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Commentary 10.1172/JCI128710

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

Vedran Radojcic1 and Leo Luznik2

1Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, Utah, USA.

2Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.

Address correspondence to: Vedran Radojcic, University of Utah Huntsman Cancer Institute, Room 5263, 2000 Cir of Hope Drive, Salt Lake City, Utah 84105, USA. Phone: 801.213.6109; Email: vedran.radojcic@hsc.utah.edu. Or to: Leo Luznik, Johns Hopkins University, Cancer Research Building I, Room 2M88, 1650 Orleans Street, Baltimore, Maryland 21231, USA. Phone: 410.502.7732; Email: luznile@jhmi.edu.

Find articles by Radojcic, V. in: JCI | PubMed | Google Scholar |

1Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, Utah, USA.

2Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.

Address correspondence to: Vedran Radojcic, University of Utah Huntsman Cancer Institute, Room 5263, 2000 Cir of Hope Drive, Salt Lake City, Utah 84105, USA. Phone: 801.213.6109; Email: vedran.radojcic@hsc.utah.edu. Or to: Leo Luznik, Johns Hopkins University, Cancer Research Building I, Room 2M88, 1650 Orleans Street, Baltimore, Maryland 21231, USA. Phone: 410.502.7732; Email: luznile@jhmi.edu.

Find articles by Luznik, L. in: JCI | PubMed | Google Scholar

First published May 6, 2019 - More info

Published in Volume 129, Issue 6 on June 3, 2019
J Clin Invest. 2019;129(6):2189–2191. https://doi.org/10.1172/JCI128710.
© 2019 American Society for Clinical Investigation
First published May 6, 2019 - Version history

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.

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