BACKGROUND: In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term survival can in most cases only be achieved with allogeneic hematopoietic stem cell transplantation (alloSCT). 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.

OBJECTIVES: 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 2014-2022.

RESULTS: The median (range) age in our cohort was 67 (55-76) years. Thirty-one percent of the patients had HCT-CI scores > 3 points. Overall and relapse-free survival (OS, RFS) estimates at 3 years were 44% (95% confidence interval [CI], 35-55%) and 40% (95% CI, 31-51%), respectively. Cumulative incidences of relapse and non-relapse mortality (NRM) at 3 years were 28% (95% CI, 19-37%) and 32% (95% CI, 23-41%), respectively. Transplantation from a mismatched donor was identified as major risk factor for OS (adjusted hazard ratio [HR_adj] 3.03, 95% CI, 1.72-5.35, P < .001) and NRM (HR_adj 2.86, 95% CI, 1.38-5.93, P = .005). A high leukemic burden before conditioning (20-49% vs. 5-19% bone marrow blasts, HR_adj 3.00, 95% CI, 1.10-8.18, P = .032) was associated with an increased relapse risk.

CONCLUSIONS: 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.