Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802.

Corticosteroids are the accepted primary therapy for acute graft-versus-host disease (GVHD), but durable responses are seen in only about half of the patients. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0802, a phase 3 multicenter randomized double-blinded trial, was designed to test whether mycophenolate mofetil (MMF) plus corticosteroids was superior to corticosteroids alone as initial therapy for acute GVHD. Patients with newly diagnosed acute GVHD were eligible if they required systemic therapy. Patients were randomized to receive prednisone with either MMF or placebo. The primary end point was acute or chronic GVHD-free survival at day 56 after initiation of therapy. A futility rule for GVHD-free survival at day 56 was met at a planned interim analysis after 235 patients (of 372) were enrolled: 116 MMF, 119 placebo. Baseline characteristics were well balanced between treatment groups including grade and organ distribution of GVHD. GVHD-free survival at day 56, cumulative incidence of chronic GVHD at 12 months, overall survival, Epstein-Barr virus reactivation, severe, life-threatening infections, relapse at 12 months, and quality of life were similar. The addition of MMF to corticosteroids as initial therapy for acute GVHD does not improve GVHD-free survival compared with corticosteroids alone. This trial was registered at www.clinicaltrials.gov as #NCT01002742.

Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies.

Two parallel phase II trials in adults with hematologic malignancies demonstrated comparable survival after reduced-intensity conditioning and transplantation of either 2 HLA-mismatched umbilical cord blood (UCB) units or bone marrow from HLA-haploidentical relatives. Donor choice is often subject to physician practice and institutional preference. Despite clear preliminary evidence of equipoise between HLA-haploidentical related donor and double unrelated donor UCB transplantation, the actual prospect of being randomized between these 2 very different donor sources is daunting to patients and their treating physicians alike. Under these circumstances, it is challenging to conduct a phase III randomized trial in which patients are assigned to the UCB or haploidentical bone marrow arms. Therefore, we aimed to provide an evidence-based review and recommendations for selecting donors for adults without an HLA-matched sibling or an HLA-matched adult unrelated donor.