Abstract
Hematopoietic stem cell transplantation (HSCT) recipients lacking HLA-matched related donors have increased graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). Bortezomib added to reduced-intensity conditioning can offer benefit in T cell-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 peripheral blood stem cell grafts. Median age was 49 years (range, 21 to 60), and median follow-up was 25 months (range, 11 to 36). The regimen was well tolerated. No dose modifications were required. Neutrophil and platelet engraftment occurred at a median of 14 (range, 10 to 33) and 17 (range, 10 to 54) days, respectively. Median 30-day donor chimerism was 99% (range, 90 to 100), and 100-day grades II to IV and III to 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 rates were 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 with 8/8 MUD MAC HSCT, and is suitable for randomized evaluation. (clinicaltrials.gov: NCT01323920.).
Original language | English (US) |
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Pages (from-to) | 1907-1913 |
Number of pages | 7 |
Journal | Biology of Blood and Marrow Transplantation |
Volume | 21 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2015 |
Bibliographical note
Funding Information:Financial disclosure: This study was supported in part by Millennium Pharmaceuticals Inc. and Otsuka Pharmaceuticals Inc. , the Jock and Bunny Adams Education and Research Endowment , and by the National Institutes of Health (grants CA183560 , CA183559 , and P01CA142106 ).
Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.
Keywords
- Allogeneic
- HLA mismatch
- Myeloablative
- Proteasome inhibitor
- T cell replete
- Transplantation