Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Secondary Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndromes (MDS).

Secondary AML and high risk MDS represent a poor risk group of myeloid malignancies. We report here the results of a single center retrospective study of allo-SCT in 28 patients (median age, 42 y.) with secondary AML (n=19; 68%) and MDS (n=9; 22%). Eleven patients (39%) had therapy-related AML (t-AML). FAB categories included: AR/ARS: 3, AREB/AREBt: 6, M0: 1, M1–M2: 9, M4–M5: 5, M6: 3, and one patient could not be classified. Cytogenetics features were: poor risk in 20 patients (71%), normal in 5 patients (19%) and not evaluated in 3 (10%). Allo-SCT was performed as first line therapy in 9 patients (32%) of whom 7 MDS and 2 sAML. The remaining 19 patients (68%), were transplanted after initial induction chemotherapy of whom 17 sAML (89%), and 2 MDS (11%). Median interval between diagnosis and allo-SCT was 3.6 months (range, 1–12). 12 patients (43%) were in complete remission at time of allo-SCT, while 9 patients (32%) were refractory or in progression after treatment, and 7 patients (25%) had stable disease. In 25 cases (89%) donor was a HLA identical sibling, and in 3 cases (11%) a matched unrelated donor. The conditioning regimen was fully myeloablative in 19 patients (68%) including Cy-TBI or BU-Mel or a reduced intensity conditioning (RIC) in 9 patients (32%). Nineteen patients (68%) died after transplantation, of whom 12 patients from non relapse causes (GVHD: 5; infections: 6; multi-organ failure: 1). Seven patients (25%) died from relapse or progression of the disease including 5 patients (18%) with AML and 2 patients (7%) with MDS. The one-year cumulative incidence of transplant related mortality (TRM) was 38%, with TRM being significantly lower in the RIC allo-SCT group (13% vs. 43%; P=0.06). With a median follow-up of 30 months, the probability of progression after transplantation at 5 years was 51% (95%CI, 39–73). Five-year overall survival (OS) was 26% (95%CI, 13–48). Most importantly, none of the pre-transplant parameters influenced OS or DFS. In all, these results suggest that standard allo-SCT is associated with a high TRM rate not allowing a breakthrough in the outcome of patients with secondary AML and high-risk MDS. The use of a RIC regimen significantly decreased TRM in this high risk group of patients, likely representing an attractive modality to develop novel strategies and further refine the allogeneic anti-leukemic activity for a better outcome.