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Busulfan–melphalan combination prepares patients with AML for transplantation
Autologous hematopoietic stem cell transplantation outcomes appeared improved in patients with acute myelogenous leukemia in first complete remission who received a preparative regimen with busulfan and melphalan compared with those who received busulfan and cyclophosphamide, according to a retrospective, multicenter analysis published in Cancer.
“Our analysis of BUMEL (busulfan and melphalan) versus BUCY (busulfan and cyclophosphamide) in patients who underwent autograft in molecular remission suggests that, even in this highly selected group of patients with no detectable minimal residual disease who currently are believed to benefit from autologous HSCT, BUMEL also may result in a better outcome than BUCY,” Norbert-Claude Gorin, MD, PhD, professor in the department of hematology and cellular therapy at St. Antoine Hospital in Paris, and colleagues wrote.
The most common pretreatment for autologous HSCT has been 16 mg/kg busulfan with 120 mg/kg cyclophosphamide. However, two retrospective studies from the Italian Group for Blood and Marrow Transplantation and the European Society for Blood and Marrow Transplantation suggested that BUMEL may be associated with improved outcomes.
Gorin and colleagues used the European Society’s registry to analyze data from 853 patients, of whom 596 received BUCY (58% men; median age, 49.6 years) and 257 received BUMEL (52% men; median age, 50.8 years) from 2005 to 2013.
Patients received busulfan either orally (16 mg/kg over 4 days) or intravenously (12.8 mg/kg over 4 days). Patients received busulfan either 60 mg/kg cyclophosphamide for 2 days, or 140 mg/m2 high-dose melphalan.
The median follow-up for surviving patients was 44.2 months (range, 1.08-127.8 months) for patients treated with BUCY and 50.33 months (range, 1.57-124.66 months) for patients treated with BUMEL.
The proportion of patients with good-risk AML was lower in those who received BUMEL than BUCY (14% vs. 20%; P = .02).
More patients who received BUMEL underwent autograft in molecular remission (89% vs. 78%, P = 0.2).
Overall, 3 years after transplantation, the relapse incidence was 48.7%, the leukemia-free survival rate was 47.7%, the OS rate was 66.2%, and the nonrelapse mortality rate was 3.6%.
Researchers reported that, at 3 years, patients who underwent an autograft after receiving BUMEL had a lower relapse incidence (39.5% vs. 52.2%; HR = 0.65; 95% CI, 0.49-0.87), a better leukemia-free survival rate (55.4% vs. 44.6%; HR = 0.69; 95% CI, 0.53-0.89) and a better OS rate (73.8% vs. 63%; HR = 0.62; 95% CI, 0.47-0.82).
There was no significant difference in the nonrelapse mortality rate.
Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, those receiving BUMEL experienced lower relapse incidence (30% vs. 51%; P = .01) and a higher leukemia-free survival rate (66% vs. 47%; P = .03).
Gorin and colleagues acknowledged there may be differences in patient, disease and transplantation characteristics between those who received BUMEL and those who received BUCY, which are inherent limitations in a retrospective analysis.
“Obviously, these findings would support the launch of a randomized trial comparing BUMEL versus BUCY for autologous HSCT in patients with AML,” Gorin and colleagues wrote. “However, such a randomized study is unlikely to be done, and we believe that the results from this analysis, although they are retrospective, in the absence of available prospective data, make the BUMEL conditioning regimen before autologous HSCT a first choice.”– by Chuck Gormley
Disclosure: One researcher reports grants and personal fees from Pierre Fabre Medicament during the study.