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New ASH guideline: VTE prophylaxis after major surgery
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
EXPERT ANALYSIS FROM ASH 2019
Efficacy of postvenetoclax therapy may depend on prior agent exposure in CLL
ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.
If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.
If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.
“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”
The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.
All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.
“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.
While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.
“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.
Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.
“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.
They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.
In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.
PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.
However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.
Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”
Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.
SOURCE: Mato AR et al. ASH 2019, Abstract 502.
ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.
If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.
If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.
“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”
The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.
All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.
“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.
While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.
“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.
Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.
“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.
They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.
In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.
PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.
However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.
Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”
Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.
SOURCE: Mato AR et al. ASH 2019, Abstract 502.
ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.
If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.
If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.
“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”
The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.
All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.
“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.
While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.
“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.
Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.
“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.
They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.
In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.
PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.
However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.
Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”
Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.
SOURCE: Mato AR et al. ASH 2019, Abstract 502.
REPORTING FROM ASH 2019
Think twice: Choosing Wisely recommendations on testing to avoid in pediatric hematology
ORLANDO – There’s with some exceptions.
The list, which was produced by an expert panel with representatives from the American Society of Hematology and the American Society of Pediatric Hematology/Oncology (ASPHO), includes five tests or procedures that are considered unnecessary. The recommendations were released at the annual meeting of the American Society of Hematology.
The five recommendations are:
- Don’t perform routine preoperative hemostatic testing in an otherwise healthy child with no prior personal or family history of bleeding.
- Don’t transfuse platelets in a nonbleeding pediatric patient with a platelet count greater than 10,000/mcL, unless other signs of bleeding are present, or if the patient is set to undergo an invasive procedure.
- Don’t order thrombophilia testing on children with venous access-associated thrombosis in the absence of a positive family history.
- Don’t transfuse packed RBCs for iron-deficiency anemia in asymptomatic pediatric patients when there is no evidence of hemodynamic instability or active bleeding.
- Don’t routinely administer granulocyte colony–stimulating factor (G-CSF) for empiric treatment of pediatric patients with asymptomatic autoimmune neutropenia in the absence of recurrent or severe bacterial and/or fungal infections.
This is the third Choosing Wisely list produced by ASH. The group released the first list in 2013 and the second in 2014. But officials at both ASH and ASPHO have received feedback over the years that there should also be a pediatric-focused list in hematology, said Sarah O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and cochair of the expert panel that put together the recommendations.
Hemostatic testing
The panel recommended against preoperative hemostatic screening in healthy children with no personal or family history of excessive bleeding because the test does not effectively predict who will have unexpected surgical bleeding. The testing could instead identify artifacts or disorders unrelated to bleeding risk, such as factor XII deficiency or an infection-associated, transient lupus anticoagulant, according to Veronica H. Flood, MD, of the Medical College of Wisconsin, Milwaukee, and a member of the expert panel.
Performing this type of testing also adds cost and stress for families, and often delays surgery.
A look at the current literature reveals that there is little evidence to support coagulation testing in healthy children undergoing surgery. “Despite all this evidence, there remain practitioners who perform such screening on a regular basis,” Dr. Flood said.
For physicians concerned about bleeding risk, Dr. Flood said that existing guidelines support taking a bleeding history in preoperative patients. “This may take a little more time, but in the end will result in better results and less expense.”
Platelet transfusion
The panel recommended against platelet transfusion in nonbleeding pediatric patients with hypoproliferative thrombocytopenia and a platelet count greater than 10,000/mcL. The caveats for this recommendation are that it does not apply if there are other signs or symptoms of bleeding, if the patient is undergoing an invasive procedure, if the patient is aged 1 year or younger, or if the patient has immune-mediated thrombocytopenia, according to Rachel Bercovitz, MD, of the Ann & Robert H. Lurie Children’s Hospital of Chicago and a member of the expert panel.
Previous studies on the platelet transfusions in patients with hematologic malignancies have shown that 10,000/mcL is the appropriate threshold, with no difference in bleeding above that number and increased bleeding below it, Dr. Bercovitz said.
Additionally, while platelet transfusion is a safe procedure, Dr. Bercovitz said, it is not without acute and long-term risks.
Cost is also a factor. “Platelets are a limited and expensive resource,” she said.
Thrombophilia testing
Thrombophilia testing in children with a central venous catheter-associated thrombosis was once common practice but should be avoided, explained Leslie J. Raffini, MD, of the Children’s Hospital of Philadelphia and a member of the expert panel.
Thrombophilia does not influence the initial management of a first episode of provoked venous thrombosis, it does not inform the intensity of duration of anticoagulant therapy, and it does not predict recurrence of venous thrombosis in children, Dr. Raffini said.
In the 2013 Choosing Wisely list, ASH made the same recommendation against testing in adult patients with venous thromboembolism occurring in the setting of major transient risk factors. Thrombophilia testing is also expensive, often has to be repeated, and can be misinterpreted, Dr. Raffini said.
Packed RBC transfusion
The panel recommended against transfusion with packed RBCs for children with iron-deficiency anemia who have no symptoms and no evidence of hemodynamic instability or active bleeding. Transfusion is appropriate if children are symptomatic or are hemodynamically unstable, said Patrick T. McGann, MD, of Cincinnati Children’s Hospital and a member of the expert panel.
Rather than jump to transfusion, Dr. McGann said this group of asymptomatic and hemodynamically stable children should be treated for their iron deficiency through oral or intravenous iron. “This is not about ignoring iron deficiency.”
Both are effective treatments with multiple options available, he said. But sending a child to the hospital for transfusion is a costly option that is stressful for families and only provides a temporary solution to the issue, since treatment of the underlying iron deficiency still needs to be addressed, Dr. McGann said.
G-CSF treatment
The panel also recommended against routine administration of G-CSF in children with asymptomatic autoimmune neutropenia. Peter E. Newburger, MD, of Boston Children’s Hospital and a member of the expert guideline panel, said that there is limited evidence available and no published guidelines in this area, so the panel was guided by expert opinion.
In most cases, G-CSF is not necessary because autoimmune neutropenia resolves spontaneously by age 4-5 years and the risk of serious infection is extremely low. Appropriate management includes antibiotics for acute bacterial infection, good dental hygiene, and continued immunizations, Dr. Newburger said.
G-CSF may be appropriate in limited cases to improve quality of life, but it should be started at a low dose of 1-2 mcg/kg.
In cases of serious infection, Dr. Newburger said physicians should consider alternative diagnoses, such as congenital neutropenia or myelodysplastic syndromes.
ORLANDO – There’s with some exceptions.
The list, which was produced by an expert panel with representatives from the American Society of Hematology and the American Society of Pediatric Hematology/Oncology (ASPHO), includes five tests or procedures that are considered unnecessary. The recommendations were released at the annual meeting of the American Society of Hematology.
The five recommendations are:
- Don’t perform routine preoperative hemostatic testing in an otherwise healthy child with no prior personal or family history of bleeding.
- Don’t transfuse platelets in a nonbleeding pediatric patient with a platelet count greater than 10,000/mcL, unless other signs of bleeding are present, or if the patient is set to undergo an invasive procedure.
- Don’t order thrombophilia testing on children with venous access-associated thrombosis in the absence of a positive family history.
- Don’t transfuse packed RBCs for iron-deficiency anemia in asymptomatic pediatric patients when there is no evidence of hemodynamic instability or active bleeding.
- Don’t routinely administer granulocyte colony–stimulating factor (G-CSF) for empiric treatment of pediatric patients with asymptomatic autoimmune neutropenia in the absence of recurrent or severe bacterial and/or fungal infections.
This is the third Choosing Wisely list produced by ASH. The group released the first list in 2013 and the second in 2014. But officials at both ASH and ASPHO have received feedback over the years that there should also be a pediatric-focused list in hematology, said Sarah O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and cochair of the expert panel that put together the recommendations.
Hemostatic testing
The panel recommended against preoperative hemostatic screening in healthy children with no personal or family history of excessive bleeding because the test does not effectively predict who will have unexpected surgical bleeding. The testing could instead identify artifacts or disorders unrelated to bleeding risk, such as factor XII deficiency or an infection-associated, transient lupus anticoagulant, according to Veronica H. Flood, MD, of the Medical College of Wisconsin, Milwaukee, and a member of the expert panel.
Performing this type of testing also adds cost and stress for families, and often delays surgery.
