease of aging, with a median age at diagnosis of 69 years, and the burden of treatment and not just possible outcomes should be considered in decision-making discussions with patients, according to researchers Hira S. Mian, MD, of McMaster University, Hamilton, Ont., and colleagues.
They performed a retrospective study of a Medicare-linked database of 3,065 adults newly diagnosed with multiple myeloma (MM) between 2007-2013. The treatment burden among the patients was assessed to determine those factors associated with high treatment burden.
Heavy burden
Treatment burden was defined as the number of total days with a health care encounter (including acute care and outpatient visits), oncology and nononcology physician visits, and the number of new prescriptions within the first year following diagnosis, according to the researchers.
The study found that there was a substantial burden of treatment, including a median of more than 2 months of cumulative interactions with health care, within the first year following diagnosis. This burden was highest during the first 3 months.
Those patients who had multiple comorbidities (adjusted odds ratio [aOR] 1.27 per 1-point increase in Charlson comorbidity index, P < .001), poor performance status (aOR 1.85, P < .001), myeloma-related end-organ damage, especially bone disease (aOR 2.28, P < .001), and those who received autologous stem cell transplant (aOR 2.41, P < .001) were more likely to have a higher treatment burden, they reported.
“Decision-making regarding treatment modalities should not just emphasize traditional parameters such as response rates and progression-free survival but should also include a discussion regarding the workload burden placed on the patient and the care partner, in order to ensure informed and patient-centered decision-making is prioritized. This may be particularly relevant among certain subgroups such as older patients with cancer who may prioritize quality of life over aggressive disease control and overall survival,” the researchers concluded.
The study was funded by the National Cancer Institute at the U.S. National Institutes of Health. The authors reported funding from a variety of pharmaceutical and biotechnology companies.
SOURCE: Mian HS et al. Clin Lymphoma Myeloma Leuk. 2020 Oct 1. doi: 10.1016/j.clml.2020.09.010.
A substantial cumulative burden of treatment in the first year is borne by patients newly diagnosed with multiple myeloma (MM), according to a report published online in Clinical Lymphoma, Myeloma and Leukemia.
MM is a disease of aging, with a median age at diagnosis of 69 years, and the burden of treatment and not just possible outcomes should be considered in decision-making discussions with patients, according to researchers Hira S. Mian, MD, of McMaster University, Hamilton, Ont., and colleagues.
They performed a retrospective study of a Medicare-linked database of 3,065 adults newly diagnosed with multiple myeloma (MM) between 2007-2013. The treatment burden among the patients was assessed to determine those factors associated with high treatment burden.
Heavy burden
Treatment burden was defined as the number of total days with a health care encounter (including acute care and outpatient visits), oncology and nononcology physician visits, and the number of new prescriptions within the first year following diagnosis, according to the researchers.
The study found that there was a substantial burden of treatment, including a median of more than 2 months of cumulative interactions with health care, within the first year following diagnosis. This burden was highest during the first 3 months.
Those patients who had multiple comorbidities (adjusted odds ratio [aOR] 1.27 per 1-point increase in Charlson comorbidity index, P < .001), poor performance status (aOR 1.85, P < .001), myeloma-related end-organ damage, especially bone disease (aOR 2.28, P < .001), and those who received autologous stem cell transplant (aOR 2.41, P < .001) were more likely to have a higher treatment burden, they reported.
“Decision-making regarding treatment modalities should not just emphasize traditional parameters such as response rates and progression-free survival but should also include a discussion regarding the workload burden placed on the patient and the care partner, in order to ensure informed and patient-centered decision-making is prioritized. This may be particularly relevant among certain subgroups such as older patients with cancer who may prioritize quality of life over aggressive disease control and overall survival,” the researchers concluded.
The study was funded by the National Cancer Institute at the U.S. National Institutes of Health. The authors reported funding from a variety of pharmaceutical and biotechnology companies.
