Steroids Versus Steroids Plus Additional Agent in Frontline Treatment of Acute Graft-versus-Host Disease: A Systematic Review and Meta-Analysis of Randomized Trials

Armin Rashidi, John F. DiPersio, Brenda M. Sandmaier, Graham A. Colditz, Daniel J. Weisdorf

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Despite extensive research in the last few decades, progress in treatment of acute graft-versus-host disease (aGVHD), a common complication of allogeneic hematopoietic cell transplantation (HCT), has been limited and steroids continue to be the standard frontline treatment. Randomized clinical trials (RCTs) have failed to find a beneficial effect of escalating immunosuppression using additional agents. Considering the small number of RCTs, limited sample sizes, and frequent early termination because of anticipated futility, we conducted a systematic review and an aggregate data meta-analysis to explore whether a true efficacy signal has been missed because of the limitations of individual RCTs. Seven reports met our inclusion criteria. The control arm in all studies was 2 mg/kg/day prednisone (or equivalent). The additional agent(s) used in the experimental arm(s) were higher-dose steroids, antithymocyte globulin, infliximab, anti-interleukin-2 receptor antibody (daclizumab and BT563), CD5-specific immunotoxin, and mycophenolate mofetil. Random effects meta-analysis revealed no efficacy signal in pooled response rates at various times points. Overall survival at 100 days was significantly worse in the experimental arm (relative risk [RR], .83; 95% confidence interval [CI], .74 to .94; P = .004, data from 3 studies) and showed a similar trend (albeit not statistically significantly) at 1 year as well (RR, .86; 95% CI, .68 to 1.09; P = .21, data from 5 studies). In conclusion, these results argue against the value of augmented generic immunosuppression beyond steroids for frontline treatment of aGVHD and emphasize the importance of developing alternative strategies. Novel forms of immunomodulation and targeted therapies against non-immune-related pathways may enhance the efficacy of steroids in this setting, and early predictive and prognostic biomarkers can help identify the subgroup of patients who would likely need treatments other than (or in addition to) generic immunosuppression.

Original languageEnglish (US)
Pages (from-to)1133-1137
Number of pages5
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2016

Bibliographical note

Funding Information:
Financial disclosure statement: A.R. was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences. Support for this study was provided by grant U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute , and University of Minnesota Cancer Center Support Grant P30CA077598 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank investigators at the University of Minnesota Blood and Marrow Transplant Program and the Blood and Marrow Clinical Trials Network for inclusion of additional data, not included in the originally published manuscripts.

Publisher Copyright:
© 2016 The American Society for Blood and Marrow Transplantation.

Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.

Keywords

  • Graft-versus-host disease
  • Meta-analysis
  • Randomized clinical trial
  • Steroids

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