Evidence map›Paper›PMID 33449816›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2021

Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD.

Benjamin Watkins, Muna Qayed, Courtney McCracken, Brandi Bratrude, Kayla Betz, Yvonne Suessmuth, Alison Yu, Shauna Sinclair, Scott Furlan, Steven Bosinger and 36 more

Open access · greenAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed, 3 pooled it
24.9field-weighted citation impact, top 1% 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

152 citing papers in PubMed, 3 syntheses or guidelines pooled it, 237 citations in OpenAlex.

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  18. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
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92 more citing papers are in PubMed but not listed here.

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

46 authors at 20 institutions in 2 countries.

Benjamin WatkinsAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, and Emory University, Atlanta, GA.ORCID 0000-0002-6675-8071
Muna QayedAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, and Emory University, Atlanta, GA.ORCID 0000-0001-7689-343X
Courtney McCrackenEmory University, Atlanta, GA.
Brandi BratrudeBoston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA.ORCID 0000-0002-1498-1001
Kayla BetzBoston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA.
Yvonne SuessmuthAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, and Emory University, Atlanta, GA.
Alison YuBoston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA.
Shauna SinclairSeattle Children's Hospital, Seattle, WA.
Scott FurlanFred Hutchinson Cancer Research Center, Seattle, WA.ORCID 0000-0003-3007-9840
Steven BosingerEmory University, Yerkes National Primate Research Center, Atlanta, GA.
Victor TkachevBoston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA.ORCID 0000-0001-6011-0576
James RhodesAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
Audrey Grizzle TumlinAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
Alexandria NarayanFred Hutchinson Cancer Research Center, Seattle, WA.
Kayla CribbinSeattle Children's Hospital, Seattle, WA.
Scott GillespieEmory University, Atlanta, GA.
Ted A GooleyFred Hutchinson Cancer Research Center, Seattle, WA.
Marcelo C PasquiniCenter for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI.ORCID 0000-0003-1579-2293
Kyle HebertCenter for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI.
Urvi KapoorIcahn School of Medicine, New York City, NY.
Andre RogatkoCedars Sinai Medical Center, Los Angeles, CA.
Mourad TighiouartCedars Sinai Medical Center, Los Angeles, CA.
Sungjin KimCedars Sinai Medical Center, Los Angeles, CA.
Catherine BreseeCedars Sinai Medical Center, Los Angeles, CA.ORCID 0000-0002-5710-4906
Sung W ChoiUniversity of Michigan, Ann Arbor, MI.ORCID 0000-0002-6321-3834
Jeffrey DavisBC Children's Hospital, University of British Columbia, Vancouver, Canada.ORCID 0000-0002-5959-7345
Christine DuncanBoston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA.
Roger GillerCenter for Cancer and Blood Disorders, Children Hospital of Colorado, University of Colorado, Aurora, CO.ORCID 0000-0003-4588-7111
Michael GrimleyUniversity of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.ORCID 0000-0003-2056-5167
Andrew C HarrisUniversity of Utah, Primary Children's Hospital, Salt Lake City, UT.ORCID 0000-0002-4538-8817
David JacobsohnChildren's National Health System, Washington, DC.
Nahal LalefarUniversity of California San Francisco, UCSF Benioff Children's Hospital Oakland, Oakland, CA.
Maxim NorkinBaptist Medical Center Jacksonville, Jacksonville, FL.
Nosha FarhadfarUniversity of Florida, UF Health Shands Hospital, Gainesville, FL.
Michael A PulsipherChildren's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles, CA.ORCID 0000-0003-3030-8420
Shalini ShenoyWashington University School of Medicine, St Louis, MO.
Aleksandra PetrovicSeattle Children's Hospital, Seattle, WA.
Kirk R SchultzBC Children's Hospital, University of British Columbia, Vancouver, Canada.ORCID 0000-0002-0001-6438
Gregory A YanikUniversity of Michigan, Ann Arbor, MI.
Edmund K WallerWinship Cancer Institute, Emory University, Atlanta, GA.ORCID 0000-0003-0816-6729
John E LevineIcahn School of Medicine, New York City, NY.ORCID 0000-0002-5611-7828
James L FerraraIcahn School of Medicine, New York City, NY.ORCID 0000-0001-8595-3940
Bruce R BlazarUniversity of Minnesota, Department of Pediatrics, Division of Blood and Marrow Transplantation, Minneapolis, MN.ORCID 0000-0002-9608-9841
Amelia LangstonWinship Cancer Institute, Emory University, Atlanta, GA.ORCID 0000-0003-0649-1915
John T HoranBoston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA.
Leslie S KeanBoston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA.
Emory University · USBoston Children's Hospital · USCedars-Sinai Medical Center · USFred Hutch Cancer Center · USIcahn School of Medicine at Mount Sinai · USSeattle Children's Hospital · USAflac (United States) · USMedical College of Wisconsin · USUniversity of British Columbia · CAUniversity of Michigan · USBaptist Medical Center Jacksonville · USCenter for Cancer and Blood Disorders · USChildren's Hospital of Los Angeles · USChildren's National · USCincinnati Children's Hospital Medical Center · USPrimary Children's Hospital · USUF Health Shands Hospital · USUniversity of California, San Francisco · USUniversity of Minnesota · USWashington University in St. Louis · US