SOURCE: Mian HS et al. Clin Lymphoma Myeloma Leuk. 2020 Oct 1. doi: 10.1016/j.clml.2020.09.010.
FROM CLINICAL LYMPHOMA, MYELOMA AND LEUKEMIA
INR fails to predict bleeding in patients with cirrhosis
International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.
This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.
“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”
According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.
Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.
To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.
The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).
Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 109/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.
“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.
According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”
Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”
He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.
“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.
SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.
International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.
This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.
“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”
According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.
Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.
To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.
The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).
Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 109/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.
“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.
According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”
Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”
He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.
“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.
SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.
International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.
This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.
“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”
According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.
Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.
To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.
The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).
Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 109/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.
“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.
According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”
Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”
He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.
“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.
SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.
FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Landmark sickle cell report targets massive failures, calls for action
The National Academies of Science, Engineering, and Medicine have just released a 522-page report, but it’s not the usual compilation of guidelines for treatment of a disease. Instead, the authors of “Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action” argue in stark terms that the American society has colossally failed individuals living with sickle cell disease (SCD), who are mostly Black or Brown. A dramatic overhaul of the country’s medical and societal priorities is needed to turn things around to improve health and longevity among this rare disease population.
The findings from the NASEM report are explicit: “There has been substantial success in increasing the survival of children with SCD, but this success had not been translated to similar success as they become adults.” One factor posited to contribute to the slow progress in the improvement of quality and quantity of life for adults living with this disease is the fact that “SCD is largely a disease of African Americans, and as such exists in a context of racial discrimination, health and other societal disparities, mistrust of the health care system, and the effects of poverty.” The report also cites the substantial evidence that those with SCD may receive poorer quality of care.
The report’s 14 authors were made up of an ad hoc committee formed at the request of the Department of Health & Human Services’ Office of Minority Health. The office asked NASEM to convene the committee to develop a strategic plan and blueprint for the United States and others regarding SCD.
The NASEM SCD committee members “realized that we can’t address the medical components of SCD if we don’t explore societal issues and why it’s been so hard to get good care for people with sickle cell disease,” hematologist and report coauthor Ifeyinwa (Ify) Osunkwo, MD, professor of medicine and pediatrics at Atrium Health and director of the Sickle Cell Disease Enterprise, Levine Cancer Institute, Charlotte, N.C., said in an interview. Dr. Osunkwo is also the medical editor of Hematology News.
“After almost a year of meetings and digging into the background and history of SCD care, we came out with very comprehensive summary of where we were and where we want to be,” she said. “The report provides short-, intermediate- and long-term recommendations and identifies which entity and organization should be responsible for implementing them.”
The report authors, led by pediatrician and committee chair Marie Clare McCormick, MD, of the Harvard School of Public Health, Boston, stated that about 100,000 people in the United States and millions worldwide live with SCD. The disease kills more than 700 people per year in the United States, and treatment costs an estimated $2 billion a year.
When judged by disability-adjusted life-years lost – a measurement of expected healthy years of life without an illness – the impact of SCD on individuals is estimated to be greater than a long list of other diseases such as Alzheimer’s disease, breast cancer, type 1 diabetes, and AIDS/HIV, the report noted.
“The health care needs of individuals living with SCD have been neglected by the U.S. and global health care systems, causing them and their families to suffer,” the report said. “Many of the complications that afflict individuals with SCD, particularly pain, are invisible. Pain is only diagnosed by self-reports, and in SCD there are few to no external indicators of the pain experience. Nevertheless, the pain can be excruciatingly severe and requires treatment with strong analgesics.”
There’s even more misery to the story of SCD, the report said, and Dr. Osunkwo agreed. “It’s not just about pain. These individuals suffer from multiple organ-system complications that are physical but also psychological and societal. They experience a lot of disparities in every aspect of their lives. You’re sick, so then you can’t get a job or health insurance, you can’t get Social Security benefits. You can’t get the type of health care you need nor can you access the other forms of support you need and often you are judged as a drug seeker for complaining of pain or repeatedly seeking acute care for unresolved pain.”
