High-Dose Melphalan Followed by Busulfan and Fludarabine Conditioning Prior to Allogeneic Stem Cell Transplantation in Elderly Patients with Active Acute Myeloid Leukemia—A Retrospective Single-Center Study

In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term survival in most cases can only be achieved with allogeneic hematopoietic stem cell transplantation. The introduction of sequential conditioning regimens has contributed to the steadily improving prognosis of r/r AML patients. As most studies mainly included younger patients, feasibility of sequential conditioning in elderly or comorbid patients remains subject of debate. We retrospectively investigated outcomes of 103 patients aged ≥55 years with active r/r AML receiving sequential melphalan-based conditioning followed by fludarabine and busulfan at our center from 2014 to 2022. The median (range) age in our cohort was 67 (55 to 76) years. Thirty-one percent of the patients had hematopoietic cell transplantation comorbidity index scores >3 points. Overall survival (OS) and relapse-free survival estimates at 3 years were 44% (95% confidence interval [CI], 35% to 55%) and 40% (95% CI, 31% to 51%), respectively. Cumulative incidences of relapse and nonrelapse mortality (NRM) at 3 years were 28% (95% CI, 19% to 37%) and 32% (95% CI, 23% to 41%), respectively. Transplantation from a mismatched donor was identified as major risk factor for OS (adjusted hazard ratio [HR_adj] 3.03; 95% CI, 1.72 to 5.35; P < .001) and NRM (HR_adj 2.86; 95% CI, 1.38 to 5.93; P = .005). A high leukemic burden before conditioning (20% to 49% versus 5% to 19% bone marrow blasts, HR_adj 3.00; 95% CI, 1.10 to 8.18; P = .032) was associated with an increased relapse risk. In summary, our data suggest that sequential conditioning with melphalan followed by busulfan and fludarabine is effective and tolerable in elderly patients with active AML, allowing for 3-year OS of >40%. At the same time, our data highlight the need to refine treatment strategies for elderly patients with active AML who receive transplants from <10/10 matched donors, or patients with high leukemic burden.