A look at the current literature reveals that there is little evidence to support coagulation testing in healthy children undergoing surgery. “Despite all this evidence, there remain practitioners who perform such screening on a regular basis,” Dr. Flood said.
For physicians concerned about bleeding risk, Dr. Flood said that existing guidelines support taking a bleeding history in preoperative patients. “This may take a little more time, but in the end will result in better results and less expense.”
Platelet transfusion
The panel recommended against platelet transfusion in nonbleeding pediatric patients with hypoproliferative thrombocytopenia and a platelet count greater than 10,000/mcL. The caveats for this recommendation are that it does not apply if there are other signs or symptoms of bleeding, if the patient is undergoing an invasive procedure, if the patient is aged 1 year or younger, or if the patient has immune-mediated thrombocytopenia, according to Rachel Bercovitz, MD, of the Ann & Robert H. Lurie Children’s Hospital of Chicago and a member of the expert panel.
Previous studies on the platelet transfusions in patients with hematologic malignancies have shown that 10,000/mcL is the appropriate threshold, with no difference in bleeding above that number and increased bleeding below it, Dr. Bercovitz said.
Additionally, while platelet transfusion is a safe procedure, Dr. Bercovitz said, it is not without acute and long-term risks.
Cost is also a factor. “Platelets are a limited and expensive resource,” she said.
Thrombophilia testing
Thrombophilia testing in children with a central venous catheter-associated thrombosis was once common practice but should be avoided, explained Leslie J. Raffini, MD, of the Children’s Hospital of Philadelphia and a member of the expert panel.
Thrombophilia does not influence the initial management of a first episode of provoked venous thrombosis, it does not inform the intensity of duration of anticoagulant therapy, and it does not predict recurrence of venous thrombosis in children, Dr. Raffini said.
In the 2013 Choosing Wisely list, ASH made the same recommendation against testing in adult patients with venous thromboembolism occurring in the setting of major transient risk factors. Thrombophilia testing is also expensive, often has to be repeated, and can be misinterpreted, Dr. Raffini said.
Packed RBC transfusion
The panel recommended against transfusion with packed RBCs for children with iron-deficiency anemia who have no symptoms and no evidence of hemodynamic instability or active bleeding. Transfusion is appropriate if children are symptomatic or are hemodynamically unstable, said Patrick T. McGann, MD, of Cincinnati Children’s Hospital and a member of the expert panel.
Rather than jump to transfusion, Dr. McGann said this group of asymptomatic and hemodynamically stable children should be treated for their iron deficiency through oral or intravenous iron. “This is not about ignoring iron deficiency.”
Both are effective treatments with multiple options available, he said. But sending a child to the hospital for transfusion is a costly option that is stressful for families and only provides a temporary solution to the issue, since treatment of the underlying iron deficiency still needs to be addressed, Dr. McGann said.
G-CSF treatment
The panel also recommended against routine administration of G-CSF in children with asymptomatic autoimmune neutropenia. Peter E. Newburger, MD, of Boston Children’s Hospital and a member of the expert guideline panel, said that there is limited evidence available and no published guidelines in this area, so the panel was guided by expert opinion.
In most cases, G-CSF is not necessary because autoimmune neutropenia resolves spontaneously by age 4-5 years and the risk of serious infection is extremely low. Appropriate management includes antibiotics for acute bacterial infection, good dental hygiene, and continued immunizations, Dr. Newburger said.
G-CSF may be appropriate in limited cases to improve quality of life, but it should be started at a low dose of 1-2 mcg/kg.
In cases of serious infection, Dr. Newburger said physicians should consider alternative diagnoses, such as congenital neutropenia or myelodysplastic syndromes.
ORLANDO – There’s with some exceptions.
The list, which was produced by an expert panel with representatives from the American Society of Hematology and the American Society of Pediatric Hematology/Oncology (ASPHO), includes five tests or procedures that are considered unnecessary. The recommendations were released at the annual meeting of the American Society of Hematology.
The five recommendations are:
- Don’t perform routine preoperative hemostatic testing in an otherwise healthy child with no prior personal or family history of bleeding.
- Don’t transfuse platelets in a nonbleeding pediatric patient with a platelet count greater than 10,000/mcL, unless other signs of bleeding are present, or if the patient is set to undergo an invasive procedure.
- Don’t order thrombophilia testing on children with venous access-associated thrombosis in the absence of a positive family history.
- Don’t transfuse packed RBCs for iron-deficiency anemia in asymptomatic pediatric patients when there is no evidence of hemodynamic instability or active bleeding.
- Don’t routinely administer granulocyte colony–stimulating factor (G-CSF) for empiric treatment of pediatric patients with asymptomatic autoimmune neutropenia in the absence of recurrent or severe bacterial and/or fungal infections.
This is the third Choosing Wisely list produced by ASH. The group released the first list in 2013 and the second in 2014. But officials at both ASH and ASPHO have received feedback over the years that there should also be a pediatric-focused list in hematology, said Sarah O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and cochair of the expert panel that put together the recommendations.
Hemostatic testing
The panel recommended against preoperative hemostatic screening in healthy children with no personal or family history of excessive bleeding because the test does not effectively predict who will have unexpected surgical bleeding. The testing could instead identify artifacts or disorders unrelated to bleeding risk, such as factor XII deficiency or an infection-associated, transient lupus anticoagulant, according to Veronica H. Flood, MD, of the Medical College of Wisconsin, Milwaukee, and a member of the expert panel.
Performing this type of testing also adds cost and stress for families, and often delays surgery.
A look at the current literature reveals that there is little evidence to support coagulation testing in healthy children undergoing surgery. “Despite all this evidence, there remain practitioners who perform such screening on a regular basis,” Dr. Flood said.
For physicians concerned about bleeding risk, Dr. Flood said that existing guidelines support taking a bleeding history in preoperative patients. “This may take a little more time, but in the end will result in better results and less expense.”
Platelet transfusion
The panel recommended against platelet transfusion in nonbleeding pediatric patients with hypoproliferative thrombocytopenia and a platelet count greater than 10,000/mcL. The caveats for this recommendation are that it does not apply if there are other signs or symptoms of bleeding, if the patient is undergoing an invasive procedure, if the patient is aged 1 year or younger, or if the patient has immune-mediated thrombocytopenia, according to Rachel Bercovitz, MD, of the Ann & Robert H. Lurie Children’s Hospital of Chicago and a member of the expert panel.
Previous studies on the platelet transfusions in patients with hematologic malignancies have shown that 10,000/mcL is the appropriate threshold, with no difference in bleeding above that number and increased bleeding below it, Dr. Bercovitz said.
Additionally, while platelet transfusion is a safe procedure, Dr. Bercovitz said, it is not without acute and long-term risks.
Cost is also a factor. “Platelets are a limited and expensive resource,” she said.
Thrombophilia testing
Thrombophilia testing in children with a central venous catheter-associated thrombosis was once common practice but should be avoided, explained Leslie J. Raffini, MD, of the Children’s Hospital of Philadelphia and a member of the expert panel.
Thrombophilia does not influence the initial management of a first episode of provoked venous thrombosis, it does not inform the intensity of duration of anticoagulant therapy, and it does not predict recurrence of venous thrombosis in children, Dr. Raffini said.
In the 2013 Choosing Wisely list, ASH made the same recommendation against testing in adult patients with venous thromboembolism occurring in the setting of major transient risk factors. Thrombophilia testing is also expensive, often has to be repeated, and can be misinterpreted, Dr. Raffini said.
Packed RBC transfusion
The panel recommended against transfusion with packed RBCs for children with iron-deficiency anemia who have no symptoms and no evidence of hemodynamic instability or active bleeding. Transfusion is appropriate if children are symptomatic or are hemodynamically unstable, said Patrick T. McGann, MD, of Cincinnati Children’s Hospital and a member of the expert panel.
Rather than jump to transfusion, Dr. McGann said this group of asymptomatic and hemodynamically stable children should be treated for their iron deficiency through oral or intravenous iron. “This is not about ignoring iron deficiency.”
Both are effective treatments with multiple options available, he said. But sending a child to the hospital for transfusion is a costly option that is stressful for families and only provides a temporary solution to the issue, since treatment of the underlying iron deficiency still needs to be addressed, Dr. McGann said.