Multiple factors exacerbate the experience of people living with SCD in America, the report said. “Because of systemic racism, unconscious bias, and the stigma associated with the diagnosis, the disease brings with it a much broader burden.”
Dr. Osunkwo put it this way: “SCD is a disease that mostly affects Brown and Black people, and that gets layered into the whole discrimination issues that Black and Brown people face compounding the health burden from their disease.”
The report added that “the SCD community has developed a significant lack of trust in the health care system due to the nearly universal stigma and lack of belief in their reports of pain, a lack of trust that has been further reinforced by historical events, such as the Tuskegee experiment.”
The report highlighted research that finds that Blacks “are more likely to receive a lower quality of pain management than white patients and may be perceived as having drug-seeking behavior.”
The report also identified gaps in treatment, noting that “many SCD complications are not restricted to any one organ system, and the impact of the disease on [quality of life] can be profound but hard to define and compartmentalize.”
Dr. Osunkwo said medical professionals often fail to understand the full breadth of the disease. “There’s no particular look to SCD. When you have cancer, you come in, and you look like you’re sick because you’re bald. Everyone clues into that cancer look and knows it’s lethal, that you’re may likely die early. We don’t have that “look that generates empathy” for SCD, and people don’t understand the burden on those affected. They don’t understand or appreciate that SCD shortens your lifespan as well ... that people living with SCD die 3 decades earlier than their ethnically matched peers. Also, SCD is associated with a lot of pain, and pain and the treatment of pain with opioids makes people [health care providers] uncomfortable unless it’s cancer pain.”
She added: “People also assume that, if it’s not pain, it’s not SCD even though SCD can cause leg ulcers and blood clots and even affect the tonsils, or lead to a stroke. When a disease complexity is too difficult for providers to understand, they either avoid it or don’t do anything for the patient.”
Screening and surveillance for SCD and sickle cell trait is insufficient, the report said, and the potential cost of missed childhood cases is large. Detecting the condition at birth allows the implementation of appropriate comprehensive care and treatment to prevent early death from infections and strokes. As the authors noted, “tremendous strides have been made in the past few decades in the care of children with SCD, which have led to almost all children in high-income settings surviving to adulthood.” However, there remains gaps in care coordination and follow-up of babies screened at birth and even bigger gaps in translating these life span gains to adults particularly around the period of transition from pediatrics to adult care when there appears to be a spike in morbidity and mortality.
The report summarized current treatments for SCD and noted “an influx of pipeline products” after years of little progress and identifies “a need for targeted SCD therapies that address the underlying cause of the disease.”
While treatment recommendations exist, Dr. Osunkwo said, “the evidence for them is very poor and many SCD complications have no evidence-based guidelines for providers to follow. We need more research to provide high quality evidence to make guidelines for SCD treatment stronger and more robust.”
In its final section, the report offers a “strategic plan and blueprint for sickle cell disease action.” It offers several strategies to achieve the vision of “long healthy productive lives for those living with sickle cell disease and sickle cell trait”:
- Establish and fund a research agenda to inform effective programs and policies across the life span.
- Implement efforts to advance understanding of the full impact of sickle cell trait on individuals and society.
- Address barriers to accessing current and pipeline therapies for SCD.
- Improve SCD awareness and strengthen advocacy efforts.
- Increase the number of qualified health professionals providing SCD care.
- Strengthen the evidence base for interventions and disease management and implement widespread efforts to monitor the quality of SCD care.
- Establish organized systems of care assuring both clinical and nonclinical supportive services to all persons living with SCD.
- Establish a national system to collect and link data to characterize the burden of disease, outcomes, and the needs of those with SCD across the life span.
“Right now, the average lifespan for SCD is in the mid-40s to mid-50s,” Dr. Osunkwo said. “That’s a horrible statistic. Even if we just take up half of these recommendations, people will live longer with SCD, and they’ll be more productive and contribute more to society. If we value a cancer life the same as a sickle cell life, we’ll be halfway across the finish line. But the stigma of SCD being a Black and Brown problem is going to be the hardest to confront as it requires a systemic change in our culture as a country and a health care system.”
