ArticleThe Journal of clinical investigation2019
Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
191 citing papers in PubMed, 4 syntheses or guidelines pooled it, 276 citations in OpenAlex.
- Systematic overview of HLA-matched allogeneic hematopoietic cell transplantation with post-transplantation cyclophosphamide.International journal of hematology · 2022Pooled it
- Post-transplant cyclophosphamide versus antithymocyte globulin in allogeneic hematopoietic cell transplantation: a meta-analysis.Annals of hematology · 2021Pooled it
- Pooled it
- Haploidentical Hematopoietic Stem Cell Transplantation Versus Umbilical Cord Blood Transplantation in Hematologic Malignancies: A Systematic Review and Meta-Analysis.Cell transplantationPooled it
- Excellent outcomes using a novel reduced intensity conditioning with thiotepa and post-transplant cyclophosphamide for HLA-matched related donor transplant in adolescents and adults with sickle cell disease.Bone marrow transplantation · 2026Trial
- Intermediate-dose posttransplantation cyclophosphamide for myeloablative HLA-haploidentical bone marrow transplantation.Blood advances · 2025Trial
- Trial
- Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil.Transplantation and cellular therapy · 2023Trial
- Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial.Blood advances · 2022Trial
- Trial
- National Marrow Donor Program-Sponsored Multicenter, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation Using Post-Transplant Cyclophosphamide.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis.Blood · 2021Trial
- The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) Score for HLA Class I Graft-versus-Host Disparity Is Associated with Increased Acute Graft-versus-Host Disease in Haploidentical Transplantation with Post-Transplantation Cyclophosphamide.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020Trial
- Post-Transplant Bendamustine as a Platform for Immune Modulation After Allogeneic Hematopoietic Cell Transplantation.European journal of haematology · 2026Review
- Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.Nature immunology · 2026Article
- Early inflammatory complications after haploidentical hematopoietic stem cell transplantation with post transplant cyclophosphamide for acute leukemia: a pediatric multicenter experience.Bone marrow transplantation · 2026Article
- PTCy-Based versus ATG-Based GVHD Prophylaxis in Mismatched Unrelated Donor HCT: A Secondary Analysis of CIBMTR Data.Transplantation and cellular therapy · 2026Article
- Are all mismatched donors the same in allogeneic hematopoietic cell transplantation for secondary acute myeloid leukemia in the posttransplant cyclophosphamide era?Bone marrow transplantation · 2026Article
- Fludarabine, cyclophosphamide and 2 Gy TBI with PT-Cy as a single platform for haplo and unrelated donor allo-SCT in older AML or MDS patients.Bone marrow transplantation · 2026Article
- Early Secondary Graft Failure After Complete Donor Chimerism with Autologous Recovery Following Haploidentical HSCT for Relapsed B-ALL.Blood cell therapy · 2026Article
131 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-transplantation cyclophosphamide (PTCy) recently has had a marked impact on human allogeneic hematopoietic cell transplantation (HCT). Yet, our understanding of how PTCy prevents graft-versus-host disease (GVHD) largely has been extrapolated from major histocompatibility complex (MHC)-matched murine skin allografting models that were highly contextual in their efficacy. Herein, we developed a T-cell-replete, MHC-haploidentical, murine HCT model (B6C3F1→B6D2F1) to test the putative underlying mechanisms: alloreactive T-cell elimination, alloreactive T-cell intrathymic clonal deletion, and suppressor T-cell induction. In this model and confirmed in four others, PTCy did not eliminate alloreactive T cells identified using either specific Vβs or the 2C or 4C T-cell receptors. Furthermore, the thymus was not necessary for PTCy's efficacy. Rather, PTCy induced alloreactive T-cell functional impairment which was supported by highly active suppressive mechanisms established within one day after PTCy that were sufficient to prevent new donor T cells from causing GVHD. These suppressive mechanisms included the rapid, preferential recovery of CD4+CD25+Foxp3+ regulatory T cells, including those that were alloantigen-specific, which served an increasingly critical function over time. Our results prompt a paradigm-shift in our mechanistic understanding of PTCy. These results have direct clinical implications for understanding tolerance induction and for rationally developing novel strategies to improve patient outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.