G-CSF treatment
The panel also recommended against routine administration of G-CSF in children with asymptomatic autoimmune neutropenia. Peter E. Newburger, MD, of Boston Children’s Hospital and a member of the expert guideline panel, said that there is limited evidence available and no published guidelines in this area, so the panel was guided by expert opinion.
In most cases, G-CSF is not necessary because autoimmune neutropenia resolves spontaneously by age 4-5 years and the risk of serious infection is extremely low. Appropriate management includes antibiotics for acute bacterial infection, good dental hygiene, and continued immunizations, Dr. Newburger said.
G-CSF may be appropriate in limited cases to improve quality of life, but it should be started at a low dose of 1-2 mcg/kg.
In cases of serious infection, Dr. Newburger said physicians should consider alternative diagnoses, such as congenital neutropenia or myelodysplastic syndromes.
REPORTING FROM ASH 2019
Oral arginine emerges as potential adjuvant for vaso-occlusive crisis management
ORLANDO – Oral arginine supplementation significantly increased plasma arginine levels and improved acute pain-related outcomes in Nigerian children with sickle cell disease in a randomized, placebo-controlled, phase 2 trial.
Of 68 children with a mean age of 10 years who were hospitalized with vaso-occlusive crisis involving severe pain and treated with standard pain management, 35 were randomized to receive adjuvant oral L-arginine at a dose of 100 mg/kg every 8 hours for 5 days or until discharge, and 33 received placebo. Those in the arginine arm experienced a 125% increase in their plasma arginine level, compared with a 29% increase in the placebo arm, Richard Onalo, FC Paed, reported during a press briefing at the annual meeting of the American Society of Hematology.
“This was statistically significant,” Dr. Onalo, of the department of pediatrics at the University of Abuja, Nigeria, said of the difference between the two arms. “Also, the global bioavailability ratio increased by 59% in the arginine arm.”
Low plasma arginine levels are associated with acute pain requiring hospitalization in Nigerian children with sickle cell disease, and have also been shown in a prior study in the United States to predict pediatric vaso-occlusion, Dr. Onalo said, adding that arginine supplementation, which has known opioid-sparing effects, was found in another phase 2, randomized, placebo-controlled U.S. study to significantly decrease pain scores.
In the current study, the increase in arginine bioavailability inversely correlated with Medication Quantification Scale scores, which were 73 vs. 120 in the arginine and placebo arms, respectively (r = -0.35; P = .02), indicating reduced analgesic use in the arginine arm, he said.
“Clinically, the patients in the arginine arm also tended to have a faster resolution in their pain score,” he said.
Despite similar baseline Numerical Pain Scale (PS) scores (8.7 and 8.4 on a 0-10 scale), day 5 pain scores were 1.2 vs. 2.0, and the mean daily rate of decline was 1.5 vs. 1.1 cm/day.
Crisis resolution was achieved by 25% of the patients in the arginine arm in about 72 hours, compared with about 120 hours in the placebo arms.
“By day 5, 54% of patients on arginine were already home, as compared with just 24% in the placebo arm, and this was found to be clinically and statistically significant,” Dr. Onalo said, noting that mean hospital length of stay was 110 hours vs. 156 hours in the arginine and placebo arms, respectively.
A non–statistically significant decrease in mean total opioid dose was also observed in the arginine vs. placebo arms (3.8 vs 5.1 mg/kg; P = .11).
Arginine supplementation in this study was safe; no serious treatment-related adverse events occurred, and there were no significant differences between the groups in the incidence of adverse events. Dr. Onalo noted, however, that a trend toward more vomiting was observed in the arginine versus the placebo arm (20% vs. 3%, P = .07).
Severe vaso-occlusive pain episodes are a major cause of morbidity and mortality in sickle cell disease, and based on the prior findings – and the lack of data regarding the role of arginine for treating acute sickle cell-related vaso-occlusive pain episodes in sub-Saharan Africa – Dr. Onalo and colleagues set out to assess its role in that setting.
“Also, we are interested in finding a molecule that can be used easily by the patient at home, and also can be [self-administered],” he said.
Children enrolled in the double-blind study had a severe vaso-occlusive pain episode, defined by a PS score of at least 7 on a scale of 0-10, at one of two major hospitals in Abuja, Nigeria. All patients received pain management, including opioid and nonopioid analgesics, per institutional practice.
The findings reinforce the role of arginine in vaso-occlusive pain episodes, and suggest that oral arginine is a promising adjuvant therapy for vaso-occlusive crisis management in patients with sickle cell disease, he said.
“We recommend a phase 3 multicenter clinical trial,” he added.
As for a potential role for arginine in this setting in the United States, prevention trials in the U.S. have thus far been negative, said Julie Panepinto, MD, the press briefing moderator and a pediatric hematologist-oncologist at Children’s Hospital of Wisconsin, Milwaukee.
“This is my first knowledge of use in the acute setting,” said Dr. Panepinto, also a professor at the Medical College of Wisconsin in Milwaukee. “There is going to be some future work looking at use of arginine in the U.S. for patients presenting with pain.”
For now, however, it’s too early to say that all patients should be started on arginine, she said, adding that more information is needed, including about appropriate dosing.
Nonetheless, it’s encouraging to see positive findings, she noted.
“We’ve been looking at and thinking about arginine for a long time, so I think this is a really exciting study ... that should lead us to future work to really understand better how to use the medication,” she said.
Dr. Onalo reported having no disclosures. Dr. Panepinto has received research funding from the National Institutes of Health and the Health Resources and Services Administration.
SOURCE: Onalo R et al. ASH 2019, Abstract 613.
ORLANDO – Oral arginine supplementation significantly increased plasma arginine levels and improved acute pain-related outcomes in Nigerian children with sickle cell disease in a randomized, placebo-controlled, phase 2 trial.
Of 68 children with a mean age of 10 years who were hospitalized with vaso-occlusive crisis involving severe pain and treated with standard pain management, 35 were randomized to receive adjuvant oral L-arginine at a dose of 100 mg/kg every 8 hours for 5 days or until discharge, and 33 received placebo. Those in the arginine arm experienced a 125% increase in their plasma arginine level, compared with a 29% increase in the placebo arm, Richard Onalo, FC Paed, reported during a press briefing at the annual meeting of the American Society of Hematology.
“This was statistically significant,” Dr. Onalo, of the department of pediatrics at the University of Abuja, Nigeria, said of the difference between the two arms. “Also, the global bioavailability ratio increased by 59% in the arginine arm.”
Low plasma arginine levels are associated with acute pain requiring hospitalization in Nigerian children with sickle cell disease, and have also been shown in a prior study in the United States to predict pediatric vaso-occlusion, Dr. Onalo said, adding that arginine supplementation, which has known opioid-sparing effects, was found in another phase 2, randomized, placebo-controlled U.S. study to significantly decrease pain scores.
In the current study, the increase in arginine bioavailability inversely correlated with Medication Quantification Scale scores, which were 73 vs. 120 in the arginine and placebo arms, respectively (r = -0.35; P = .02), indicating reduced analgesic use in the arginine arm, he said.
“Clinically, the patients in the arginine arm also tended to have a faster resolution in their pain score,” he said.
Despite similar baseline Numerical Pain Scale (PS) scores (8.7 and 8.4 on a 0-10 scale), day 5 pain scores were 1.2 vs. 2.0, and the mean daily rate of decline was 1.5 vs. 1.1 cm/day.
Crisis resolution was achieved by 25% of the patients in the arginine arm in about 72 hours, compared with about 120 hours in the placebo arms.
“By day 5, 54% of patients on arginine were already home, as compared with just 24% in the placebo arm, and this was found to be clinically and statistically significant,” Dr. Onalo said, noting that mean hospital length of stay was 110 hours vs. 156 hours in the arginine and placebo arms, respectively.
A non–statistically significant decrease in mean total opioid dose was also observed in the arginine vs. placebo arms (3.8 vs 5.1 mg/kg; P = .11).
Arginine supplementation in this study was safe; no serious treatment-related adverse events occurred, and there were no significant differences between the groups in the incidence of adverse events. Dr. Onalo noted, however, that a trend toward more vomiting was observed in the arginine versus the placebo arm (20% vs. 3%, P = .07).
Severe vaso-occlusive pain episodes are a major cause of morbidity and mortality in sickle cell disease, and based on the prior findings – and the lack of data regarding the role of arginine for treating acute sickle cell-related vaso-occlusive pain episodes in sub-Saharan Africa – Dr. Onalo and colleagues set out to assess its role in that setting.
