A Bortezomib-based Regimen Offers Promising Survival and Graft-vs.-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial

摘要

Hematopoietic stem cell transplantation (HSCT) recipients lacking HLA-matched related donors have increased graft-vs.-host disease (GVHD) and non-relapse mortality (NRM). Bortezomib added to reduced-intensity conditioning can offer benefit in T-replete HLA-mismatched HSCT, and may also benefit myeloablative conditioning (MAC) transplants. We conducted a phase II trial of short-course bortezomib plus standard tacrolimus/methotrexate after busulfan/fludarabine MAC in 34 patients with predominantly myeloid malignancies. Fourteen (41%) received 8/8 HLA-matched unrelated donor (MUD) and 20 (59%) received 7/8 HLA-mismatched related/unrelated donor (MMRD/MMUD) peripheral blood stem cell grafts. Median age was 49 years (range, 21–60) and median follow-up was 25 months (range, 11–36). The regimen was well tolerated. No dose-modifications were required. Neutrophil and platelet engraftment occurred at a median of 14 (range, 10–33) and 17 (range, 10–54) days respectively. Median 30-day donor chimerism was 99% (range, 90–100). 100-day grade II-IV and III-IV acute GVHD incidence was 32% and 12% respectively. One-year chronic GVHD incidence was 50%. Two-year cumulative incidence of both NRM and relapse was 16%. Two-year progression-free and overall survival was 70% and 71% respectively. Outcomes were comparable to an 8/8 MUD MAC cohort (n=45). Immune reconstitution was robust. Bortezomib-based MAC HSCT is well tolerated, with HLA-mismatched outcomes comparable to 8/8 MUD MAC HSCT, and is suitable for randomized evaluation.