Still, she said, the commissioning of the report “shows that there is a desire to understand the issue in better detail and try to mitigate it.”
Dr. Osunkwo and Dr. McCormick had no relevant disclosures.
SOURCE: National Academies of Sciences, Engineering, and Medicine. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, D.C.: National Academies Press, 2020.
The National Academies of Science, Engineering, and Medicine have just released a 522-page report, but it’s not the usual compilation of guidelines for treatment of a disease. Instead, the authors of “Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action” argue in stark terms that the American society has colossally failed individuals living with sickle cell disease (SCD), who are mostly Black or Brown. A dramatic overhaul of the country’s medical and societal priorities is needed to turn things around to improve health and longevity among this rare disease population.
The findings from the NASEM report are explicit: “There has been substantial success in increasing the survival of children with SCD, but this success had not been translated to similar success as they become adults.” One factor posited to contribute to the slow progress in the improvement of quality and quantity of life for adults living with this disease is the fact that “SCD is largely a disease of African Americans, and as such exists in a context of racial discrimination, health and other societal disparities, mistrust of the health care system, and the effects of poverty.” The report also cites the substantial evidence that those with SCD may receive poorer quality of care.
The report’s 14 authors were made up of an ad hoc committee formed at the request of the Department of Health & Human Services’ Office of Minority Health. The office asked NASEM to convene the committee to develop a strategic plan and blueprint for the United States and others regarding SCD.
The NASEM SCD committee members “realized that we can’t address the medical components of SCD if we don’t explore societal issues and why it’s been so hard to get good care for people with sickle cell disease,” hematologist and report coauthor Ifeyinwa (Ify) Osunkwo, MD, professor of medicine and pediatrics at Atrium Health and director of the Sickle Cell Disease Enterprise, Levine Cancer Institute, Charlotte, N.C., said in an interview. Dr. Osunkwo is also the medical editor of Hematology News.
“After almost a year of meetings and digging into the background and history of SCD care, we came out with very comprehensive summary of where we were and where we want to be,” she said. “The report provides short-, intermediate- and long-term recommendations and identifies which entity and organization should be responsible for implementing them.”
The report authors, led by pediatrician and committee chair Marie Clare McCormick, MD, of the Harvard School of Public Health, Boston, stated that about 100,000 people in the United States and millions worldwide live with SCD. The disease kills more than 700 people per year in the United States, and treatment costs an estimated $2 billion a year.
When judged by disability-adjusted life-years lost – a measurement of expected healthy years of life without an illness – the impact of SCD on individuals is estimated to be greater than a long list of other diseases such as Alzheimer’s disease, breast cancer, type 1 diabetes, and AIDS/HIV, the report noted.
“The health care needs of individuals living with SCD have been neglected by the U.S. and global health care systems, causing them and their families to suffer,” the report said. “Many of the complications that afflict individuals with SCD, particularly pain, are invisible. Pain is only diagnosed by self-reports, and in SCD there are few to no external indicators of the pain experience. Nevertheless, the pain can be excruciatingly severe and requires treatment with strong analgesics.”
There’s even more misery to the story of SCD, the report said, and Dr. Osunkwo agreed. “It’s not just about pain. These individuals suffer from multiple organ-system complications that are physical but also psychological and societal. They experience a lot of disparities in every aspect of their lives. You’re sick, so then you can’t get a job or health insurance, you can’t get Social Security benefits. You can’t get the type of health care you need nor can you access the other forms of support you need and often you are judged as a drug seeker for complaining of pain or repeatedly seeking acute care for unresolved pain.”
Multiple factors exacerbate the experience of people living with SCD in America, the report said. “Because of systemic racism, unconscious bias, and the stigma associated with the diagnosis, the disease brings with it a much broader burden.”
