Evidence map›Paper›PMID 22784116›Full record

Trial reportThe New England journal of medicine2012

Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease.

Ran Reshef, Selina M Luger, Elizabeth O Hexner, Alison W Loren, Noelle V Frey, Sunita D Nasta, Steven C Goldstein, Edward A Stadtmauer, Jacqueline Smith, Sarah Bailey and 6 more

2 registry-linked trialsAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in The New England journal of medicine, 2012. 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, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 2 pooled it
–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.

NCT00948753 phase1 / phase2completednot on this map

Safety and Efficacy of Maraviroc, a CCR5-inhibitor in Prophylaxis of Graft-Versus-Host Disease in Patients Undergoing Non-Myeloablative Allogeneic Stem-Cell Transplantation

TypeinterventionalSponsorAbramson Cancer Center at Penn MedicineRan2009 to 2011Enrolled38ConditionsGraft-versus-host Disease, Hematopoietic Stem Cell TransplantationArmsMaraviroc 150 MG, Maraviroc 300 mg, Maraviroc 300 mg Phase II
NCT02338232 naterminatednot on this mapstarted 2015, after this paper: background citation

Pilot Study of Telmisartan (Micardis) For the Prevention of Acute Graft vs. Host Disease Post Allogeneic Hematopoietic Stem Cell Transplantation

TypeinterventionalSponsorHackensack Meridian HealthRan2015 to 2023Enrolled32ConditionsGVHDArmsTelmisartan
3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  6. Extended CCR5 Blockade for Graft-versus-Host Disease Prophylaxis Improves Outcomes of Reduced-Intensity Unrelated Donor Hematopoietic Cell Transplantation: A Phase II Clinical Trial.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019
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  8. Pharmacodynamic Monitoring Predicts Outcomes of CCR5 Blockade as Graft-versus-Host Disease Prophylaxis.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018
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  9. Ex Vivo CD34Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017
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  18. Sibling donor and recipient immune modulation with atorvastatin for the prophylaxis of acute graft-versus-host disease.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013
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  20. Review

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

16 authors.

Ran ReshefAbramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ran.reshef@uphs.upenn.edu
Selina M Luger
Elizabeth O Hexner
Alison W Loren
Noelle V Frey
Sunita D Nasta
Steven C Goldstein
Edward A Stadtmauer
Jacqueline Smith
Sarah Bailey
Rosemarie Mick
Daniel F Heitjan
Stephen G Emerson
James A Hoxie
Robert H Vonderheide
David L Porter

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
Bone Marrow Transplant Clinical NetworkU01HL069286 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI STADTMAUER, EDWARD A · 2001 to 2010
$2.1M
BMT CTN Core- University of Pennsylvania Abramson Cancer CenterUG1HL069286 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Edward A Stadtmauer · 2017 to 2026
$2.0M
Bone Marrow Transplant Clinical NetworkU10HL069286 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI STADTMAUER, EDWARD A · 2011 to 2016
$986k
Mid-career investigator award in allogeneic adoptive immunotherapyK24CA117879 · NCI · UNIVERSITY OF PENNSYLVANIA · PI PORTER, DAVID L · 2006 to 2010
$778k
NCI NIH HHS K24 CA117879NCI NIH HHS K24-CA117879NCI NIH HHS P30 CA016520NCI NIH HHS P30-CA16520NHLBI NIH HHS U01 HL069286NHLBI NIH HHS U01-HL069286NHLBI NIH HHS U10 HL069286NHLBI NIH HHS UG1 HL069286
6 · The paper itself

Abstract

backgroundGraft-versus-host disease (GVHD) is a major barrier to successful allogeneic hematopoietic stem-cell transplantation (HSCT). The chemokine receptor CCR5 appears to play a role in alloreactivity. We tested whether CCR5 blockade would be safe and limit GVHD in humans.

methodsWe tested the in vitro effect of the CCR5 antagonist maraviroc on lymphocyte function and chemotaxis. We then enrolled 38 high-risk patients in a single-group phase 1 and 2 study of reduced-intensity allogeneic HSCT that combined maraviroc with standard GVHD prophylaxis.

resultsMaraviroc inhibited CCR5 internalization and lymphocyte chemotaxis in vitro without impairing T-cell function or formation of hematopoietic-cell colonies. In 35 patients who could be evaluated, the cumulative incidence rate (±SE) of grade II to IV acute GVHD was low at 14.7±6.2% on day 100 and 23.6±7.4% on day 180. Acute liver and gut GVHD were not observed before day 100 and remained uncommon before day 180, resulting in a low cumulative incidence of grade III or IV GVHD on day 180 (5.9±4.1%). The 1-year rate of death that was not preceded by disease relapse was 11.7±5.6% without excessive rates of relapse or infection. Serum from patients receiving maraviroc prevented CCR5 internalization by CCL5 and blocked T-cell chemotaxis in vitro, providing evidence of antichemotactic activity.

conclusionsIn this study, inhibition of lymphocyte trafficking was a specific and potentially effective new strategy to prevent visceral acute GVHD. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00948753.).

Indexed as

CCR5 Receptor AntagonistsAdultAgedChemokine CCL3Chemokine CCL5Chemotaxis, LeukocyteCyclohexanesFemaleGraft vs Host DiseaseHematologic NeoplasmsHematopoietic Stem Cell TransplantationHumansKaplan-Meier EstimateMaleMaravirocMiddle AgedCCR5 Receptor AntagonistsChemokine CCL3Chemokine CCL5CyclohexanesMaravirocTriazoles

Identifiers

PMID22784116
PMCPMC3568501

What OpenQuestion holds

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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.