Outcomes after HLA-Identical Sibling Allogeneic Peripheral Blood Stem Cell Transplantation Using Reduced Intensity Conditioning Compared to Autologous Peripheral Blood Stem Cell Transplantation for Elderly Patients with De Novo Acute Myeloid Leukemia.

Results of allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients are associated to high TRM mainly due to toxic effects of myeloablative preparative regimen allogeneic and GVHD. Therefore, chemotherapy or autologous (auto) HSCT are often treatment alternatives. Recently, allogeneic peripheral blood SCT (PBSCT) with reduced-intensity conditioning (RIC) has emerged as an alternative to decrease TRM and to add a GVL effect. We have conducted a registry-based retrospective risk-adjusted comparative analysis of outcomes of 204 RIC-PBSCT to those of 954 auto-PBSCT in adult patients aged 50 years or older with de novo AML. Transplants were performed from 1997 until 2003 and reported to the EBMT. Median age was similar in both groups (58 y in RIC and 57y auto PBST), however RIC patients were transplanted more recently, had more advanced disease at time of transplant and poorer cytogenetics compared to the auto-PSCT group (p<0.05). The majority of conditioning regimens used in the RIC group was fludarabine-based associated to low dose TBI or Busulfan (<8mg/kg). Median follow-up was 13 months in both groups. Median time to engraftment was 16 days in the RIC group and 12 days in the auto group (p <0.0001). Unadjusted one-year probability of TRM was 15 ±3% in RIC and 8±1% in auto (p=0.002) and one-year probability of relapse were 34 ±3% in the RIC group versus 40 ±2% in the auto group (p = 0.31). However after adjustment, multivariate analysis showed a lower risk for relapse (RR 0.75, p = 0.04) but a trend for a higher TRM (RR 1.57, p = 0.07) for RIC patients. Major causes of non leukemic death in the RIC group were infections and graft-versus-host disease; and in the auto group, infections. Unadjusted one-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were not statistically different in both groups: LFS of 50±4% in the RIC group versus 52±2% in the auto group (p = 0.31), and OS of 62±4% versus 66±2% (p = 0.23), respectively. In a multivariate analysis, OS and LFS were not statistically different for both groups. In the subgroup analysis, unadjusted one-year probability of LFS was 62±8% for patients in 2^nd complete remission receiving RIC transplants compared to 43±6% (p=0.02). Conclusion: Allogeneic HLA identical RIC PBSCT is an effective treatment option for older patients with AML, with acceptable overall survival and decreased relapse incidence compared to autologous PBSCT. These results suggest that RIC PBSCT are feasible in a high risk population and should be evaluated in prospective trials in elderly AML.