Evidence map›Paper›PMID 29061535›Full record

Trial reportBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation2018

Pharmacodynamic Monitoring Predicts Outcomes of CCR5 Blockade as Graft-versus-Host Disease Prophylaxis.

Austin P Huffman, Lee P Richman, Lisa Crisalli, Alex Ganetsky, David L Porter, Robert H Vonderheide, Ran Reshef

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 21% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. 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
    Trial
  3. Review
  4. Article
  5. Article
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

7 authors at 3 institutions in 1 country.

Austin P HuffmanAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Hematology/Oncology and the Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, New York.
Lee P RichmanAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania.
Lisa CrisalliAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Alex GanetskyAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
David L PorterAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Robert H VonderheideAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania.
Ran ReshefAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Hematology/Oncology and the Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, New York. Electronic address: ran.reshef@columbia.edu.
University of Pennsylvania · USCancer Research Institute · USColumbia University Irving Medical Center · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Bone Marrow Transplant Clinical NetworkU01HL069286 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI STADTMAUER, EDWARD A · 2001 to 2010
$2.1M
Lymphocyte trafficking blockade in allogeneic stem-cell transplantationK23CA178202 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RESHEF, RAN · 2013 to 2015
$520k
NCI NIH HHS K23 CA178202NCI NIH HHS P30 CA016520NHLBI NIH HHS U01 HL069286
6 · The paper itself

Abstract

Blocking lymphocyte trafficking after allogeneic hematopoietic stem cell transplantation is a promising strategy to prevent graft-versus-host disease (GVHD) while preserving the graft-versus-tumor response. Maraviroc, a CCR5 antagonist, has shown promise in clinical trials, presumably by disrupting the migration of effector cells to GVHD target organs. We describe a phosphoflow assay to quantify CCR5 blockade during treatment with maraviroc and used it to evaluate 28 patients in a phase II study. We found that insufficient blockade of CCR5 was associated with significantly worse overall survival (HR, 10.6; 95% CI, 2.2 to 52.0; P = .004) and higher rates of nonrelapse mortality (HR, 146; 95% CI, 1.0 to 20,600; P = .04) and severe acute GVHD (HR, 12; 95% CI, 1.9 to 76.6; P = .009). In addition, we found that pretransplant high surface expression of CCR5 on recipient T cells predicted higher nonrelapse mortality and worse GVHD- and relapse-free survival. Our results demonstrate that pharmacodynamic monitoring of CCR5 blockade unravels interpatient variability in the response to therapy and may serve as a clinically informative biomarker.

Indexed as

CCR5 Receptor AntagonistsGraft vs Host DiseaseMaravirocReceptors, CCR5AgedDisease-Free SurvivalFemaleHumansMaleMiddle AgedSurvival RateCCR5 protein, humanCCR5 Receptor AntagonistsMaravirocReceptors, CCR5Chemokine receptor blockadeGVHDMaraviroc

Identifiers

PMID29061535
PMCPMC5826857
OpenAlexW2765736682

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.