Evidence map›Paper›PMID 40061351›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant.

Steven J Siegel, Susan DeWolf, Joseph Schmalz, Wael Saber, Jiayi Dong, Michael J Martens, Brent Logan, Alexandre Albanese, Lorenzo Iovino, Edward Chen and 46 more

Registry-linked trialAbstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03959241 (A Randomized, Multicenter, Phase III Trial of Tacrolimus/Methotrexate Versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

NCT03959241 phase3completednot on this map

A Randomized, Multicenter, Phase III Trial of Tacrolimus/Methotrexate Versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation (BMT CTN 1703; Progress III); Companion Study: Microbiome and Immune Reconstitution in Cellular Therapies and Hematopoietic Stem Cell Transplantation (BMT CTN 1801; Mi-Immune)

TypeinterventionalSponsorMedical College of WisconsinRan2019 to 2022Enrolled431ConditionsAcute Leukemia, Chronic Myelogenous Leukemia (CML), Myelodysplasia, LymphomaArmsMobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate, Tacrolimus, Methotrexate, Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide, Mycophenolate Mofetil
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

56 authors.

Steven J SiegelDepartment of Pediatrics, Harvard Medical School and Divisions of Infectious Diseases and Hematology/Oncology, Boston Children's Hospital, Boston, MA.ORCID 0000-0003-0690-2390
Susan DeWolfLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Joseph SchmalzAdaptive Biotechnologies, Seattle, WA.
Wael SaberDepartment of Medicine, Medical College of Wisconsin and Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI.
Jiayi DongDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
Michael J MartensCIBMTR and Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI.ORCID 0000-0003-3799-681X
Brent LoganCIBMTR and Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI.
Alexandre AlbaneseDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
Lorenzo IovinoClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Edward ChenDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
James KaminskiDivision of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA and the Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA.ORCID 0000-0002-5137-7516
Donna NeubergDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA.
Kyle HebertDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA.
Paula KeskulaDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
Jillian ZavistaskiDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
Lea SteinbergDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
Isabella SchichterDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
Lorenzo CagninDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
Vanessa HernandezTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.
Makya WarrenTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.
Kristy ApplegateEmmes, Rockville, MD.
Merav BarClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Saurabh ChhabraDivision of Hematology/Oncology, Mayo Clinic, Phoenix, AZ.
Sung Won ChoiDepartment of Pediatrics, University of Michigan, Ann Arbor, MI.
William ClarkDivision of Hematology-Oncology and Palliative Care, Virginia Commonwealth University, Richmond, VA.
Suman DasDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
Robert JenqDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.
Richard J JonesSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
John E LevineTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Hemant MurthyDivision of Hematology-Oncology and Blood and Marrow Transplant and Cellular Therapy Programs, Mayo Clinic, Jacksonville, FL.
Armin RashidiClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Marcie RichesCIBMTR, Milwaukee, WI.
Karamjeet SandhuDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.
Anthony D SungDivision of Hematologic Malignancies and Cellular Therapy, Kansas University Medical Center, Kansas City, KS.
Karilyn LarkinOhio State University Comprehensive Cancer Center, Columbus, OH.
Monzr M Al MalkiDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.
Mahasweta GooptuDepartment of Hematology and Oncology, Dana-Farber Cancer Institute, Boston, MA.
Hany ElmariahDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer and Research Institute, Tampa, FL.
Amin AlousiDepartment of Stem Cell Transplantation and Cellular Therapy, the University of Texas M.D. Anderson Cancer Center, Houston, TX.
Lyndsey RunaasDivision of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI.
Brian ShafferAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College, New York, NY.
Andrew RezvaniDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA.
Najla El JurdiCenter for Cancer Research, National Cancer Institute, Bethesda, MD.
Alison W LorenDivision of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Danielle ScheffeyAdaptive Biotechnologies, Seattle, WA.
Catherine SandersAdaptive Biotechnologies, Seattle, WA.
Mehdi HamadaniBlood and Marrow Transplant Program and Cellular Therapy Program, Medical College of Wisconsin and CIBMTR, Milwaukee, WI.
Jarrod DudakovTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center and Department of Immunology, University of Washington, Seattle, WA.ORCID 0000-0001-6220-5632
Stephanie BienAdaptive Biotechnologies, Seattle, WA.
Harlan RobinsAdaptive Biotechnologies, Seattle, WA.
Mary HorowitzBlood and Marrow Transplant Program and Cellular Therapy Program, Medical College of Wisconsin and CIBMTR, Milwaukee, WI.
Javier Bolaños-MeadeSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
Shernan HoltanBlood and Marrow Transplantation Section, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Ami S BhattDivision of Hematology, Departments of Medicine and Genetics, Stanford University, Palo Alto, CA.ORCID 0000-0001-8099-2975
Miguel-Angel PeralesAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College, New York, NY.
Leslie S KeanDepartment of Pediatrics, Harvard Medical School, Division of Hematology/Oncology, Boston Children's Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.

