Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation:: Chronic graft-versus-host disease is the strongest factor improving survival

Purpose Reduced-intensity conditioning ( RIC) for allogeneic stem-cell transplantation ( allo-SCT) reduces nonrelapse mortality ( NRM). This reduction makes it possible for patients who are ineligible for high-dose myeloablative conditioning allo-SCT to benefit from graft-versus-leukemia reaction. In this multicenter, prospective study of patients with acute myeloid leukemia ( AML) and high-risk myelodysplastic syndrome ( MDS), we investigated the efficacy of RIC allo-SCT from a human leukocyte antigen-identical sibling by using a regimen that uses fludarabine and busulfan. Patients and Methods Ninety-three patients with AML ( n = 59) and MDS ( n = 34) were included, and the median age was of 53 years. Follow-up for survivors was 43 months ( range, 3 to 89 months). The conditioning regimen consisted of fludarabine ( 150 mg/m(2)) and oral busulfan ( 8 to 10 mg/kg). All except one patient received mobilized peripheral blood stem cells. Graft-versus-host disease ( GVHD) prophylaxis consisted of cyslosporine and methotrexate or mycophenolate mofetil. Results The 100-day, 1-year, and 4-year incidences of NRM were 8, 16%, and 21%, respectively. The 1- and 4-year relapse cumulative incidences were 23% and 37%, respectively, and leukemia recurrence was the main cause of death. The 4-year disease-free survival ( DFS) and overall survival ( OS) rates were 43% and 45%, respectively. The 4-year cumulative incidence of chronic GVHD was 53% ( 45% extensive), and its development was the major factor associated with lower relapse incidence and improved DFS and OS. Conclusion Our results confirm the capacity of this RIC regimen to obtain long-term remissions in patients ineligible for a conventional allo-SCT. The results suggest an important role of the development of chronic GVHD in reducing relapse and improving DFS and OS.