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Blood, 29 October 2009, Vol. 114, No. 18, pp. 3956-3959.
Prepublished online as a Blood First Edition Paper on August 27, 2009; DOI 10.1182/blood-2009-07-231092.


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TRANSPLANTATION

Brief report

Bortezomib, tacrolimus, and methotrexate for prophylaxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors

John Koreth1, Kristen E. Stevenson2, Haesook T. Kim2, Michael Garcia1, Vincent T. Ho1, Philippe Armand1, Corey Cutler1, Jerome Ritz1, Joseph H. Antin1, Robert J. Soiffer1, and Edwin P. Alyea, III1

1 Division of Hematologic Malignancies and 2 Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA

Graft-versus-host disease (GVHD) is a significant complication of allogeneic stem cell transplantation (alloSCT). The proteasome inhibitor bortezomib has immunomodulatory properties of potential benefit for GVHD control. We undertook a phase 1 trial of bortezomib, tacrolimus, and methotrexate for GVHD prophylaxis after reduced-intensity conditioning alloSCT using human leukocyte antigen–mismatched unrelated donors. Twenty-three patients were enrolled. Bortezomib dose levels of 1, 1.3, and 1.5 mg/m2 were evaluated with 5, 3, and 5 patients, respectively. Ten additional patients were accrued at the 1.3 mg/m2 bortezomib dose level. Bortezomib-related toxicity was minimal. With a 12-month median follow-up, grade II-IV acute GVHD occurred in 3 patients, a 180-day cumulative incidence of 13%. Chronic GVHD occurred in 9 patients, a 1-year cumulative incidence of 41%. At 1-year, the nonrelapse mortality was zero, cumulative incidence of relapse/progression was 29%, and overall, progression-free, and event-free survival were 75%, 64%, and 59%, respectively. Bortezomib is a promising novel immunomodulatory agent in allogeneic transplantation. This study was registered at http://www.clinicaltrials.gov as #NCT00369226 [ClinicalTrials.gov] .


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