A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome

We investigated the feasibility and efficacy of a fludarabine-based dose-re duced conditioning regimen followed by stem cell transplantation from relat ed (n = 5) or unrelated HLA-matched donors (n = 7) in 12 patients with high risk MDS, who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine 30 mg/m(2) daily for 6 days, busulfan 4 mg/kg daily for 2 days and anti-thymocyte globulin (ATG, rabbit) 10 mg/kg daily for 4 days in 11 patients, while one patient r eceived fludarabine, ATG, cyclophosphamide and thiotepa. Graft-versus-host disease prophylaxis consisted of cyclosporine and a short course of methotr exate. The median age of the patients was 53 years (range 37-59). The media n percentage of blasts in bone marrow aspirate at transplantation was 15% ( range <5% to 35%). Diagnosis at transplant was RA (n = 1), RAEB (n = 5), RA EB-T (n = 5) and sAML (n = 1). A complex karyotype including monosomy 7 was noted in five patients. The reasons for using a dose-reduced conditioning regimen were prior autologous/syngeneic BMT (n = 4), active fungal infectio n (n = 2) or age/reduced performance status (it = 6). Engraftment was obser ved in all patients with complete donor chimerism. The incidence of acute G VHD (grade II-IV) was 33%. Eight patients died during follow-up due to rela pse (n = 4), liver toxicity (n = 2), aspergillus (n = 1) or aGVHD grade IV (n = 1). After a median follow-up of 19 months, the 2-year estimated diseas e-free survival is 12% (95% Cl: 2-23%) and the overall survival is 26% (95% CI: 4-52%). Fludarabine dose-reduced conditioning prior to allogeneic stem cell transplantation in high risk MDS patients, who were not eligible for standard transplantation, resulted in stable engraftment with complete chim erism, but the toxicity and relapse rate were considerable.