Post-transplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation.

Publication Type:

Journal Article


Blood (2016)


The cumulative incidence of NIH-defined chronic GVHD requiring systemic treatment is approximately 35% at one year after transplantation of G-CSF-mobilized blood cells from HLA-matched related or unrelated donors. We hypothesized that high-dose cyclophosphamide given after G-CSF-mobilized blood cell transplantation would reduce the cumulative one-year incidence of chronic GVHD to 15% or less. Forty-three patients with high-risk hematologic malignancies (median age, 43 years) were enrolled between December 2011 and September 2013. Twelve (28%) received grafts from related donors, and 31 (72%) received grafts from unrelated donors. Pretransplant conditioning consisted of fludarabine and targeted busulfan (n=25) or total body irradiation (≥12Gy; n=18). Cyclophosphamide was given at 50 mg/kg/day on days 3 and 4 after transplantation, followed by cyclosporine starting on day 5. In the absence of acute GVHD, cyclosporine doses were tapered from day 56 through day 126. The cumulative one-year incidence of NIH-defined chronic GVHD was 16% (95% CI, 5% to 28%). The cumulative incidence estimates of grades II-IV and III-IV acute GVHD were 77% and 0%, respectively. At 2 years, the cumulative incidence estimates of non-relapse mortality and recurrent malignancy were 14% and 17%, respectively, and overall survival was projected at 70%. Of the 42 patients followed for at least one year, 21 (50%) were relapse-free and alive without systemic immunosuppression at 1 year after HCT. Thus, myeloablative pretransplant conditioning can be safely combined with high-dose cyclophosphamide after transplantation, and the risk of chronic GVHD associated with HLA-matched mobilized blood cell grafts can be substantially reduced. Registered NCT01427881.