This prospective trial assessed the safety and efficacy of allogeneic hematopoietic stem cell transplantation from a HLA-matched donor with a reduced-intensity regimen (RIST) consisting of iv fludarabine 30 mg/m 2 for 6 days and oral busulfan 4 mg/kg/day for 2 days in patients older than 50 years with hematological malignancies. Cyclosporine alone or cyclosporine with short-term methotrexate was randomized for graft-versus-host disease prophylaxis. After 30 patients had been enrolled, an interim analysis was performed, and this report focuses on a precise evaluation of the toxicity profile and chimerism kinetics. Sustained engraftment in all patients, no severe regimen-related toxicity (RRT) within 20 days, and no transplant-related mortality through Day 100 were observed. T-cell (CD3+) full-donor (over 90%) chimerism was observed in 22 of the 30 patients, while the remaining eight had mixed-donor chimerism over 77% on Day 90. Thereafter, five subsequently converted to full-donor chimerism without donor lymphocyte infusion by day 120 (n = 4) or Day 180 (n = 1). Two showed persistent mixed chimerism without relapse through Day 180. Grade III-IV acute graft-versus-host disease and extensive chronic graft-versus-host disease occurred in 10% and 73%, respectively. With a median follow-up of 1.5 years, overall survival and disease-free survival at 1 year was 83% and 62%, respectively. Seven patients hematologically relapsed overall, and five of them had myelodysplastic syndrome with poor prognostic factors. In older patients, RIST with fludarabine and busulfan was associated with acceptable toxicities and a satisfactory antileukemia effect, regardless of the early chimerism status.
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