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Post-transplantation cyclophosphamide for chimerism-based tolerance

Bone Marrow Transplantation volume 54, pages 769–774 (2019)Cite this article

Abstract

High-dose cyclophosphamide given post-transplant (PTCy) successfully enables tolerance induction in HLA-mismatched related blood or marrow transplantation (haploBMT) manifested by low rates of graft failure, severe acute graft-versus-host disease (GVHD), and chronic GVHD. When proceeded by nonmyeloablative conditioning, PTCy has also been associated with a low incidence of nonrelapse mortality. The safety of this platform has garnered interest in expanding its use to non-malignant indications for allogeneic blood or marrow transplantation (alloBMT). After success in a preliminary Phase I/II trial, use of a PTCy-based haploBMT platform is now being explored in a large Blood and Marrow Transplant Clinical Trials Network (BMT CTN) study for sickle cell disease. These emerging data in patients with hemoglobinopathies provided the rationale for exploring the use of PTCy in combined solid organ and BM transplantation as a means of tolerance induction through donor hematopoietic chimerism with a goal to obviate the need for a lifetime of immunosuppression. Several case reports, series, and small clinical trials have now been published of combined solid organ and alloBMT in patients with hematologic malignancies who had organ failure that would have been preclusive of alloBMT in the absence of solid organ transplantation. Here we will review the pre-clinical and clinical studies supporting the use of PTCy for chimerism-based tolerance induction.

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Funding

Publication of this supplement was sponsored by Gilead Sciences Europe Ltd, Cell Source, Inc., The Chorafas Institute for Scientific Exchange of the Weizmann Institute of Science, Kiadis Pharma, Miltenyi Biotec, Celgene, Centro Servizi Congressuali, Almog Diagnostic.

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Authors and Affiliations

  1. Abramson Cancer Center and the Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Shannon R. McCurdy

  2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Leo Luznik MD

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  1. Shannon R. McCurdy
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Correspondence to Shannon R. McCurdy.

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Conflict of interest

SRM received grant support from American Cancer Society Institutional Research Grant (ACS IRG) and served as PI for 129784-IRG-16-188-38-IRG. LL has received consulting fees from Pharmacyclics and Abbivie, lecture fees from Merck, grant support from Gennetech, and receives patent royalties on alloMILs (WindMill Therapheutics).

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McCurdy, S.R., Luznik, L. Post-transplantation cyclophosphamide for chimerism-based tolerance. Bone Marrow Transplant 54 (Suppl 2), 769–774 (2019). https://doi.org/10.1038/s41409-019-0615-0

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