Patients with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received fludarabine plus busulfan had significantly lower rates of grade III-IV acute graft-versus-host disease (GVHD) than those who received cyclophosphamide plus busulfan.
Gianluca Cavallaro, MD, of the Department of Oncology-Hematology at Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, and colleagues conducted the research and presented their findings at the 64th American Society of Hematology Annual Meeting and Exposition.
The study included 252 patients with AML who were undergoing allogeneic HSCT, with 213 patients undergoing transplant in their first remission and the remaining patients undergoing transplantation in their second remission. The median patient age was 52 years.
Most patients (54.7%) received transplantation from an unrelated donor, whereas the remaining patients received transplants from a sibling donor. The patients received cyclosporine-A and methotrexate-based GVHD prophylaxis. Thymocyte globulin was used in patients with unrelated donors.
The patients receiving fludarabine plus busulfan had a significantly lower 1-year nonrelapse mortality rate (7.9%) compared with patients receiving cyclophosphamide plus busulfan (17.2%; P=.026). However, there was no difference between treatment groups in the cumulative incidence of relapse, leukemia-free survival rate, or overall survival (OS) rate at 1 and 2 years after transplantation.
However, the rate of grade III-IV acute GVHD was significantly higher in patients receiving cyclophosphamide plus busulfan (10%) than in patients receiving fludarabine plus busulfan (2%).
At a median follow-up of 6 years, the 4-year nonrelapse mortality rate continued to be significantly lower in patients receiving fludarabine plus busulfan (10%) than in patients receiving cyclophosphamide plus busulfan (20%; P=.0388).
However, the 4-year and 10-year cumulative incidences of relapse were similar between treatment groups. The 4-year cumulative incidence of relapse was 36% in patients receiving fludarabine plus busulfan and 33% in those receiving cyclophosphamide plus busulfan. The 10-year cumulative incidence of relapse was 39% in patients receiving fludarabine plus busulfan and 37% in those receiving cyclophosphamide plus busulfan.
The 4-year leukemia-free survival rate was also similar between treatment groups, with a rate of 53% in patients receiving fludarabine plus busulfan and a rate of 47% in those receiving cyclophosphamide plus busulfan. The 4-year OS rate was 56% in both treatment groups. The cumulative incidence of moderate/severe chronic GVHD was 14% in patients receiving fludarabine and busulfan and 19% in those receiving cyclophosphamide plus busulfan.
The 4-year chronic GVHD and leukemia-free survival rate was 35% in patients receiving fludarabine plus busulfan and 24% in patients receiving cyclophosphamide plus busulfan (P=.0602).
“This long-term analysis confirms the benefit in terms of [nonrelapse mortality] associated with the [fludarabine plus busulfan] conditioning, which was not associated to a higher incidence of late leukemia relapse,” Dr. Cavallaro and colleagues concluded. “We found a better trend in [chronic GVHD and leukemia-free survival] in [the fludarabine plus busulfan] arm, most likely due to a lower rate of grade III/IV acute GVHD in the experimental arm.”
Cavallaro G, Grassi A, Pavoni C, et al. Long-term analysis of an open-label, multicentre, randomized phase 3 trial comparing busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic stem-cell transplantation in patients with acute myeloid leukemia. Abstract #3413. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.