Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2019 May 6;129(6):2189-2191.
doi: 10.1172/JCI128710.

Mechanism of action of posttransplantation cyclophosphamide: more than meets the eye

Vedran Radojcic  1 , Leo Luznik  2
Affiliations
Comment

Mechanism of action of posttransplantation cyclophosphamide: more than meets the eye

Vedran Radojcic et al. J Clin Invest. .

Abstract

For high-risk and refractory hematological malignancies, allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only available curative therapy, with benefits derived from the antigenic disparity between recipient cancer and the incoming immune system. This immunologic mismatch can also lead to lethal graft-versus-host disease (GVHD), and immunosuppression strategies, including high-dose posttransplantation cyclophosphamide (PTCy), have been developed to allow for safe alloHSCT delivery. In this issue of JCI, Wachsmuth et al. present the results of preclinical studies designed to evaluate the mechanisms that underlie efficacy of PTCy after alloHSCT. The results of this study challenge previous reports indicating that alloreactive T cell elimination and thymic clonal deletion are primary mediators of PTCy efficacy and provide strong evidence to support FoxP3+CD4+ Tregs as important effectors of PTCy benefits.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: LL receives research support from Genentech and Merck and has a patent licensed to WindMIL Therapeutics (WO2014085437A2).

Comment on

References

    1. Luznik L, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641–650. doi: 10.1016/j.bbmt.2008.03.005. - DOI - PMC - PubMed
    1. McCurdy SR, et al. Grade II acute graft-versus-host disease and higher nucleated cell graft dose improve progression-free survival after HLA-haploidentical transplant with post-transplant cyclophosphamide. Biol Blood Marrow Transplant. 2018;24(2):343–352. doi: 10.1016/j.bbmt.2017.10.023. - DOI - PMC - PubMed
    1. Luznik L, et al. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010;115(16):3224–3230. doi: 10.1182/blood-2009-11-251595. - DOI - PMC - PubMed
    1. Kanakry CG, et al. Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood. 2014;124(25):3817–3827. doi: 10.1182/blood-2014-07-587477. - DOI - PMC - PubMed
    1. Mielcarek M, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502–1508. doi: 10.1182/blood-2015-10-672071. - DOI - PMC - PubMed

Publication types

Substances