Dr. Osunkwo put it this way: “SCD is a disease that mostly affects Brown and Black people, and that gets layered into the whole discrimination issues that Black and Brown people face compounding the health burden from their disease.”
The report added that “the SCD community has developed a significant lack of trust in the health care system due to the nearly universal stigma and lack of belief in their reports of pain, a lack of trust that has been further reinforced by historical events, such as the Tuskegee experiment.”
The report highlighted research that finds that Blacks “are more likely to receive a lower quality of pain management than white patients and may be perceived as having drug-seeking behavior.”
The report also identified gaps in treatment, noting that “many SCD complications are not restricted to any one organ system, and the impact of the disease on [quality of life] can be profound but hard to define and compartmentalize.”
Dr. Osunkwo said medical professionals often fail to understand the full breadth of the disease. “There’s no particular look to SCD. When you have cancer, you come in, and you look like you’re sick because you’re bald. Everyone clues into that cancer look and knows it’s lethal, that you’re may likely die early. We don’t have that “look that generates empathy” for SCD, and people don’t understand the burden on those affected. They don’t understand or appreciate that SCD shortens your lifespan as well ... that people living with SCD die 3 decades earlier than their ethnically matched peers. Also, SCD is associated with a lot of pain, and pain and the treatment of pain with opioids makes people [health care providers] uncomfortable unless it’s cancer pain.”
She added: “People also assume that, if it’s not pain, it’s not SCD even though SCD can cause leg ulcers and blood clots and even affect the tonsils, or lead to a stroke. When a disease complexity is too difficult for providers to understand, they either avoid it or don’t do anything for the patient.”
Screening and surveillance for SCD and sickle cell trait is insufficient, the report said, and the potential cost of missed childhood cases is large. Detecting the condition at birth allows the implementation of appropriate comprehensive care and treatment to prevent early death from infections and strokes. As the authors noted, “tremendous strides have been made in the past few decades in the care of children with SCD, which have led to almost all children in high-income settings surviving to adulthood.” However, there remains gaps in care coordination and follow-up of babies screened at birth and even bigger gaps in translating these life span gains to adults particularly around the period of transition from pediatrics to adult care when there appears to be a spike in morbidity and mortality.
The report summarized current treatments for SCD and noted “an influx of pipeline products” after years of little progress and identifies “a need for targeted SCD therapies that address the underlying cause of the disease.”
While treatment recommendations exist, Dr. Osunkwo said, “the evidence for them is very poor and many SCD complications have no evidence-based guidelines for providers to follow. We need more research to provide high quality evidence to make guidelines for SCD treatment stronger and more robust.”
In its final section, the report offers a “strategic plan and blueprint for sickle cell disease action.” It offers several strategies to achieve the vision of “long healthy productive lives for those living with sickle cell disease and sickle cell trait”:
- Establish and fund a research agenda to inform effective programs and policies across the life span.
- Implement efforts to advance understanding of the full impact of sickle cell trait on individuals and society.
- Address barriers to accessing current and pipeline therapies for SCD.
- Improve SCD awareness and strengthen advocacy efforts.
- Increase the number of qualified health professionals providing SCD care.
- Strengthen the evidence base for interventions and disease management and implement widespread efforts to monitor the quality of SCD care.
- Establish organized systems of care assuring both clinical and nonclinical supportive services to all persons living with SCD.
- Establish a national system to collect and link data to characterize the burden of disease, outcomes, and the needs of those with SCD across the life span.
“Right now, the average lifespan for SCD is in the mid-40s to mid-50s,” Dr. Osunkwo said. “That’s a horrible statistic. Even if we just take up half of these recommendations, people will live longer with SCD, and they’ll be more productive and contribute more to society. If we value a cancer life the same as a sickle cell life, we’ll be halfway across the finish line. But the stigma of SCD being a Black and Brown problem is going to be the hardest to confront as it requires a systemic change in our culture as a country and a health care system.”
Still, she said, the commissioning of the report “shows that there is a desire to understand the issue in better detail and try to mitigate it.”
