First Line Therapy with Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation for Patients with Acute Myeloblastic Leukemia in First Complete Remission.

We investigated the potential benefit of reduced intensity conditioning (RIC) prior to allogeneic stem-cell transplantation (Allo-SCT) in patients with acute myeloblastic leukemia (AML) in first complete remission (CR1). Thirty-six patients (age: 52 (range, 26–60)) with high risk clinical characteristics (n=28; 78%) (Age ≥50 (n=25, 69%); associated severe comorbidity (n=9; 35%)) and/or poor risk leukemic features (n=23; 64%) (poor cytogenetics (n=12, 23%); failure of first induction course (n= 8, 22%); secondary leukemia (n= 6; 17%), High white blood cell counts (n= 5; 14%) or partial remission (n=1, 3%)) were included in this analysis. After CR1, five patients did not receive any consolidation chemotherapy, while 20 were treated with one course of high dose cytarabine (HIDAC). The remaining 11 patients received in addition to HIDAC, a second course of melphalan followed by autologous SCT. All patients received then Allo-SCT prepared with RIC (fludarabine (180 mg/m²), busulfan (8 mg/kg), Thymoglobulin (2.5 to 10 mg/kg)) followed with BMT (n=10 (28%) or PBSCT (n=26 (72%)). Two deaths were attributed to non-relapse causes (cumulative incidence of non-relapse death (NRD): 6% (95% CI: 0–14). In all, 11 patients relapsed (cumulative incidence: 31% (95%CI, 15–46). With a median follow-up of 16 (range, 4–68) months, 26 patients are still alive, of whom 23 in CR1, for an overall survival and leukemia-free survival (LFS) probabilities at 18 months, of 65 % (95%CI, 45–80%) and 63% (95%CI, 46–78%) respectively. In a univariate analysis, the intensity of consolidation chemotherapy (None vs. HIDAC vs. HIDAC + HDM), ATG dose (2.5 mg/kg vs. ≥ 5–10 mg/kg) and the occurrence of clinically significant GVHD (grade 2–4 and/or chronic GVHD vs. none) influenced relapse rate and LFS. In a Cox hazard regression multivariate analysis, the occurrence of GVHD remained the sole independent risk factor for LFS (odds ratio (OR), 8.7, 95% CI, 1.9–39; P=0.005). When restricting the analysis to the 32 patients alive on day 100 and evaluable for chronic GVHD, chronic GVHD remained the only independent risk factor positively influencing LFS (OR, 14, 95% CI, 1.8->50; P=0.013) Finally, if the analysis is focused on patients treated with at least one course of consolidation chemotherapy prior to RIC Allo-SCT, the LFS in patients with high risk leukemic features at 18 month is 75% (95% CI: 50–909%) and 73% (95% CI: 51–87) in patients not eligible for standard myeloablative Allo-SCT comparing favorably with our previous experience and data from the literature. We conclude that RIC Allo-SCT preceded by adequate prior intensive chemotherapy might offer a relatively low NRD while reducing the risk of leukemia relapse even in high risk patients. Therefore, RIC Allo-SCT might represent a valid option for AML patients in CR1 and with high risk clinical characteristics or poor risk leukemic features.