ArticleBlood advances2023
Posttransplantation cyclophosphamide expands functional myeloid-derived suppressor cells and indirectly influences Tregs.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 30 citations in OpenAlex.
- Trial
- A Phase II Trial to Evaluate the Safety and Immunogenicity of Two Doses of a Folate Receptor Alpha Vaccine in Patients with Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Islets co-engineered with thrombomodulin and CD47 achieve sustained survival in allogeneic recipients without chronic immunosuppression.JCI insight · 2026Article
- Hybrid Systems Modeling of Donor T-Cell Responses and Graft-Versus-Host-Disease After Posttransplantation Cyclophosphamide Administration.CPT: pharmacometrics & systems pharmacology · 2026Article
- Monocytic Cell Variations in Postallotransplant Environment: Balancing Graft Versus Host Disease and Graft-Versus-Leukemia Effect.Journal of immunology research · 2026Review
- Myeloid-Derived Suppressor Cells: Immunoregulatory Roles and Therapeutic Prospects in Immune-Mediated Hematological Disorders.Journal of immunology research · 2026Review
- Article
- Unrelated Donor Age and Recipient Outcomes After Posttransplant Cyclophosphamide vs Conventional Prophylaxis.JAMA oncology · 2025Article
- Post-transplantation cyclophosphamide and antithymocyte globulin in 8/10 HLA-mismatched unrelated donor transplantation: the analysis on behalf of the transplant complications working party of the EBMT.Bone marrow transplantation · 2025Article
- Therapeutic effects of curcumin nanoemulsion on cyclophosphamide-induced testicular toxicity in adult male mice.Clinical and experimental reproductive medicine · 2025Article
- Optimal GVHD Prophylaxis.Advances in experimental medicine and biology · 2025Review
- Safety but limited efficacy of donor lymphocyte infusion for post-transplantation cyclophosphamide-treated patients.Bone marrow transplantation · 2024Article
- Lower incidence of acute graft-versus-host disease with post-transplantation cyclophosphamide compared to anti-thymocyte globulin in higher-risk myelodysplastic syndrome.Bone marrow transplantation · 2024Article
- Outcomes of Human Leukocyte Antigen-Matched Related Donor and Haploidentical Allogeneic Hematopoietic Cell Transplantation Recipients by Immune Profiles of Recipients and Donors.Transplantation and cellular therapy · 2024Article
- Post-Transplant Cyclophosphamide Combined with Brilliant Blue G Reduces Graft-versus-Host Disease without Compromising Graft-versus-Leukaemia Immunity in Humanised Mice.International journal of molecular sciences · 2024Article
- Review
- Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation.Frontiers in immunology · 2024Article
- Age and dose dependent changes to the bone and bone marrow microenvironment after cytotoxic conditioning with busulfan.Frontiers in cell and developmental biology · 2024Article
- The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally.Hematology. American Society of Hematology. Education Program · 2023Article
- Relapse after allogeneic transplantation with post-transplant cyclophosphamide: Shattering myths and evolving insight.Blood reviews · 2023Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Posttransplantation cyclophosphamide (PTCy), given on days +3 and +4, reduces graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), but its immunologic underpinnings are not fully understood. In a T-cell-replete, major histocompatibility complex-haploidentical murine HCT model (B6C3F1→B6D2F1), we previously showed that PTCy rapidly induces suppressive mechanisms sufficient to prevent GVHD induction by non-PTCy-exposed donor splenocytes infused on day +5. Here, in PTCy-treated mice, we found that depleting Foxp3+ regulatory T cells (Tregs) in the initial graft but not the day +5 splenocytes did not worsen GVHD, yet depleting Tregs in both cellular compartments led to fatal GVHD induced by the day +5 splenocytes. Hence, Tregs were necessary to control GVHD induced by new donor cells, but PTCy's impact on Tregs appeared to be indirect. Therefore, we hypothesized that myeloid-derived suppressor cells (MDSCs) play a complementary role. Functionally suppressive granulocytic and monocytic MDSCs were increased in percentages in PTCy-treated mice, and MDSC percentages were increased after administering PTCy to patients undergoing HLA-haploidentical HCT. PTCy increased colony-stimulating factors critical for MDSC development and rapidly promoted the generation of MDSCs from bone marrow precursors. MDSC reduction via anti-Gr1 treatment in murine HCT did not worsen histopathologic GVHD but resulted in decreased Tregs and inferior survival. The clinical implications of these findings, including the potential impact of expanded MDSCs after PTCy on engraftment and cytokine release syndrome, remain to be elucidated. Moreover, the indirect effect that PTCy has on Tregs, which in turn play a necessary role in GVHD prevention by initially transplanted or subsequently infused T cells, requires further investigation.
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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.