Dr. Osunkwo and Dr. McCormick had no relevant disclosures.
SOURCE: National Academies of Sciences, Engineering, and Medicine. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, D.C.: National Academies Press, 2020.
The National Academies of Science, Engineering, and Medicine have just released a 522-page report, but it’s not the usual compilation of guidelines for treatment of a disease. Instead, the authors of “Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action” argue in stark terms that the American society has colossally failed individuals living with sickle cell disease (SCD), who are mostly Black or Brown. A dramatic overhaul of the country’s medical and societal priorities is needed to turn things around to improve health and longevity among this rare disease population.
The findings from the NASEM report are explicit: “There has been substantial success in increasing the survival of children with SCD, but this success had not been translated to similar success as they become adults.” One factor posited to contribute to the slow progress in the improvement of quality and quantity of life for adults living with this disease is the fact that “SCD is largely a disease of African Americans, and as such exists in a context of racial discrimination, health and other societal disparities, mistrust of the health care system, and the effects of poverty.” The report also cites the substantial evidence that those with SCD may receive poorer quality of care.
The report’s 14 authors were made up of an ad hoc committee formed at the request of the Department of Health & Human Services’ Office of Minority Health. The office asked NASEM to convene the committee to develop a strategic plan and blueprint for the United States and others regarding SCD.
The NASEM SCD committee members “realized that we can’t address the medical components of SCD if we don’t explore societal issues and why it’s been so hard to get good care for people with sickle cell disease,” hematologist and report coauthor Ifeyinwa (Ify) Osunkwo, MD, professor of medicine and pediatrics at Atrium Health and director of the Sickle Cell Disease Enterprise, Levine Cancer Institute, Charlotte, N.C., said in an interview. Dr. Osunkwo is also the medical editor of Hematology News.
“After almost a year of meetings and digging into the background and history of SCD care, we came out with very comprehensive summary of where we were and where we want to be,” she said. “The report provides short-, intermediate- and long-term recommendations and identifies which entity and organization should be responsible for implementing them.”
The report authors, led by pediatrician and committee chair Marie Clare McCormick, MD, of the Harvard School of Public Health, Boston, stated that about 100,000 people in the United States and millions worldwide live with SCD. The disease kills more than 700 people per year in the United States, and treatment costs an estimated $2 billion a year.
When judged by disability-adjusted life-years lost – a measurement of expected healthy years of life without an illness – the impact of SCD on individuals is estimated to be greater than a long list of other diseases such as Alzheimer’s disease, breast cancer, type 1 diabetes, and AIDS/HIV, the report noted.
“The health care needs of individuals living with SCD have been neglected by the U.S. and global health care systems, causing them and their families to suffer,” the report said. “Many of the complications that afflict individuals with SCD, particularly pain, are invisible. Pain is only diagnosed by self-reports, and in SCD there are few to no external indicators of the pain experience. Nevertheless, the pain can be excruciatingly severe and requires treatment with strong analgesics.”
There’s even more misery to the story of SCD, the report said, and Dr. Osunkwo agreed. “It’s not just about pain. These individuals suffer from multiple organ-system complications that are physical but also psychological and societal. They experience a lot of disparities in every aspect of their lives. You’re sick, so then you can’t get a job or health insurance, you can’t get Social Security benefits. You can’t get the type of health care you need nor can you access the other forms of support you need and often you are judged as a drug seeker for complaining of pain or repeatedly seeking acute care for unresolved pain.”
Multiple factors exacerbate the experience of people living with SCD in America, the report said. “Because of systemic racism, unconscious bias, and the stigma associated with the diagnosis, the disease brings with it a much broader burden.”
Dr. Osunkwo put it this way: “SCD is a disease that mostly affects Brown and Black people, and that gets layered into the whole discrimination issues that Black and Brown people face compounding the health burden from their disease.”
