HSCT with total body irradiation vs. chemotherapy-based conditioning improves ALL outcomes
Click Here to Manage Email Alerts
Allogeneic hematopoietic stem cell transplants with total body irradiation and etoposide vs. chemotherapy-based conditioning regimens conferred superior OS for children with acute lymphoblastic leukemia, randomized study results showed.
The results, presented during the virtual European Hematology Association Annual Congress, also demonstrated that bulsufan- or treosulfan-based chemotherapy conditioning regimens that included fludarabine and thiotepa are valuable alternative options for patients ineligible for total body irradiation because of comorbidities or age.
Total body irradiation is the most commonly used myeloablative strategy for patients with ALL who undergo HSCT. However, it can be accompanied by significant acute and late toxicities.
Christina Peters, MD, PhD, professor of pediatrics at the department of stem cell transplantation of St. Anna Children's Hospital in Vienna, Austria, and colleagues sought to determine whether chemotherapy-based conditioning could be used instead of total body irradiation for these patients. They randomly assigned 413 children aged 4 years and older undergoing HSCT with a matched-sibling or matched-unrelated donor to a chemotherapy-based conditioning regimen (n = 192) or total body irradiation with etoposide (n = 202). Nine randomly assigned children did not undergo HSCT.
Chemotherapy regimens consisted of fludarabine, thiotepa and busulfan (n = 99) or fludarabine, thiotepa and treosulfan (n = 93).
OS served as the study’s primary endpoint. Researchers aimed to demonstrate noninferiority of the chemotherapy conditioning regimen with one-sided 95% CIs and a non-inferiority margin of 8%.
Researchers transplanted patients in first complete remission (54%), second complete remission (40%) and third complete remission (4%).
Among patients in second complete remission, 13% experienced very early relapse, 34% experienced early relapse and 53% experienced late relapse.
Bone marrow served as a stem cell source for 82% of patients. Peripheral blood stem cells were the source in 12% of transplants, whereas cord blood was the source in 4%.
With median follow-up of 2.1 years, results showed 2-year OS of 75% ± 4% for the chemotherapy conditioning group and 91% ± 2% for the total body irradiation group (P < .001).
Results of a per-protocol analysis showed OS of 77% ± 5% after each chemotherapy regimen and 91% ± 2% after total body irradiation (P = .003).
Researchers stopped randomization mid-trial due to significantly inferior outcomes with the chemotherapy-based conditioning.
Results also showed 2-year EFS of 85% ± 3% for the total body irradiation group, 64% ± 6% for the busulfan chemotherapy group and 58% ± 6% for the treosulfan group (P = .003), and 2-year cumulative incidence of relapse of 12% ± 4% with irradiation, 3% ± 5% with busulfan chemotherapy and 31% ± 5% with treosulfan chemotherapy (P = .004).
Researchers observed no significant difference among the groups in 2-year treatment-related mortality or incidence of acute and chronic graft-versus-host disease.
“Prospective monitoring of late complications, endocrine functions and incidence of secondary malignancies will contribute to better define the advantages and limitations of the three conditioning approaches,” the researchers wrote in the abstract.
Collapse
Peters C, et al. Abstract S102. Presented at: European Hematology Association Annual Congress (virtual meeting); June 11-21, 2020.
Click Here to Manage Email Alerts