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI J SUNIL RAO · 1995 to 2026
$48.2M
TUMOR VACCINES AND BONE MARROW TRANSPLANTATIONP01CA039542 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PAVAN REDDY · 1985 to 2026
$47.9M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SHARPE, ARLENE H. · 2003 to 2023
$42.5M
Novel Biologic Therapies for GVHDR01HL095791 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI KEAN, LESLIE S · 2010 to 2025
$13.3M
Enhancing Treg Therapeutic Efficacy in GVHDR01HL118979 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, HIPPEN, KELI L · 2014 to 2025
$6.7M
Atlanta Pediatric Scholars ProgramK12HD072245 · NICHD · EMORY UNIVERSITY · PI Shari Barkin · 2012 to 2026
$5.5M
T-CELL TARGETING FOR GVHDR01HL056067 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1995 to 2022
$5.4M
In Vivo Prevention of Murine GVHDR37AI034495 · NIAID · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar · 2017 to 2026
$5.4M
Nongenotoxic conditioning for gene therapy and allogeneic transplantation in Fanconi anemiaR01HL147324 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Bruce R Blazar, HANS-PETER KIEM · 2020 to 2026
$4.1M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalKL2TR000455 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$2.9M
Exploiting the VISTA Pathway to Prevent Acute GVHD and Control Steroid Refractory DiseaseR01HL155114 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, NOELLE, RANDOLPH J. · 2021 to 2024
$2.7M
Phase 2 Study of Abatacept with Calcineurin Inhibition and Methotrexate for GVHDR01FD004099 · FDA · SEATTLE CHILDREN'S HOSPITAL · PI KEAN, LESLIE S · 2013 to 2016
$1.7M
FDA HHS R01 FD004099NCATS NIH HHS KL2 TR000455NCI NIH HHS P01 CA039542NCI NIH HHS P01 CA065493NHLBI NIH HHS K23 HL136900NHLBI NIH HHS R01 HL056067NHLBI NIH HHS R01 HL095791NHLBI NIH HHS R01 HL118979NHLBI NIH HHS R01 HL147324NHLBI NIH HHS R01 HL155114NHLBI NIH HHS UG1 HL069254NIAID NIH HHS P01 AI056299NIAID NIH HHS R37 AI034495NICHD NIH HHS K12 HD072245
6 · The paper itself

Abstract

purposeSevere (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD.

methodsABA2 enrolled adults and children with hematologic malignancies under two strata: a randomized, double-blind, placebo-controlled stratum (8/8-HLA-matched URD), comparing CNI/MTX plus abatacept with CNI/MTX plus placebo, and a single-arm stratum (7/8-HLA-mismatched URD) comparing CNI/MTX plus abatacept versus CNI/MTX CIBMTR controls. The primary end point was day +100 grade 3-4 AGVHD, with day +180 severe-AGVHD-free-survival (SGFS) a key secondary end point. Sample sizes were calculated using a higher type-1 error (0.2) as recommended for phase II trials, and were based on predicting that abatacept would reduce grade 3-4 AGVHD from 20% to 10% (8/8s) and 30% to 10% (7/8s). ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days).

resultsIn 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo) (

conclusionAdding abatacept to URD HCT was safe, reduced AGVHD, and improved SGFS. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.

Indexed as

AbataceptAdolescentAdultAgedChildCyclosporineGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansImmunosuppressive AgentsMaleMethotrexateMiddle AgedTacrolimusYoung AdultAbataceptCyclosporineImmunosuppressive AgentsMethotrexateTacrolimus

Identifiers

PMID33449816
PMCPMC8260909
OpenAlexW3120895755

What OpenQuestion holds

Textmetadata
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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.