“Also, we are interested in finding a molecule that can be used easily by the patient at home, and also can be [self-administered],” he said.
Children enrolled in the double-blind study had a severe vaso-occlusive pain episode, defined by a PS score of at least 7 on a scale of 0-10, at one of two major hospitals in Abuja, Nigeria. All patients received pain management, including opioid and nonopioid analgesics, per institutional practice.
The findings reinforce the role of arginine in vaso-occlusive pain episodes, and suggest that oral arginine is a promising adjuvant therapy for vaso-occlusive crisis management in patients with sickle cell disease, he said.
“We recommend a phase 3 multicenter clinical trial,” he added.
As for a potential role for arginine in this setting in the United States, prevention trials in the U.S. have thus far been negative, said Julie Panepinto, MD, the press briefing moderator and a pediatric hematologist-oncologist at Children’s Hospital of Wisconsin, Milwaukee.
“This is my first knowledge of use in the acute setting,” said Dr. Panepinto, also a professor at the Medical College of Wisconsin in Milwaukee. “There is going to be some future work looking at use of arginine in the U.S. for patients presenting with pain.”
For now, however, it’s too early to say that all patients should be started on arginine, she said, adding that more information is needed, including about appropriate dosing.
Nonetheless, it’s encouraging to see positive findings, she noted.
“We’ve been looking at and thinking about arginine for a long time, so I think this is a really exciting study ... that should lead us to future work to really understand better how to use the medication,” she said.
Dr. Onalo reported having no disclosures. Dr. Panepinto has received research funding from the National Institutes of Health and the Health Resources and Services Administration.
SOURCE: Onalo R et al. ASH 2019, Abstract 613.
ORLANDO – Oral arginine supplementation significantly increased plasma arginine levels and improved acute pain-related outcomes in Nigerian children with sickle cell disease in a randomized, placebo-controlled, phase 2 trial.
Of 68 children with a mean age of 10 years who were hospitalized with vaso-occlusive crisis involving severe pain and treated with standard pain management, 35 were randomized to receive adjuvant oral L-arginine at a dose of 100 mg/kg every 8 hours for 5 days or until discharge, and 33 received placebo. Those in the arginine arm experienced a 125% increase in their plasma arginine level, compared with a 29% increase in the placebo arm, Richard Onalo, FC Paed, reported during a press briefing at the annual meeting of the American Society of Hematology.
“This was statistically significant,” Dr. Onalo, of the department of pediatrics at the University of Abuja, Nigeria, said of the difference between the two arms. “Also, the global bioavailability ratio increased by 59% in the arginine arm.”
Low plasma arginine levels are associated with acute pain requiring hospitalization in Nigerian children with sickle cell disease, and have also been shown in a prior study in the United States to predict pediatric vaso-occlusion, Dr. Onalo said, adding that arginine supplementation, which has known opioid-sparing effects, was found in another phase 2, randomized, placebo-controlled U.S. study to significantly decrease pain scores.
In the current study, the increase in arginine bioavailability inversely correlated with Medication Quantification Scale scores, which were 73 vs. 120 in the arginine and placebo arms, respectively (r = -0.35; P = .02), indicating reduced analgesic use in the arginine arm, he said.
“Clinically, the patients in the arginine arm also tended to have a faster resolution in their pain score,” he said.
Despite similar baseline Numerical Pain Scale (PS) scores (8.7 and 8.4 on a 0-10 scale), day 5 pain scores were 1.2 vs. 2.0, and the mean daily rate of decline was 1.5 vs. 1.1 cm/day.
Crisis resolution was achieved by 25% of the patients in the arginine arm in about 72 hours, compared with about 120 hours in the placebo arms.
“By day 5, 54% of patients on arginine were already home, as compared with just 24% in the placebo arm, and this was found to be clinically and statistically significant,” Dr. Onalo said, noting that mean hospital length of stay was 110 hours vs. 156 hours in the arginine and placebo arms, respectively.
A non–statistically significant decrease in mean total opioid dose was also observed in the arginine vs. placebo arms (3.8 vs 5.1 mg/kg; P = .11).
Arginine supplementation in this study was safe; no serious treatment-related adverse events occurred, and there were no significant differences between the groups in the incidence of adverse events. Dr. Onalo noted, however, that a trend toward more vomiting was observed in the arginine versus the placebo arm (20% vs. 3%, P = .07).
Severe vaso-occlusive pain episodes are a major cause of morbidity and mortality in sickle cell disease, and based on the prior findings – and the lack of data regarding the role of arginine for treating acute sickle cell-related vaso-occlusive pain episodes in sub-Saharan Africa – Dr. Onalo and colleagues set out to assess its role in that setting.
“Also, we are interested in finding a molecule that can be used easily by the patient at home, and also can be [self-administered],” he said.
Children enrolled in the double-blind study had a severe vaso-occlusive pain episode, defined by a PS score of at least 7 on a scale of 0-10, at one of two major hospitals in Abuja, Nigeria. All patients received pain management, including opioid and nonopioid analgesics, per institutional practice.
The findings reinforce the role of arginine in vaso-occlusive pain episodes, and suggest that oral arginine is a promising adjuvant therapy for vaso-occlusive crisis management in patients with sickle cell disease, he said.
“We recommend a phase 3 multicenter clinical trial,” he added.
As for a potential role for arginine in this setting in the United States, prevention trials in the U.S. have thus far been negative, said Julie Panepinto, MD, the press briefing moderator and a pediatric hematologist-oncologist at Children’s Hospital of Wisconsin, Milwaukee.
“This is my first knowledge of use in the acute setting,” said Dr. Panepinto, also a professor at the Medical College of Wisconsin in Milwaukee. “There is going to be some future work looking at use of arginine in the U.S. for patients presenting with pain.”
For now, however, it’s too early to say that all patients should be started on arginine, she said, adding that more information is needed, including about appropriate dosing.
Nonetheless, it’s encouraging to see positive findings, she noted.
“We’ve been looking at and thinking about arginine for a long time, so I think this is a really exciting study ... that should lead us to future work to really understand better how to use the medication,” she said.
Dr. Onalo reported having no disclosures. Dr. Panepinto has received research funding from the National Institutes of Health and the Health Resources and Services Administration.
SOURCE: Onalo R et al. ASH 2019, Abstract 613.
REPORTING FROM ASH 2019
NFIX could be a target for sickle cell therapy
ORLANDO – Preclinical research suggests nuclear factor I X is a fetal hemoglobin repressor, a finding that could have implications for the treatment of sickle cell disease.
Researchers found that knocking down nuclear factor I X (NFIX) in adult erythroblasts induced fetal hemoglobin expression in a vast majority of cells, and the total amount of fetal hemoglobin in those cells was about 40%. The target level of fetal hemoglobin for sickle cell patients to become asymptomatic is 30%, according to study investigator Jeffrey R. Shearstone, PhD, of Syros Pharmaceuticals in Cambridge, Mass. He made these remarks during a press conference at the annual meeting of the American Society of Hematology. Mudit Chaand, PhD, also of Syros, is scheduled to present the study at the meeting on Dec. 9, 2019.
“While this is obviously a preclinical, investigational study, to see levels of induction in primary cells and cell lines of 40% is very encouraging and shows that [NFIX] is a very potent fetal hemoglobin repressor,” Dr. Shearstone said. “We see this discovery as, potentially, a new avenue for therapeutic intervention in sickle cell disease, but there’s still a lot of work to be done.”
Syros researchers began this study by comparing erythroblasts derived from cord blood, which have high levels of fetal hemoglobin, and erythroblasts derived from bone marrow, which have low levels of fetal hemoglobin. The team’s goal was to identify transcription factors that might regulate the repression of fetal hemoglobin in adult cells.
Chromatin accessibility mapping pointed to NFIX as a hemoglobin repressor. The researchers observed increased accessibility at the NFIX promoter and elevated NFIX messenger RNA in adult cells.
To confirm NFIX’s role as a repressor of fetal hemoglobin, the researchers used short hairpin RNA to knock down NFIX in primary erythroblasts and cell lines.
“By knocking down NFIX, we saw a very robust induction of fetal hemoglobin,” Dr. Shearstone said. “We saw nearly 100% of cells in which NFIX was knocked down express fetal hemoglobin. This level of induction compared very favorably to probably the two most potent known repressors of fetal hemoglobin, ZBTB7A and BCL11A.”
