Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning

The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control. Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4. The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019). This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors.