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Pediatric-inspired chemotherapy superior to allogeneic HCT for younger adults with ALL
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Younger adults with Philadelphia chromosome-negative acute lymphoblastic leukemia treated with a pediatric-inspired chemotherapy regimen experienced less treatment-related mortality than those who underwent allogeneic hematopoietic cell transplantation, according to study results.
The pediatric-inspired regimen also appeared associated with longer OS, and researchers reported no significant difference in relapse.
Matthew Seftel, MD, MPH, FRCPC, head of medical oncology and hematology at CancerCare Manitoba, and colleagues reviewed two cohorts of patients with Philadelphia chromosome-negative ALL (Ph-ALL) to determine the effect of pediatric-inspired chemotherapy without hematopoietic cell transplantation (HCT) on durable leukemia-free survival.
The analysis included 422 adults aged 18 to 50 years who underwent HCT at one of 97 centers in the United States and Canada, as well as an age-match cohort of 108 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen.
At 4 years follow-up, researchers reported no significant difference in relapse between the HCT group and chemotherapy group (24% vs. 23%).
However, patients in the HCT group appeared more likely to experience treatment-related mortality (37% vs. 6%; P < .0001) and less likely to achieve 4-year DFS (40% vs. 71%; P < .0001).
Researchers determined receipt of HCT (HR = 6.88; 95% CI, 3.02-15.7), older age (HR = 1.69; 95% CI, 1.16-2.44) and B-cell phenotype (HR = 2.26; 95% CI, 1.3-3.93) all significantly increased the risk for treatment-related death.
The majority (69%) of deaths among patients who received chemotherapy occurred as a result of relapse. In the HCT arm, 28% of deaths occurred as a result of leukemic relapse and 70% were related to HCT-related toxicities.
“Our results indicated a striking advantage in favor of the pediatric chemotherapy approach, [which was] characterized by lower treatment-related mortality, similar relapse risk and superior overall survival,” Seftel told HemOnc Today. “These provocative and clinically relevant results call into question the role of allografting for younger adults with Ph-ALL, and they serve as a strong rationale for randomized controlled trials of HCT vs. non-HCT approaches in adult ALL.” – by Ryan McDonald
For more information:
Matthew Seftel, MD, MPH, FRCPC, can be reached at Department of Medical Oncology and Hematology, ON2047, CancerCare Manitoba, Winnipeg, MB, R3E0V9, Canada; email: mseftel@cancercare.mb.ca.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Edward A. Copelan, MD
Although the cure rate for children with acute lymphoblastic leukemia exceeds 90%, results in adults have not mirrored that level of success. A meta-analysis within the last 3 years reported a 5-year survival of only 49.9% with HLA-identical sibling transplantation in adults with Philadelphia chromosome-negative (PH-) ALL in first complete remission and 42.7% with traditional adult-intensity chemotherapy. The use of pediatric-inspired regimens in adolescents and young adults, and now in adults up to age 50 years, has yielded consistently better survival compared with historical controls treated with traditional adult regimens.
This retrospective comparison essentially juxtaposes results from two different cohorts of patients treated with either pediatric-inspired chemotherapy regimens or transplantation over the same time period and with similar age eligibility. Ironically, the major concern regarding the chemotherapy cohort is one generally ascribed to patients undergoing transplantation: the selection of healthier patients who are more willing and able to travel, and more motivated to receive and comply with the prescribed treatment.
Because we do not know why and how this relatively modest number of patients was selected to receive the chemotherapy regimen — or, for that matter, transplantation — appropriate adjustments cannot be made for potential (unidentified) biases. Further, half of the transplant patients took more than 8 weeks to achieve complete remission while this disqualified patients from the chemotherapy arm, and several patients in the chemotherapy arm underwent transplantation — perhaps for high-risk factors such as specific molecular markers or minimal residual disease — in first complete remission.
These and other factors limit the comparability of these two cohorts and our certainty that pediatric-inspired regimens are better than transplantation in the general population of adults aged 18 to 50 years with Ph-ALL. These data do, however, confirm results achieved in other trials, support the effectiveness of pediatric-inspired therapy in adults with Ph-ALL, and identify the need for randomized controlled trials.
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