GVHD prophylaxis with single-agent cyclophosphamide effective after allogeneic transplant
Post-transplant graft-versus-host disease prophylaxis with single-agent cyclophosphamide appeared safe and effective in patients who underwent conditioning with busulfan and fludarabine prior to allogeneic bone marrow transplantation, according to results of a multi-institutional study.
Several single-institution studies have demonstrated the safety and efficacy of conditioning with IV busulfan (Busulfex, Otsuka Pharmaceutical) and fludarabine, as well as the benefits of graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide.
In the current study, Christopher G. Kanakry, MD, of Johns Hopkins Kimmel Cancer Center, and colleagues assessed whether the clinical efficacy of the two techniques would be maintained when they were combined.
The analysis included 92 patients with high-risk leukemias or myeloid malignancies; of them, 45 received related allografts and 47 received unrelated allografts.
All patients received IV busulfan and fludarabine 2 to 5 days prior to bone marrow transplantation. Patients also received cyclophosphamide 50 mg/kg daily on days 3 and 4 after transplantation.
Median follow-up was 2.2 years.
Researchers observed grade 2 to grade 4 GVHD in 51% of patients, grade 3 to grade 4 in 15% of patients, and chronic GVHD in 14% of patients.
Nonrelapse mortality rates were 9% at 100 days post-transplant and 16% at 1 year post-transplant. The researchers reported 2-year DFS of 62% and 2-year OS of 67%.
Donor relatedness did not affect nonrelapse mortality, DFS or OS, Kanakry and colleagues wrote.
Patients in complete remission without evidence of minimal residual disease exhibited noticeably superior DFS and OS than patients in complete remission with minimal residual disease or those with active disease at the time of transplantation (P=.0005 for DFS; P=.019 for OS).
The results are even more compelling based on the fact GVHD prophylaxis with cyclophosphamide lasts only 2 days. Traditionally, most transplant patients undergo 6 months of immunosuppression to reduce risk for GVHD.
“The lack of a requirement for immunosuppression in a significant subset of patients can facilitate the early integration of adjunct therapies to prevent relapse,” Kanakry and colleagues wrote. “As [post-transplantation cyclophosphamide] is a promising strategy for GVHD prophylaxis in both HLA-matched and HLA-mismatched [allogeneic bone marrow transplantation], its efficacy relative to other approaches requires further study through randomized clinical trials.”
Disclosure: The researchers report research funding and consultant/advisory roles with Otsuka Pharmaceuticals and Sanofi-Aventis.