Evidence map›Paper›PMID 24295572›Full record

Trial reportThe Lancet. Oncology2014

Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial.

Sung Won Choi, Thomas Braun, Lawrence Chang, James L M Ferrara, Attaphol Pawarode, John M Magenau, Guoqing Hou, Jan H Beumer, John E Levine, Steve Goldstein and 13 more

2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 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 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
8.2field-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.

NCT00810602 phase1 / phase2completednot on this map

Phase II Trial of Vorinostat Plus Tacrolimus & Mycophenolate to Prevent Graft Versus Host Disease Following Reduced Intensity Conditioning Related Donor Allogeneic Transplant

TypeinterventionalSponsorPavan Reddy, MDRan2009 to 2013Enrolled61ConditionsHematologic Malignancies, Graft vs Host DiseaseArmsreduced intensity, related donor stem cell transplant, tacrolimus (standard GVHD prophylaxis), mycophenolate (standard GVHD prophylaxis), vorinostat
NCT03167437 phase1 / phase2recruitingnot on this mapstarted 2017, after this paper: background citation

An Open-Label, Proof of Concept Study of Vorinostat for the Treatment of Moderate-to-Severe Crohn's Disease, Ulcerative Colitis, and Chronic Granulomatous Disease Colitis Patients and Maintenance Therapy With Ustekinumab

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2017 to 2035Enrolled35ConditionsCrohn's DiseaseArmsVorinostat, Ustekinumab
3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 130 citations in OpenAlex.

  1. Trial
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  3. Cognitive Function and Quality of Life in Vorinostat-Treated Patients after Matched Unrelated Donor Myeloablative Conditioning Hematopoietic Cell Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019
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  7. Combination Therapy for Graft-versus-Host Disease Prophylaxis with Etanercept and Extracorporeal Photopheresis: Results of a Phase II Clinical Trial.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2016
    Trial
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  9. Review
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  14. Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  15. Observational
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  17. Article
  18. Article
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 3 countries.

Sung Won ChoiBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Thomas BraunDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Lawrence ChangBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
James L M FerraraBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Attaphol PawarodeBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
John M MagenauBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Guoqing HouBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Jan H BeumerPharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
John E LevineBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Steve GoldsteinBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Daniel R CourielBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Keith Stockerl-GoldsteinBlood and Marrow Transplantation Program, Washington University, St Louis, MO, USA.
Oleg I KrijanovskiSutter East Bay Medical Foundation, Berkeley, CA, USA.
Carrie KitkoBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Gregory A YanikBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Michael H LehmannDepartment of Cardiology, University of Michigan, Ann Arbor, MI, USA.
Isao TawaraHematology-Oncology, Mie University Hospital, Mie, Japan.
Yaping SunBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
Sophie PaczesnyPediatric Hematology Oncology, Indiana University, Indianapolis, IN, USA.
Markus Y MaparaBlood and Marrow Transplantation Program, Columbia University, New York, NY, USA.
Charles A DinarelloDepartment of Medicine, University of Colorado, Aurora, CO, USA; Department of Medicine, University Medical Center Nijmegen, Netherlands.
John F DiPersioDepartment of Cardiology, University of Michigan, Ann Arbor, MI, USA.
Pavan ReddyBlood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA. Electronic address: reddypr@umich.edu.
University of Michigan–Ann Arbor · USColumbia University · USIndiana University – Purdue University Indianapolis · USMie University Hospital · JPRadboud University Nijmegen · NLUniversity of Pittsburgh · USWashington University in St. Louis · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
TUMOR VACCINES AND BONE MARROW TRANSPLANTATIONP01CA039542 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JAMES L. M. FERRARA · 1985 to 2026
$47.9M
Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
Targeting antigen presentation to enhance GVL responses after Bone Marrow TransplR01HL090775 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI REDDY, PAVAN · 2008 to 2016
$3.4M
Development of a Novel Strategy to Prevent Experimental GVHDR01CA143379 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI REDDY, PAVAN · 2010 to 2014
$739k
Phase II Trial of Vorinostat plus Tacrolimus and Mycophenolate to Prevent GVHDK23AI091623 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHOI, SUNG WON · 2011 to 2015
$658k
NCATS NIH HHS UL1 TR000043NCI NIH HHS P01 CA039542NCI NIH HHS P01CA039542NCI NIH HHS P30 CA047904NCI NIH HHS P30CA047904NCI NIH HHS R01 CA143379NCI NIH HHS R01CA143379NHLBI NIH HHS R01 HL090775NIAID NIH HHS 1K23AI091623NIAID NIH HHS K23 AI091623NIAID NIH HHS R01 AI015614NIAID NIH HHS R01AI15614
6 · The paper itself

Abstract

backgroundAcute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and activity of vorinostat, in combination with standard immunoprophylaxis, for prevention of GVHD in patients undergoing related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation.

methodsBetween March 31, 2009, and Feb 8, 2013, we did a prospective, single-arm, phase 1/2 study at two centres in the USA. We recruited adults (aged ≥18 years) with high-risk haematological malignant diseases who were candidates for reduced-intensity conditioning haemopoietic stem-cell transplantation and had an available 8/8 or 7/8 HLA-matched related donor. All patients received a conditioning regimen of fludarabine (40 mg/m(2) daily for 4 days) and busulfan (3.2 mg/kg daily for 2 days) and GVHD immunoprophylaxis of mycophenolate mofetil (1 g three times a day, days 0-28) and tacrolimus (0.03 mg/kg a day, titrated to a goal level of 8-12 ng/mL, starting day -3 until day 180). Vorinostat (either 100 mg or 200 mg, twice a day) was initiated 10 days before haemopoietic stem-cell transplantation until day 100. The primary endpoint was the cumulative incidence of grade 2-4 acute GVHD by day 100. This trial is registered with ClinicalTrials.gov, number NCT00810602.

findings50 patients were assessable for both toxic effects and response; eight additional patients were included in the analysis of toxic effects. All patients engrafted neutrophils and platelets at expected times after haemopoietic stem-cell transplantation. The cumulative incidence of grade 2-4 acute GVHD by day 100 was 22% (95% CI 13-36). The most common non-haematological adverse events included electrolyte disturbances (n=15), hyperglycaemia (11), infections (six), mucositis (four), and increased activity of liver enzymes (three). Non-symptomatic thrombocytopenia after engraftment was the most common haematological grade 3-4 adverse event (nine) but was transient and all cases resolved swiftly.

interpretationAdministration of vorinostat in combination with standard GVHD prophylaxis after related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation is safe and is associated with a lower than expected incidence of severe acute GVHD. Future studies are needed to assess the effect of vorinostat for prevention of GVHD in broader settings of haemopoietic stem-cell transplantation.

fundingMerck, Leukemia and Lymphoma Society, National Institutes of Health, St Baldrick's Foundation, Michigan Institute for Clinical and Health Research.

Indexed as

Hematopoietic Stem Cell TransplantationTransplantation ConditioningAcute DiseaseAdultAgedFemaleGraft vs Host DiseaseHistone Deacetylase InhibitorsHumansHydroxamic AcidsImmunosuppressive AgentsMaleMiddle AgedMycophenolic AcidProspective StudiesTacrolimusHistone Deacetylase InhibitorsHydroxamic AcidsImmunosuppressive AgentsMycophenolic AcidTacrolimusVorinostat

Identifiers

PMID24295572
PMCPMC4103793
OpenAlexW2153643980

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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.