The report added that “the SCD community has developed a significant lack of trust in the health care system due to the nearly universal stigma and lack of belief in their reports of pain, a lack of trust that has been further reinforced by historical events, such as the Tuskegee experiment.”
The report highlighted research that finds that Blacks “are more likely to receive a lower quality of pain management than white patients and may be perceived as having drug-seeking behavior.”
The report also identified gaps in treatment, noting that “many SCD complications are not restricted to any one organ system, and the impact of the disease on [quality of life] can be profound but hard to define and compartmentalize.”
Dr. Osunkwo said medical professionals often fail to understand the full breadth of the disease. “There’s no particular look to SCD. When you have cancer, you come in, and you look like you’re sick because you’re bald. Everyone clues into that cancer look and knows it’s lethal, that you’re may likely die early. We don’t have that “look that generates empathy” for SCD, and people don’t understand the burden on those affected. They don’t understand or appreciate that SCD shortens your lifespan as well ... that people living with SCD die 3 decades earlier than their ethnically matched peers. Also, SCD is associated with a lot of pain, and pain and the treatment of pain with opioids makes people [health care providers] uncomfortable unless it’s cancer pain.”
She added: “People also assume that, if it’s not pain, it’s not SCD even though SCD can cause leg ulcers and blood clots and even affect the tonsils, or lead to a stroke. When a disease complexity is too difficult for providers to understand, they either avoid it or don’t do anything for the patient.”
Screening and surveillance for SCD and sickle cell trait is insufficient, the report said, and the potential cost of missed childhood cases is large. Detecting the condition at birth allows the implementation of appropriate comprehensive care and treatment to prevent early death from infections and strokes. As the authors noted, “tremendous strides have been made in the past few decades in the care of children with SCD, which have led to almost all children in high-income settings surviving to adulthood.” However, there remains gaps in care coordination and follow-up of babies screened at birth and even bigger gaps in translating these life span gains to adults particularly around the period of transition from pediatrics to adult care when there appears to be a spike in morbidity and mortality.
The report summarized current treatments for SCD and noted “an influx of pipeline products” after years of little progress and identifies “a need for targeted SCD therapies that address the underlying cause of the disease.”
While treatment recommendations exist, Dr. Osunkwo said, “the evidence for them is very poor and many SCD complications have no evidence-based guidelines for providers to follow. We need more research to provide high quality evidence to make guidelines for SCD treatment stronger and more robust.”
In its final section, the report offers a “strategic plan and blueprint for sickle cell disease action.” It offers several strategies to achieve the vision of “long healthy productive lives for those living with sickle cell disease and sickle cell trait”:
- Establish and fund a research agenda to inform effective programs and policies across the life span.
- Implement efforts to advance understanding of the full impact of sickle cell trait on individuals and society.
- Address barriers to accessing current and pipeline therapies for SCD.
- Improve SCD awareness and strengthen advocacy efforts.
- Increase the number of qualified health professionals providing SCD care.
- Strengthen the evidence base for interventions and disease management and implement widespread efforts to monitor the quality of SCD care.
- Establish organized systems of care assuring both clinical and nonclinical supportive services to all persons living with SCD.
- Establish a national system to collect and link data to characterize the burden of disease, outcomes, and the needs of those with SCD across the life span.
“Right now, the average lifespan for SCD is in the mid-40s to mid-50s,” Dr. Osunkwo said. “That’s a horrible statistic. Even if we just take up half of these recommendations, people will live longer with SCD, and they’ll be more productive and contribute more to society. If we value a cancer life the same as a sickle cell life, we’ll be halfway across the finish line. But the stigma of SCD being a Black and Brown problem is going to be the hardest to confront as it requires a systemic change in our culture as a country and a health care system.”
Still, she said, the commissioning of the report “shows that there is a desire to understand the issue in better detail and try to mitigate it.”
Dr. Osunkwo and Dr. McCormick had no relevant disclosures.
SOURCE: National Academies of Sciences, Engineering, and Medicine. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, D.C.: National Academies Press, 2020.