Korean J Hematol.  2011 Sep;46(3):153-163. 10.5045/kjh.2011.46.3.153.

Treatment of chronic graft-versus-host disease: Past, present and future

• Martin PJ
• Inamoto Y
• Carpenter
• Lee SJ
• Flowers ME

• KMID: 2251997
• DOI: http://doi.org/10.5045/kjh.2011.46.3.153

Abstract

Chronic GVHD was recognized as a complication of allogeneic hematopoietic cell transplantation more than 30 years ago, but progress has been slowed by the limited insight into the pathogenesis of the disease and the mechanisms that lead to development of immunological tolerance. Only 6 randomized phase III treatment studies have been reported. Results of retrospective studies and prospective phase II clinical trials suggested overall benefit from treatment with mycophenolate mofetil or thalidomide, but these results were not substantiated by phase III studies of initial systemic treatment for chronic GVHD. A comprehensive review of published reports showed numerous deficiencies in studies of secondary treatment for chronic GVHD. Fewer than 10% of reports documented an effort to minimize patient selection bias, used a consistent treatment regimen, or tested a formal statistical hypothesis that was based on a contemporaneous or historical benchmark. In order to enable valid comparison of the results from different studies, eligibility criteria, definitions of individual organ and overall response, and time of assessment should be standardized. Improved treatments are more likely to emerge if reviewers and journal editors hold authors to higher standards in evaluating manuscripts for publication.

Keyword

Chronic graft-versus-host disease; Treatment; Phase II clinical trials; Review

MeSH Terms

Bias (Epidemiology)
Cell Transplantation
Mycophenolic Acid
Patient Selection
Publications
Thalidomide
Transplants
Mycophenolic Acid
Thalidomide

Figure

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  Fig. 1 Treatments evaluated in prior reports. Treatments are listed in order of frequency among the 60 reports included in the literature review.

• 

  Fig. 2 Distribution of scores representing the total number of criteria met by each report for the 60 studies included in the literature review.

• 

  Fig. 3 Historical outcomes after secondary systemic therapy for chronic GVHD. The upper solid curve shows time to treatment failure defined as a qualitative change in systemic therapy or death during secondary therapy. The dashed curve shows time to treatment failure or recurrent malignancy during secondary therapy. The lower solid curve shows the cumulative incidence of discontinued systemic treatment after resolution of chronic GVHD. The dot on the dashed line indicates that approximately 40% of patients were alive at 1 year after the onset of secondary treatment without a qualitative change in systemic therapy and without recurrent malignancy. Chronic GVHD was defined according to historical criteria and might not reflect results to be expected for patients with chronic GVHD defined according to NIH criteria. The figure is adapted from reference [29]. a)During secondary therapy.

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