Etoposide plus cytarabine versus cyclophosphamide or melphalan in busulfan-based preparative regimens for autologous stem cell transplantation in adults with acute myeloid leukemia in first complete remission: a study from the Acute Leukemia Working Party of the EBMT.

We retrospectively compared the impact of the conditioning regimen in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) that received high-dose myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) from 2010 to 2021 with either high-dose cytarabine, etoposide and busulfan (BEA), busulfan with cyclophosphamide (BUCY) or busulfan and high-dose melphalan (BUMEL) registered in the EBMT database. Overall 1560 patients underwent ASCT, of which 156, 1143 and 261 received BEA, BUCY and BUMEL, respectively. Compared to BUCY and BUMEL, BEA patients were younger (p < 0.001) and less frequently had NPM1 mutations (p = 0.03). Transplant outcomes at 5 years with BEA, BUCY and BUMEL were: cumulative incidence of relapse 41.8%, 46.6% and 51.6%; non-relapse mortality (NRM) 1.5%, 5.2% and 7.3%; probability of leukemia-free survival (LFS) 56.7%, 48.2% and 41.1%; and overall survival (OS) 71.3%, 62.3% and 56%, respectively. In multivariable analysis the BEA regimen showed significant improvement in OS compared to BUCY (hazard ratio [HR] 0.65; 95% CI, 0.42-0.83; p = 0.048) and BUMEL (HR 0.59; 95% CI, 0.37-0.94; p = 0.029). In conclusion, high-dose myeloablative combination chemotherapy with BEA offered improved outcomes compared to classical BUCY or BUMEL in patients with AML in CR1 undergoing ASCT.