Specifically, 86%-97% of cells with NFIX knockdown expressed fetal hemoglobin, compared with 16% of control cells, 88% of cells with BCL11A knockdown, and 91% of cells with ZBTB7A knockdown.
The total amount of fetal hemoglobin in erythroblasts with NFIX knockdown was 39%-40%.
The researchers plan to conduct additional studies to validate these results, examine how NFIX directly binds at the fetal globin promoter, determine if NFIX interacts with any previously identified fetal hemoglobin repressors, and investigate how NFIX can be shut down in patients with sickle cell disease. The researchers’ ultimate goal is to develop a small molecule that would target NFIX.
All researchers involved in this work are employees of Syros Pharmaceuticals.
SOURCE: Shearstone JR et al. ASH 2019, Abstract 821.
ORLANDO – Preclinical research suggests nuclear factor I X is a fetal hemoglobin repressor, a finding that could have implications for the treatment of sickle cell disease.
Researchers found that knocking down nuclear factor I X (NFIX) in adult erythroblasts induced fetal hemoglobin expression in a vast majority of cells, and the total amount of fetal hemoglobin in those cells was about 40%. The target level of fetal hemoglobin for sickle cell patients to become asymptomatic is 30%, according to study investigator Jeffrey R. Shearstone, PhD, of Syros Pharmaceuticals in Cambridge, Mass. He made these remarks during a press conference at the annual meeting of the American Society of Hematology. Mudit Chaand, PhD, also of Syros, is scheduled to present the study at the meeting on Dec. 9, 2019.
“While this is obviously a preclinical, investigational study, to see levels of induction in primary cells and cell lines of 40% is very encouraging and shows that [NFIX] is a very potent fetal hemoglobin repressor,” Dr. Shearstone said. “We see this discovery as, potentially, a new avenue for therapeutic intervention in sickle cell disease, but there’s still a lot of work to be done.”
Syros researchers began this study by comparing erythroblasts derived from cord blood, which have high levels of fetal hemoglobin, and erythroblasts derived from bone marrow, which have low levels of fetal hemoglobin. The team’s goal was to identify transcription factors that might regulate the repression of fetal hemoglobin in adult cells.
Chromatin accessibility mapping pointed to NFIX as a hemoglobin repressor. The researchers observed increased accessibility at the NFIX promoter and elevated NFIX messenger RNA in adult cells.
To confirm NFIX’s role as a repressor of fetal hemoglobin, the researchers used short hairpin RNA to knock down NFIX in primary erythroblasts and cell lines.
“By knocking down NFIX, we saw a very robust induction of fetal hemoglobin,” Dr. Shearstone said. “We saw nearly 100% of cells in which NFIX was knocked down express fetal hemoglobin. This level of induction compared very favorably to probably the two most potent known repressors of fetal hemoglobin, ZBTB7A and BCL11A.”
Specifically, 86%-97% of cells with NFIX knockdown expressed fetal hemoglobin, compared with 16% of control cells, 88% of cells with BCL11A knockdown, and 91% of cells with ZBTB7A knockdown.
The total amount of fetal hemoglobin in erythroblasts with NFIX knockdown was 39%-40%.
The researchers plan to conduct additional studies to validate these results, examine how NFIX directly binds at the fetal globin promoter, determine if NFIX interacts with any previously identified fetal hemoglobin repressors, and investigate how NFIX can be shut down in patients with sickle cell disease. The researchers’ ultimate goal is to develop a small molecule that would target NFIX.
All researchers involved in this work are employees of Syros Pharmaceuticals.
SOURCE: Shearstone JR et al. ASH 2019, Abstract 821.
ORLANDO – Preclinical research suggests nuclear factor I X is a fetal hemoglobin repressor, a finding that could have implications for the treatment of sickle cell disease.
Researchers found that knocking down nuclear factor I X (NFIX) in adult erythroblasts induced fetal hemoglobin expression in a vast majority of cells, and the total amount of fetal hemoglobin in those cells was about 40%. The target level of fetal hemoglobin for sickle cell patients to become asymptomatic is 30%, according to study investigator Jeffrey R. Shearstone, PhD, of Syros Pharmaceuticals in Cambridge, Mass. He made these remarks during a press conference at the annual meeting of the American Society of Hematology. Mudit Chaand, PhD, also of Syros, is scheduled to present the study at the meeting on Dec. 9, 2019.
“While this is obviously a preclinical, investigational study, to see levels of induction in primary cells and cell lines of 40% is very encouraging and shows that [NFIX] is a very potent fetal hemoglobin repressor,” Dr. Shearstone said. “We see this discovery as, potentially, a new avenue for therapeutic intervention in sickle cell disease, but there’s still a lot of work to be done.”
Syros researchers began this study by comparing erythroblasts derived from cord blood, which have high levels of fetal hemoglobin, and erythroblasts derived from bone marrow, which have low levels of fetal hemoglobin. The team’s goal was to identify transcription factors that might regulate the repression of fetal hemoglobin in adult cells.
Chromatin accessibility mapping pointed to NFIX as a hemoglobin repressor. The researchers observed increased accessibility at the NFIX promoter and elevated NFIX messenger RNA in adult cells.
To confirm NFIX’s role as a repressor of fetal hemoglobin, the researchers used short hairpin RNA to knock down NFIX in primary erythroblasts and cell lines.
“By knocking down NFIX, we saw a very robust induction of fetal hemoglobin,” Dr. Shearstone said. “We saw nearly 100% of cells in which NFIX was knocked down express fetal hemoglobin. This level of induction compared very favorably to probably the two most potent known repressors of fetal hemoglobin, ZBTB7A and BCL11A.”
Specifically, 86%-97% of cells with NFIX knockdown expressed fetal hemoglobin, compared with 16% of control cells, 88% of cells with BCL11A knockdown, and 91% of cells with ZBTB7A knockdown.
The total amount of fetal hemoglobin in erythroblasts with NFIX knockdown was 39%-40%.
The researchers plan to conduct additional studies to validate these results, examine how NFIX directly binds at the fetal globin promoter, determine if NFIX interacts with any previously identified fetal hemoglobin repressors, and investigate how NFIX can be shut down in patients with sickle cell disease. The researchers’ ultimate goal is to develop a small molecule that would target NFIX.
All researchers involved in this work are employees of Syros Pharmaceuticals.
SOURCE: Shearstone JR et al. ASH 2019, Abstract 821.
REPORTING FROM ASH 2019
Study halted; ‘hyperprogression’ seen with nivolumab for R/R PTCL
ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.
An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.
“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.
The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.
They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.
Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.
The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.
All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.
As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.
The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.
“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.
Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.
The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.
“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.
“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.
“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.
The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.
SOURCE: Bennani NN et al. ASH 2019, Abstract 467.
ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.
An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.
“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.
The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.
They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.
Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.
The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.
All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.
As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.
The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.
“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.
Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.
The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.
“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.
“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.
“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.
The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.
SOURCE: Bennani NN et al. ASH 2019, Abstract 467.
ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.
An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.
“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.
The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.
They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.
Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.
The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.
All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.
As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.
The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.
“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.
Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.
The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.
“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.
“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.
“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.
The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.
SOURCE: Bennani NN et al. ASH 2019, Abstract 467.
REPORTING FROM ASH 2019
Fragmentation of sickle cell disease care starts in young adulthood
ORLANDO – While over time, results of a retrospective study suggest.
Nearly 60% of children between aged10-17 years were seen at just one facility over the course of 7 years in the analysis, which was based on analysis of data for nearly 7,000 patients seen in California during 1991-2016.
That contrasted sharply with young adults, aged 18-25 years, only about 20% of whom were admitted to one facility, said senior study author Anjlee Mahajan, MD, of the University of California, Davis, adding that another 20% were seen at five or more centers over a 7-year follow-up period.
Fragmentation of care didn’t increase the risk of death in this study, as investigators hypothesized it might. However, the outcomes and the quality of care among young adults with SCD who received inpatient care at multiple facilities nevertheless was likely to be affected, Dr. Mahajan said at the annual meeting of the American Society of Hematology.
“Imagine what that would be like to have a chronic, debilitating illness and to have to go to multiple different hospitals, during this vulnerable time period in your life, and being seen by different care providers who may not know you and may not have all of your records as well,” she said in a press conference at the meeting.
