Nonmyeloablative Haploidentical Transplant Followed by MLN9708

Summary

In an attempt to reduce relapse risk and improve outcomes following haploidentical transplantation for patients with high risk hematologic malignancies, the investigators will implement several strategies to augment the well documented effect of NK cell alloreactivity seen in HLA-mismatched transplantation. These strategies include (1) choosing potential haploidentical donors for optimal NK-alloreactivity, (2) utilizing proteasome inhibition post-transplant with MLN9708 to both sensitize tumor cells to NK cytotoxicity and protect against graft-versus-host disease (GVHD), and (3) eliminating mycophenolate mofetil from the post-transplant immunosuppression regimen to improve NK cell reconstitution following haploidentical peripheral blood stem cell transplantation.

Timeline

Start

2014-07-15

Primary completion

2020-07-28

Completion

2020-07-28

Publications

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• Background Ohata K, Espinoza JL, Lu X, Kondo Y, Nakao S. Mycophenolic acid inhibits natural killer cell proliferation and cytotoxic function: a possible disadvantage of including mycophenolate mofetil in the graft-versus-host disease prophylaxis regimen. Biol Blood Marrow Transplant. 2011 Feb;17(2):205-13. doi: 10.1016/j.bbmt.2010.08.014. Epub 2010 Aug 22.
• Solomon SR, Solh M, Zhang X, Brown S, Jackson KC, Holland HK, Morris LE, Bashey A. Prospective phase 2 trial of ixazomib after nonmyeloablative haploidentical peripheral blood stem cell transplant. Blood Adv. 2020 Aug 11;4(15):3669-3676. doi: 10.1182/bloodadvances.2020001958.

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