Short Course of Post-Transplantation Cyclophosphamide and Bortezomib for Graft-versus-Host Disease Prevention after Allogeneic Peripheral Blood Stem Cell Transplantation Is Feasible and Yields Favorable Results: A Phase I Study

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Ahmad-Samer Al-HomsiAly Mageed

Abstract

An effective graft-versus-host disease (GVHD) preventative approach that preserves the graft-versus-tumor effect after allogeneic hematopoietic stem cell transplantation (HSCT) remains elusive. Standard GVHD prophylactic regimens suppress T cells indiscriminately and are suboptimal. Conversely, post-transplantation high-dose cyclophosphamide selectively destroys proliferating alloreactive T cells, allows the expansion of regulatory T cells, and induces long-lasting clonal deletion of intrathymic antihost T cells. It has been successfully used to prevent GVHD after allogeneic HSCT. Bortezomib has antitumor activity on a variety of hematological malignancies and exhibits a number of favorable immunomodulatory effects that include inhibition of dendritic cells. Therefore, an approach that combines post-transplantation cyclophosphamide and bortezomib seems attractive. Herein, we report the results of a phase I study examining the feasibility and safety of high-dose post-transplantation cyclophosphamide in combination with bortezomib in patients undergoing allogeneic peripheral blood HSCT from matched siblings or unrelated donors after reduced-intensity conditioning. Cyclophosphamide was given at a fixed dose (50 mg/kg on days +3 an...Continue Reading

References

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Citations

May 18, 2016·International Journal of Hematologic Oncology·Erin Gatza, Sung Won Choi
Jul 23, 2016·Expert Review of Hematology·Rebecca CitrinDavid T Teachey
Sep 17, 2018·Immunogenetics·Michael BaslerMarcus Groettrup
Mar 19, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Jiaxin LinColin C Anderson
Nov 7, 2019·Bone Marrow Transplantation·Emi YokoyamaTakanori Teshima

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