Providers and the health care system need to work harder to ensure young adults receive comprehensive and coordinated care, especially at a time when therapeutic advances are improving the treatment of this disease, according to the investigator.
“When you’re seen at one center, you can have a specific pain plan, and maybe when you are going into the emergency room and being admitted, your sickle cell care provider might come and visit you in the hospital or at least be in contact with your team,” Dr. Mahajan said in an interview. “That may not happen if you’re going to be seen at five different hospitals in 7 years.”
Encouraging the concept of “medical home” for SCD may be help ease transition from pediatric to adult care, thereby reducing fragmentation of care for young adults, according to Julie A. Panepinto, MD, professor of pediatric hematology and the director of the center for clinical effectiveness research at the Children’s Research Institute, Medical College of Wisconsin, Milwaukee.
“That 18- to 30-year-old age group historically and repeatedly over time is shown to be the age that relies on the emergency department and that has a higher mortality as they transition,” Dr. Panepinto said in an interview. “So ideally, you would have a pediatric program that’s comprehensive and that can transition an adult patient to a very similar setting with knowledgeable providers in SCD across the spectrum, from the emergency department to the hospital to the outpatient clinic.”
Dr. Mahajan reported no disclosures related to her group’s study. Coauthors provided disclosures related to Pfizer and Janssen.
SOURCE: Shatola A et al. ASH 2019. Abstract 4667.
ORLANDO – While over time, results of a retrospective study suggest.
Nearly 60% of children between aged10-17 years were seen at just one facility over the course of 7 years in the analysis, which was based on analysis of data for nearly 7,000 patients seen in California during 1991-2016.
That contrasted sharply with young adults, aged 18-25 years, only about 20% of whom were admitted to one facility, said senior study author Anjlee Mahajan, MD, of the University of California, Davis, adding that another 20% were seen at five or more centers over a 7-year follow-up period.
Fragmentation of care didn’t increase the risk of death in this study, as investigators hypothesized it might. However, the outcomes and the quality of care among young adults with SCD who received inpatient care at multiple facilities nevertheless was likely to be affected, Dr. Mahajan said at the annual meeting of the American Society of Hematology.
“Imagine what that would be like to have a chronic, debilitating illness and to have to go to multiple different hospitals, during this vulnerable time period in your life, and being seen by different care providers who may not know you and may not have all of your records as well,” she said in a press conference at the meeting.
Providers and the health care system need to work harder to ensure young adults receive comprehensive and coordinated care, especially at a time when therapeutic advances are improving the treatment of this disease, according to the investigator.
“When you’re seen at one center, you can have a specific pain plan, and maybe when you are going into the emergency room and being admitted, your sickle cell care provider might come and visit you in the hospital or at least be in contact with your team,” Dr. Mahajan said in an interview. “That may not happen if you’re going to be seen at five different hospitals in 7 years.”
Encouraging the concept of “medical home” for SCD may be help ease transition from pediatric to adult care, thereby reducing fragmentation of care for young adults, according to Julie A. Panepinto, MD, professor of pediatric hematology and the director of the center for clinical effectiveness research at the Children’s Research Institute, Medical College of Wisconsin, Milwaukee.
“That 18- to 30-year-old age group historically and repeatedly over time is shown to be the age that relies on the emergency department and that has a higher mortality as they transition,” Dr. Panepinto said in an interview. “So ideally, you would have a pediatric program that’s comprehensive and that can transition an adult patient to a very similar setting with knowledgeable providers in SCD across the spectrum, from the emergency department to the hospital to the outpatient clinic.”
Dr. Mahajan reported no disclosures related to her group’s study. Coauthors provided disclosures related to Pfizer and Janssen.
SOURCE: Shatola A et al. ASH 2019. Abstract 4667.
ORLANDO – While over time, results of a retrospective study suggest.
Nearly 60% of children between aged10-17 years were seen at just one facility over the course of 7 years in the analysis, which was based on analysis of data for nearly 7,000 patients seen in California during 1991-2016.
That contrasted sharply with young adults, aged 18-25 years, only about 20% of whom were admitted to one facility, said senior study author Anjlee Mahajan, MD, of the University of California, Davis, adding that another 20% were seen at five or more centers over a 7-year follow-up period.
Fragmentation of care didn’t increase the risk of death in this study, as investigators hypothesized it might. However, the outcomes and the quality of care among young adults with SCD who received inpatient care at multiple facilities nevertheless was likely to be affected, Dr. Mahajan said at the annual meeting of the American Society of Hematology.
“Imagine what that would be like to have a chronic, debilitating illness and to have to go to multiple different hospitals, during this vulnerable time period in your life, and being seen by different care providers who may not know you and may not have all of your records as well,” she said in a press conference at the meeting.
Providers and the health care system need to work harder to ensure young adults receive comprehensive and coordinated care, especially at a time when therapeutic advances are improving the treatment of this disease, according to the investigator.
“When you’re seen at one center, you can have a specific pain plan, and maybe when you are going into the emergency room and being admitted, your sickle cell care provider might come and visit you in the hospital or at least be in contact with your team,” Dr. Mahajan said in an interview. “That may not happen if you’re going to be seen at five different hospitals in 7 years.”
Encouraging the concept of “medical home” for SCD may be help ease transition from pediatric to adult care, thereby reducing fragmentation of care for young adults, according to Julie A. Panepinto, MD, professor of pediatric hematology and the director of the center for clinical effectiveness research at the Children’s Research Institute, Medical College of Wisconsin, Milwaukee.
“That 18- to 30-year-old age group historically and repeatedly over time is shown to be the age that relies on the emergency department and that has a higher mortality as they transition,” Dr. Panepinto said in an interview. “So ideally, you would have a pediatric program that’s comprehensive and that can transition an adult patient to a very similar setting with knowledgeable providers in SCD across the spectrum, from the emergency department to the hospital to the outpatient clinic.”
Dr. Mahajan reported no disclosures related to her group’s study. Coauthors provided disclosures related to Pfizer and Janssen.
SOURCE: Shatola A et al. ASH 2019. Abstract 4667.
REPORTING FROM ASH 2019
Care coordination, equity can eliminate disparities for nonwhite patients with DLBCL
ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.
Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.
He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.
“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.
Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.
The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.
The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.
The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.
They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.
Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.
Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.
Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.
The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.
In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.
In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.
For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.
Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”
The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.
SOURCE: Hu B et al. ASH 2019. Abstract 425.
ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.
Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.
He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.
“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.
Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.
The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.
The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.
The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.
They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.
Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.
Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.
Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.
The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.
In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.
In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.
For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.
Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”
The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.
SOURCE: Hu B et al. ASH 2019. Abstract 425.
ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.
Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.
He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.
“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.
Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.
The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.
The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.
The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.
They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.
Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.
Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.
Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.
The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.
In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.
In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.
For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.
Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”
The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.
SOURCE: Hu B et al. ASH 2019. Abstract 425.
REPORTING FROM ASH 2019
Aspirin plus a DOAC may do more harm than good in some
ORLANDO – in a large registry-based cohort.
The study, which involved a cohort of 2,045 patients who were followed at 6 anticoagulation clinics in Michigan during January 2009–June 2019, also found no apparent improvement in thrombosis incidence with the addition of aspirin, Jordan K. Schaefer, MD, reported during a press briefing at the annual meeting of the American Society of Hematology.
Of the cohort patients, 639 adults who received a DOAC plus aspirin after VTE or for NVAF without a clear indication were compared with 639 propensity-matched controls. The bleeding event rate per 100 patient years was 39.50 vs. 32.32 at an average of 15.2 months of follow-up in the combination therapy and DOAC monotherapy groups, respectively, said Dr. Schaefer of the division of hematology/oncology, department of internal medicine, University of Michigan, Ann Arbor.
“This result was statistically significant for clinically relevant non-major bleeding, with an 18.7 rate per 100 patient years, compared with 13.5 for DOAC monotherapy,” (P = .02), he said. “We also saw a significant increase in non-major bleeding with combination therapy, compared with direct oral anticoagulant monotherapy” (rate, 32.82 vs. 25.88; P =.04).
No significant difference was seen overall (P =.07) or for other specific types of bleeding, he noted.
The observed rates of thrombosis in the groups, respectively, were 2.35 and 2.23 per 100 patient years (P =.95), he said, noting that patients on combination therapy also had more emergency department visits and hospitalizations, but those differences were not statistically significant.
