Bortezomib beneficial in graft-versus-host disease prophylaxis

August 8, 2012
Bortezomib beneficial in graft-versus-host disease prophylaxis
Patients with hematologic malignancies undergoing an HLA-mismatched unrelated donor reduced-intensity conditioning hematopoietic stem cell transplantation may benefit from a prophylactic, short-course, bortezomib-based regimen to reduce the incidence of graft-versus-host disease, according to research published online Aug. 6 in the Journal of Clinical Oncology.

(HealthDay) -- Patients with hematologic malignancies undergoing an HLA-mismatched unrelated donor (MMUD) reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) may benefit from a prophylactic, short-course, bortezomib-based regimen to reduce the incidence of graft-versus-host disease (GVHD), according to research published online Aug. 6 in the Journal of Clinical Oncology.

John Koreth, M.B.B.S., D.Phil., of the Dana-Farber Cancer Institute in Boston, and colleagues conducted a prospective, phase I/II trial involving 45 patients who underwent MMUD RIC HSCT. Participants underwent a short-course GVHD prophylaxis regimen consisting of bortezomib administered on days one, four, and seven following peripheral stem cell infusion plus methotrexate and tacrolimus.

The researchers found that the cumulative incidence of grade 2 to 4 GVHD over 180 days was 22 percent and the one-year cumulative incidence was 29 percent for chronic GVHD. At two years, deaths due to relapse occurred in 38 percent, and nonrelapse mortality was 11 percent. Progression-free survival and overall survival were 51 and 64 percent, respectively, at two years. The rates of nonrelapse mortality, acute and chronic GVHD, and survival were similar to those of contemporaneous HLA-matched RIC HSCT.

"In conclusion, short-course, bortezomib-based GVHD prophylaxis appears safe and efficacious in HLA-mismatched RIC transplantation, with encouraging survival," the authors write. "Importantly, bortezomib-based MMUD transplantation achieved clinical outcomes comparable to HLA-matched transplantation, along with enhancement of various immune reconstitution parameters."

One author disclosed financial ties to Millennium Pharmaceuticals, which partially funded the study and develops and markets .

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