High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease
Leo Luznik, Javier Bolaños-Meade, Marianna Zahurak, Allen R Chen, B Douglas Smith, Robert Brodsky, Carol Ann Huff, Ivan Borrello, William Matsui, Jonathan D Powell, Yvette Kasamon, Steven N Goodman, Allan Hess, Hyam I Levitsky, Richard F Ambinder, Richard J Jones, Ephraim J Fuchs, Leo Luznik, Javier Bolaños-Meade, Marianna Zahurak, Allen R Chen, B Douglas Smith, Robert Brodsky, Carol Ann Huff, Ivan Borrello, William Matsui, Jonathan D Powell, Yvette Kasamon, Steven N Goodman, Allan Hess, Hyam I Levitsky, Richard F Ambinder, Richard J Jones, Ephraim J Fuchs
Abstract
Because of its potent immunosuppressive yet stem cell-sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)-matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell-replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017).
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Source: PubMed