“Direct-acting oral anticoagulants, which include apixaban, dabigatran, edoxaban, and rivaroxaban, are increasingly used in clinical practice for indications that include the prevention of strokes for patients with nonvalvular atrial fibrillation, and the treatment and secondary prevention of venous thromboembolic disease,” Dr. Schaefer said.
Aspirin is commonly used in clinical practice for various indications, including primary prevention of heart attacks, strokes, and colorectal cancer, as well as for thromboprophylaxis in patients with certain blood disorders or with certain cardiac devices, he added.
“Aspirin is used for the secondary prevention of thrombosis for patients with known coronary artery disease, peripheral artery disease, or carotid artery disease,” he said. “And while adding aspirin to a DOAC is often appropriate after acute coronary syndromes or percutaneous coronary intervention, many patients receive the combination therapy without a clear indication, he said, noting that increasing evidence in recent years, largely from patients treated with warfarin and aspirin, suggest that the approach may do more harm than good for certain patients.
Specifically, there’s a question of whether aspirin is increasing the rates of bleeding without protecting patients from adverse thrombotic outcomes.
“This has specifically been a concern for patients who are on full-dose anticoagulation,” he said.
In the current study, patient demographics, comorbidities, and concurrent medications were well balanced in the treatment and control groups after propensity score matching, he said, noting that patients with a history of heart valve replacement, recent MI, or less than 3 months of follow-up were excluded.
“These findings need to be confirmed in larger studies, but until such data [are] available, clinicians and patients should continue to balance the relative risks and benefits of adding aspirin to their direct oral anticoagulant therapy,” Dr. Schaefer said. “Further research needs to evaluate key subgroups to see if any particular population may benefit from combination therapy compared to DOAC therapy alone.”
Dr. Schaefer reported having no disclosures.
SOURCE: Schaeffer J et al. ASH 2019. Abstract 787.
ORLANDO – in a large registry-based cohort.
The study, which involved a cohort of 2,045 patients who were followed at 6 anticoagulation clinics in Michigan during January 2009–June 2019, also found no apparent improvement in thrombosis incidence with the addition of aspirin, Jordan K. Schaefer, MD, reported during a press briefing at the annual meeting of the American Society of Hematology.
Of the cohort patients, 639 adults who received a DOAC plus aspirin after VTE or for NVAF without a clear indication were compared with 639 propensity-matched controls. The bleeding event rate per 100 patient years was 39.50 vs. 32.32 at an average of 15.2 months of follow-up in the combination therapy and DOAC monotherapy groups, respectively, said Dr. Schaefer of the division of hematology/oncology, department of internal medicine, University of Michigan, Ann Arbor.
“This result was statistically significant for clinically relevant non-major bleeding, with an 18.7 rate per 100 patient years, compared with 13.5 for DOAC monotherapy,” (P = .02), he said. “We also saw a significant increase in non-major bleeding with combination therapy, compared with direct oral anticoagulant monotherapy” (rate, 32.82 vs. 25.88; P =.04).
No significant difference was seen overall (P =.07) or for other specific types of bleeding, he noted.
The observed rates of thrombosis in the groups, respectively, were 2.35 and 2.23 per 100 patient years (P =.95), he said, noting that patients on combination therapy also had more emergency department visits and hospitalizations, but those differences were not statistically significant.
“Direct-acting oral anticoagulants, which include apixaban, dabigatran, edoxaban, and rivaroxaban, are increasingly used in clinical practice for indications that include the prevention of strokes for patients with nonvalvular atrial fibrillation, and the treatment and secondary prevention of venous thromboembolic disease,” Dr. Schaefer said.
Aspirin is commonly used in clinical practice for various indications, including primary prevention of heart attacks, strokes, and colorectal cancer, as well as for thromboprophylaxis in patients with certain blood disorders or with certain cardiac devices, he added.
“Aspirin is used for the secondary prevention of thrombosis for patients with known coronary artery disease, peripheral artery disease, or carotid artery disease,” he said. “And while adding aspirin to a DOAC is often appropriate after acute coronary syndromes or percutaneous coronary intervention, many patients receive the combination therapy without a clear indication, he said, noting that increasing evidence in recent years, largely from patients treated with warfarin and aspirin, suggest that the approach may do more harm than good for certain patients.
Specifically, there’s a question of whether aspirin is increasing the rates of bleeding without protecting patients from adverse thrombotic outcomes.
“This has specifically been a concern for patients who are on full-dose anticoagulation,” he said.
In the current study, patient demographics, comorbidities, and concurrent medications were well balanced in the treatment and control groups after propensity score matching, he said, noting that patients with a history of heart valve replacement, recent MI, or less than 3 months of follow-up were excluded.
“These findings need to be confirmed in larger studies, but until such data [are] available, clinicians and patients should continue to balance the relative risks and benefits of adding aspirin to their direct oral anticoagulant therapy,” Dr. Schaefer said. “Further research needs to evaluate key subgroups to see if any particular population may benefit from combination therapy compared to DOAC therapy alone.”
Dr. Schaefer reported having no disclosures.
SOURCE: Schaeffer J et al. ASH 2019. Abstract 787.
ORLANDO – in a large registry-based cohort.
The study, which involved a cohort of 2,045 patients who were followed at 6 anticoagulation clinics in Michigan during January 2009–June 2019, also found no apparent improvement in thrombosis incidence with the addition of aspirin, Jordan K. Schaefer, MD, reported during a press briefing at the annual meeting of the American Society of Hematology.
Of the cohort patients, 639 adults who received a DOAC plus aspirin after VTE or for NVAF without a clear indication were compared with 639 propensity-matched controls. The bleeding event rate per 100 patient years was 39.50 vs. 32.32 at an average of 15.2 months of follow-up in the combination therapy and DOAC monotherapy groups, respectively, said Dr. Schaefer of the division of hematology/oncology, department of internal medicine, University of Michigan, Ann Arbor.
“This result was statistically significant for clinically relevant non-major bleeding, with an 18.7 rate per 100 patient years, compared with 13.5 for DOAC monotherapy,” (P = .02), he said. “We also saw a significant increase in non-major bleeding with combination therapy, compared with direct oral anticoagulant monotherapy” (rate, 32.82 vs. 25.88; P =.04).
No significant difference was seen overall (P =.07) or for other specific types of bleeding, he noted.
The observed rates of thrombosis in the groups, respectively, were 2.35 and 2.23 per 100 patient years (P =.95), he said, noting that patients on combination therapy also had more emergency department visits and hospitalizations, but those differences were not statistically significant.
“Direct-acting oral anticoagulants, which include apixaban, dabigatran, edoxaban, and rivaroxaban, are increasingly used in clinical practice for indications that include the prevention of strokes for patients with nonvalvular atrial fibrillation, and the treatment and secondary prevention of venous thromboembolic disease,” Dr. Schaefer said.
Aspirin is commonly used in clinical practice for various indications, including primary prevention of heart attacks, strokes, and colorectal cancer, as well as for thromboprophylaxis in patients with certain blood disorders or with certain cardiac devices, he added.
“Aspirin is used for the secondary prevention of thrombosis for patients with known coronary artery disease, peripheral artery disease, or carotid artery disease,” he said. “And while adding aspirin to a DOAC is often appropriate after acute coronary syndromes or percutaneous coronary intervention, many patients receive the combination therapy without a clear indication, he said, noting that increasing evidence in recent years, largely from patients treated with warfarin and aspirin, suggest that the approach may do more harm than good for certain patients.
Specifically, there’s a question of whether aspirin is increasing the rates of bleeding without protecting patients from adverse thrombotic outcomes.
“This has specifically been a concern for patients who are on full-dose anticoagulation,” he said.
In the current study, patient demographics, comorbidities, and concurrent medications were well balanced in the treatment and control groups after propensity score matching, he said, noting that patients with a history of heart valve replacement, recent MI, or less than 3 months of follow-up were excluded.
“These findings need to be confirmed in larger studies, but until such data [are] available, clinicians and patients should continue to balance the relative risks and benefits of adding aspirin to their direct oral anticoagulant therapy,” Dr. Schaefer said. “Further research needs to evaluate key subgroups to see if any particular population may benefit from combination therapy compared to DOAC therapy alone.”
Dr. Schaefer reported having no disclosures.
SOURCE: Schaeffer J et al. ASH 2019. Abstract 787.
