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

Abstract Introduction High-dose myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) is a valid treatment option for patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, information on specific conditioning regimens is scarce. The ALWP showed improved outcomes with busulfan and high-dose melphalan (BUMEL) conditioning compared to busulfan with cyclophosphamide (BUCY) in high-risk patients. The combination of more AML directed drugs using high-dose cytarabine, etoposide and busulfan (BEA) has been the recommended regimen in subsequent PETHEMA studies. Methods In order to analyse the impact of the conditioning regimen we retrospectively compared the outcome of adult patients with AML in CR1 that received an ASCT from 2010 to 2021 with either BEA, BUCY or BUMEL registered in the EBMT database. Results Overall 1560 patients underwent ASCT at a median age of 52 years (range, 18–75). Eight hundred and forty-three (54%) were male. Two hundred and sixty-seven (23%), 815 (70%) and 75 (7%) had favorable-, intermediate- and adverse-risk cytogenetics, respectively (data not reported for 403 patients). FLT3-ITD and NPM1 mutations were present in 177 (23%) and 481 (58%) patients, respectively. Regarding conditioning, 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). Favorable cytogenetics and younger age were also associated with improved OS. Conclusions High-dose myeloablative combination chemotherapy with BEA offered improved outcomes compared to classical BUCY or BUMEL in patients with AML in CR1 undergoing ASCT.