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Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?

Bone Marrow Transplantation volume 48, pages 203–209 (2013)Cite this article

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Abstract

Chronic GVHD (cGVHD) is an important problem after allotransplants. Some risk factors for cGVHD are similar to those of acute GVHD (aGVHD) but others are distinct indicating sometimes overlapping but unique pathogeneses. Precise incidence and prevalence data of cGVHD are lacking because of diverse diagnostic criteria but a 50% risk is a reasonable estimate. Incidence and prevalence of cGVHD are probably growing because of increased use of unrelated donors, blood rather than bone marrow (BM) grafts, decreased early transplant-related mortality (TRM) and increasing frequency of allotransplants. Pathophysiology of cGVHD is complex and poorly understood. Notably, no reliable surrogate end point to predict mechanism(s) of cGVHD has been identified. Therapy of cGVHD is unsatisfactory. Corticosteroids are effective but other drugs are controversial and few are rigorously tested in randomized trials. Highly variable response rates are reported because of small sample sizes and inconsistencies in eligibility, diagnostic and response criteria. We focus on the possible role of immunomodulatory drugs (IMiDs), thalidomide lenalidomide and pomalidomide, in preventing and treating cGVHD. The data suggest activity of thalidomide but at doses not clinically practical in many instances. There are few data with lenalidomide. Trials of pomalidomide, which has immune activities like thalidomide but with fewer adverse effects, are beginning. Because cGVHD is not recently reviewed in Bone Marrow Transplantation, we give a brief background and discuss challenges in diagnosing, understanding and treating cGVHD including the recently proposed National Institutes of Health consensus criteria for cGVHD.

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Acknowledgements

RPG acknowledges support from the NIHR Biomedical Research Centre funding scheme. Statements included in this article do not represent the official position of the NCI, NIH or the US government. SZP receives partial research funding support through the Cooperative Research and Development Agreement for intramural-PHS clinical research executed between the NCI and Celgene (CRADA #02328). Our many collaborators over several decades, especially who criticized us and making us better scientists and clinicians and this a better typescript. Special thanks to Iskra Pusic (Washington Univerity, St Louis, MO) and Lana Grkovic (Rebro University Hospital, Zagreb, Croatia) for their input to an earlier review section of this typescript. Hillard M Lazarus (Case Western Reserve University, Celevland, OH) suggested a review of cGVHD and IMiDs and provided many helpful comments.

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  1. Department of Medicine, Division of Hematology/Medical Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Y P L Linhares

  2. GVHD and Autoimmunity Unit, Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD, USA

    S Pavletic

  3. Department of Medicine, Division of Experimental Medicine, Section of Haematology, Imperial College, London, UK

    R P Gale

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SZP is an employee of the Center for Cancer Research, National Cancer Institute and National Institutes of Health. RPG is a parttime employee of Celgene Corp.

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Linhares, Y., Pavletic, S. & Gale, R. Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?. Bone Marrow Transplant 48, 203–209 (2013). https://doi.org/10.1038/bmt.2012.76

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