Funding

Blood and Marrow Transplant Clinical Trials Network DCC- The Medical College of Wisconsin, Inc.U24HL138660 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Steven M. DeVine, Mehdi Hussain Hamadani · 2017 to 2026
$71.4M
Easy-to-read Informed Consent for HCT Clinical TrialsU10HL069294 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HOROWITZ, MARY MARESCA · 2011 to 2016
$43.8M
Single Cell Analysis and ImmunogeneticsP01HL158505 · NHLBI · DANA-FARBER CANCER INST · PI Corey S Cutler · 2022 to 2026
$15.3M
Novel Biologic Therapies for GVHDR01HL095791 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI KEAN, LESLIE S · 2010 to 2025
$13.3M
Optimizing HCT Outcomes: A Multi-omic InvestigationR01HL181969 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Ami Siddharth Bhatt, Leslie S Kean · 2025 to 2026
$3.9M
MSKCC BMT CTN RenewalUG1HL069315 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI MIGUEL-ANGEL PERALES · 2017 to 2026
$2.2M
Core Clinical Centers for the Blood and Marrow Transplant Clinical Trials Network (UG1)UG1HL108987 · NHLBI · H. LEE MOFFITT CANCER CTR & RES INST · PI Joseph A Pidala · 2017 to 2026
$2.1M
BMT CTN Core - University of MinnesotaUG1HL069290 · NHLBI · UNIVERSITY OF MINNESOTA · PI Mark Juckett, Margaret L MacMillan · 2017 to 2026
$1.9M
Translational Research in Blood and Marrow TransplantationUG1HL069310 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI RICHARD J JONES · 2017 to 2026
$1.6M
Prognostic implications of mitochondrial inheritance in myelodysplastic syndromes after stem-cell transplantationK01HL164972 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Jing Dong · 2023 to 2026
$697k
NHLBI NIH HHS K01 HL164972NHLBI NIH HHS P01 HL158505NHLBI NIH HHS R01 HL095791NHLBI NIH HHS R01 HL181969NHLBI NIH HHS U10 HL069294NHLBI NIH HHS U24 HL138660NHLBI NIH HHS UG1 HL069290NHLBI NIH HHS UG1 HL069310NHLBI NIH HHS UG1 HL069315NHLBI NIH HHS UG1 HL108987
6 · The paper itself

Abstract

Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 (NCT03959241). We quantified T-cell immune reconstitution using multi-modal analysis, including T-cell receptor (TCR) sequencing of 2,359 longitudinal samples (180,432,350 T-cells). Compared to Tac/MTX, PT-Cy was associated with an early, substantial reduction in TCR diversity that was sustained for 2 years. PT-Cy led to a T-cell reconstitution bottleneck, including reduced thymic output and virus-associated TCRs. Decreased D+14 TCR diversity predicted prevention of chronic GVHD, but also correlated with increased moderate-to-severe infections. This study reveals how distinct immunosuppression strategies have significant effects on the global immune repertoire, underpinning post-transplant clinical outcomes.

Identifiers

PMID40061351
PMCPMC11888538

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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.