REPORTING FROM ASH 2019
Kidney function in African American AML patients not linked to reduced survival compared with whites
ORLANDO – While African Americans with acute myeloid leukemia were more likely to have evidence of abnormal kidney function, the excess of this comorbidity didn’t affect overall survival, compared with whites, according to a study of more than 1,000 patients.
A total of 63% of African Americans with acute myeloid leukemia (AML) presented with a renal function abnormality that could have excluded them from a clinical trial, compared with 56% in the overall cohort; however, analysis of outcomes data suggested that renal function abnormalities were not associated with decreased survival in African Americans versus whites, said Abby Statler, PhD, MPH, of the Cleveland Clinic.
The findings may have implications for the design of clinical trials that might exclude patients on the basis of comorbidities that don’t actually affect survival, according to Dr. Statler.
“If we’re able to liberalize renal function eligibility criteria ... this may reduce racial disparities in clinical trial enrollment, which might be a major step in improving the diversity of cancer patient populations,” Dr. Statler said in a press conference at the annual meeting of the American Society of Hematology.
Overly restrictive criteria could be a significant barrier to clinical trial enrollment among minority patient populations, according to Dr. Statler.
Eligibility criteria are generally biased toward “fit” patient populations, which means they may discriminate against less-fit groups, such as African Americans who, compared with whites, have higher rates of comorbidities and report poorer overall health, according to Dr. Statler.
Laura Michaelis, MD, who chaired the press conference, said these findings suggest current clinical trial designs may be “too restrictive.”
“Once it’s published and validated, [these] data should definitely make us think twice about when you limit a patient’s enrollment in a trial,” Dr. Michaelis said in an interview.
Restrictive eligibility criteria may not only limit access to minority populations, but also may slow clinical trial accrual and completion, and make it harder to generalize clinical trial findings to the overall population, said Dr. Michaelis, associate professor of medicine in the division of hematology and oncology, Medical College of Wisconsin, Milwaukee.
The study by Dr. Statler and colleagues included 1,040 AML patients who received chemotherapy at Cleveland Clinic between 2003 and 2019. About 10% of the patients in the analysis were African American and 90% were white.
Median overall survival was not significantly different by race, at 13.7 months for African Americans and 14.9 months for whites (P = 0.89), according to results published in the study abstract.
Mild creatinine elevation did not appear to affect survival in this study, according to the investigator. Survival was not significantly different between patients with normal creatinine and those with creatinine up to 1.5 times the upper limit of normal. However, higher levels of creatinine were significantly associated with worse survival, Dr. Statler said.
Further analyses showed that these survival findings by creatinine level held up specifically in the African American subgroup as well, Dr. Statler said in the press conference.
Dr. Statler provided no disclosures related to the presentation. Study coauthors described disclosures related to Amgen, SimulStat, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, Celgene Corporation, Abbvie, and Incyte, among others.
SOURCE: Statler A et al. ASH 2019, Abstract 381.
ORLANDO – While African Americans with acute myeloid leukemia were more likely to have evidence of abnormal kidney function, the excess of this comorbidity didn’t affect overall survival, compared with whites, according to a study of more than 1,000 patients.
A total of 63% of African Americans with acute myeloid leukemia (AML) presented with a renal function abnormality that could have excluded them from a clinical trial, compared with 56% in the overall cohort; however, analysis of outcomes data suggested that renal function abnormalities were not associated with decreased survival in African Americans versus whites, said Abby Statler, PhD, MPH, of the Cleveland Clinic.
The findings may have implications for the design of clinical trials that might exclude patients on the basis of comorbidities that don’t actually affect survival, according to Dr. Statler.
“If we’re able to liberalize renal function eligibility criteria ... this may reduce racial disparities in clinical trial enrollment, which might be a major step in improving the diversity of cancer patient populations,” Dr. Statler said in a press conference at the annual meeting of the American Society of Hematology.
Overly restrictive criteria could be a significant barrier to clinical trial enrollment among minority patient populations, according to Dr. Statler.
Eligibility criteria are generally biased toward “fit” patient populations, which means they may discriminate against less-fit groups, such as African Americans who, compared with whites, have higher rates of comorbidities and report poorer overall health, according to Dr. Statler.
Laura Michaelis, MD, who chaired the press conference, said these findings suggest current clinical trial designs may be “too restrictive.”
“Once it’s published and validated, [these] data should definitely make us think twice about when you limit a patient’s enrollment in a trial,” Dr. Michaelis said in an interview.
Restrictive eligibility criteria may not only limit access to minority populations, but also may slow clinical trial accrual and completion, and make it harder to generalize clinical trial findings to the overall population, said Dr. Michaelis, associate professor of medicine in the division of hematology and oncology, Medical College of Wisconsin, Milwaukee.
The study by Dr. Statler and colleagues included 1,040 AML patients who received chemotherapy at Cleveland Clinic between 2003 and 2019. About 10% of the patients in the analysis were African American and 90% were white.
Median overall survival was not significantly different by race, at 13.7 months for African Americans and 14.9 months for whites (P = 0.89), according to results published in the study abstract.
Mild creatinine elevation did not appear to affect survival in this study, according to the investigator. Survival was not significantly different between patients with normal creatinine and those with creatinine up to 1.5 times the upper limit of normal. However, higher levels of creatinine were significantly associated with worse survival, Dr. Statler said.
Further analyses showed that these survival findings by creatinine level held up specifically in the African American subgroup as well, Dr. Statler said in the press conference.
Dr. Statler provided no disclosures related to the presentation. Study coauthors described disclosures related to Amgen, SimulStat, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, Celgene Corporation, Abbvie, and Incyte, among others.
SOURCE: Statler A et al. ASH 2019, Abstract 381.
ORLANDO – While African Americans with acute myeloid leukemia were more likely to have evidence of abnormal kidney function, the excess of this comorbidity didn’t affect overall survival, compared with whites, according to a study of more than 1,000 patients.
A total of 63% of African Americans with acute myeloid leukemia (AML) presented with a renal function abnormality that could have excluded them from a clinical trial, compared with 56% in the overall cohort; however, analysis of outcomes data suggested that renal function abnormalities were not associated with decreased survival in African Americans versus whites, said Abby Statler, PhD, MPH, of the Cleveland Clinic.
The findings may have implications for the design of clinical trials that might exclude patients on the basis of comorbidities that don’t actually affect survival, according to Dr. Statler.
“If we’re able to liberalize renal function eligibility criteria ... this may reduce racial disparities in clinical trial enrollment, which might be a major step in improving the diversity of cancer patient populations,” Dr. Statler said in a press conference at the annual meeting of the American Society of Hematology.
Overly restrictive criteria could be a significant barrier to clinical trial enrollment among minority patient populations, according to Dr. Statler.
Eligibility criteria are generally biased toward “fit” patient populations, which means they may discriminate against less-fit groups, such as African Americans who, compared with whites, have higher rates of comorbidities and report poorer overall health, according to Dr. Statler.
Laura Michaelis, MD, who chaired the press conference, said these findings suggest current clinical trial designs may be “too restrictive.”
“Once it’s published and validated, [these] data should definitely make us think twice about when you limit a patient’s enrollment in a trial,” Dr. Michaelis said in an interview.
Restrictive eligibility criteria may not only limit access to minority populations, but also may slow clinical trial accrual and completion, and make it harder to generalize clinical trial findings to the overall population, said Dr. Michaelis, associate professor of medicine in the division of hematology and oncology, Medical College of Wisconsin, Milwaukee.
The study by Dr. Statler and colleagues included 1,040 AML patients who received chemotherapy at Cleveland Clinic between 2003 and 2019. About 10% of the patients in the analysis were African American and 90% were white.
Median overall survival was not significantly different by race, at 13.7 months for African Americans and 14.9 months for whites (P = 0.89), according to results published in the study abstract.
Mild creatinine elevation did not appear to affect survival in this study, according to the investigator. Survival was not significantly different between patients with normal creatinine and those with creatinine up to 1.5 times the upper limit of normal. However, higher levels of creatinine were significantly associated with worse survival, Dr. Statler said.
Further analyses showed that these survival findings by creatinine level held up specifically in the African American subgroup as well, Dr. Statler said in the press conference.
Dr. Statler provided no disclosures related to the presentation. Study coauthors described disclosures related to Amgen, SimulStat, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, Celgene Corporation, Abbvie, and Incyte, among others.
SOURCE: Statler A et al. ASH 2019, Abstract 381.
REPORTING FROM ASH 2019