Standard myeloablative conditioning prior to allogeneic hematopoietic stem cell (HSC) transplantation has been associated with significant toxicity in patients older than 45 years of age with myelofibrosis with myeloid metaplasia (MMM). We sought to evaluate the efficacy of a reduced-intensity conditioning regimen for allogeneic HSC transplantation in this setting. A regimen consisting of fludarabine (30 mg/m(2) intravenously daily for 5 days) and melphalan (70 mg/m(2) intravenously daily for 2 days) followed by transplantation of filgrastim-mobilized peripheral blood cells from HLA-identical siblings was administered to 4 older patients (median age, 56 years; range, 48-58 years) with advanced MMM. All patients achieved prompt neutrophil and platelet engraftment and have experienced a significant regression of splenomegaly and bone marrow fibrosis. All now have normal bone marrow cellularity. With a median follow-up of 13 months (range, 11-19 months), all 4 patients are alive with stable full-donor hematopoietic chimerism. These results support the feasibility and effectiveness of reduced-intensity conditioning prior to allogeneic HSC transplantation for older patients with advanced MMM.