Evidence map›Paper›PMID 25139358›Full record

ArticleBlood2014

Donor CD4+ Foxp3+ regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice.

Sudipto Ganguly, Duncan B Ross, Angela Panoskaltsis-Mortari, Christopher G Kanakry, Bruce R Blazar, Robert B Levy, Leo Luznik

2 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 135 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 2% of its field
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.

NCT03240731 phase2completednot on this mapstarted 2017, after this paper: background citation

Bone Marrow Transplantation HLA Haploidentical After a Reduced Intensity Conditioning and Prevention of GvHD Based on Post-transplant Cyclophosphamide Administration in Patients With Severe Sickle Cell Disease

TypeinterventionalSponsorCentre Hospitalier Intercommunal CreteilRan2017 to 2024Enrolled25ConditionsSickle Cell DiseaseArmsbone marrow transplant
NCT06845592 narecruitingnot on this mapstarted 2025, after this paper: background citation

SHARP - Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia

TypeinterventionalSponsorUniversity Of PerugiaRan2025 to 2031Enrolled51ConditionsAcute Myeloid Leukaemia (AML), Acute Lymphoblastic Leukemia ALL, High Risk Leukaemia, Leukaemia RelapseArmstotal marrow/lymphoid irradiation
3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.

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75 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Sudipto GangulyDivision of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD;
Duncan B RossDepartment of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL; and.
Angela Panoskaltsis-MortariDivision of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN.
Christopher G KanakryDivision of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD;
Bruce R BlazarDivision of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN.
Robert B LevyDepartment of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL; and.
Leo LuznikDivision of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD;
Sidney Kimmel Comprehensive Cancer Center · USMasonic Cancer CenterUniversity of Miami · US

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SHARPE, ARLENE H. · 2003 to 2023
$42.5M
Project 3: Humoral Targets and B Cell Biology in Chronic Graft-vs.-Host DiseaseP01CA142106 · NCI · DANA-FARBER CANCER INST · PI CUTLER, COREY S · 2009 to 2019
$17.5M
Enhancing Treg Therapeutic Efficacy in GVHDR01HL118979 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, HIPPEN, KELI L · 2014 to 2025
$6.7M
TRAINING PROGRAM IN HEMATOLOGYT32HL007525 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI ROBERT A BRODSKY · 1985 to 2026
$6.2M
IN VIVO PREVENTION OF MURINE GVHDR01AI034495 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1993 to 2016
$6.2M
T-CELL TARGETING FOR GVHDR01HL056067 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1995 to 2022
$5.4M
GVL TO REDUCE AML RELAPSE AFTER MURINE ALLOGENEIC BMTR01CA072669 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1997 to 2017
$4.9M
ALLOGENEIC MIHA INDUCED MARROW ALLOGRAFT RESISTANCER01AI046689 · NIAID · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LEVY, ROBERT BENJAMIN · 2001 to 2010
$3.5M
MECHANISMS OF GVHD PREVENTION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDER01HL110907 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI LUZNIK, LEO, WARREN, EDUS HOUSTON · 2012 to 2015
$1.7M
Augmenting Antitumor Immunity after AllograftingR01CA122779 · NCI · JOHNS HOPKINS UNIVERSITY · PI LUZNIK, LEO · 2008 to 2012
$1.5M
NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA142106NCI NIH HHS R01 CA072669NCI NIH HHS R01 CA122779NCI NIH HHS R01CA122779NHLBI NIH HHS R01 HL056067NHLBI NIH HHS R01 HL110907NHLBI NIH HHS R01HL110907NHLBI NIH HHS R01 HL118979NHLBI NIH HHS R01HL56067NHLBI NIH HHS T32 HL007525NIAID NIH HHS P01 AI056299NIAID NIH HHS R01 AI034495NIAID NIH HHS R01 AI046689NIAID NIH HHS R01AI34495NIAID NIH HHS R01AI46689
6 · The paper itself

Abstract

Posttransplantation cyclophosphamide (PTCy) is an effective prophylaxis against graft-versus-host disease (GVHD). However, it is unknown whether PTCy works singularly by eliminating alloreactive T cells via DNA alkylation or also by restoring the conventional (Tcon)/regulatory (Treg) T-cell balance. We studied the role of Tregs in PTCy-mediated GVHD prophylaxis in murine models of allogeneic blood or marrow transplantation (alloBMT). In 2 distinct MHC-matched alloBMT models, infusing Treg-depleted allografts abrogated the GVHD-prophylactic activity of PTCy. Using allografts in which Foxp3(+) Tregs could be selectively depleted in vivo, either pre- or post-PTCy ablation of donor thymus-derived Tregs (tTregs) abolished PTCy protection against GVHD. PTCy treatment was associated with relative preservation of donor Tregs. Experiments using combinations of Foxp3(-) Tcons and Foxp3(+) Tregs sorted from different Foxp3 reporter mice indicated that donor Treg persistence after PTCy treatment was predominantly caused by survival of functional tTregs that retained Treg-specific demethylation and also induction of peripherally derived Tregs. Finally, adoptive transfer of tTregs retrieved from PTCy-treated chimeras rescued PTCy-treated, Treg-depleted recipients from lethal GVHD. Our findings indicate that PTCy-mediated protection against GVHD is not singularly dependent on depletion of donor alloreactive T cells but also requires rapidly recovering donor Tregs to initiate and maintain alloimmune regulation.

Indexed as

ChemopreventionAnimalsBone Marrow TransplantationCyclophosphamideDisease Models, AnimalDNA MethylationForkhead Transcription FactorsGraft vs Host DiseaseLymphoid TissueMiceTissue DonorsT-Lymphocytes, RegulatoryTransplantation ChimeraTransplantation, HomologousCyclophosphamideForkhead Transcription FactorsFoxp3 protein, mouse

Identifiers

PMID25139358
PMCPMC4186542
OpenAlexW2126724696

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.