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14 - Graft-versus-host disease prophylactic regimens

Published online by Cambridge University Press:  05 November 2013

Joseph H. Antin
Affiliation:
Dana-Farber Cancer Institute, Boston
Deborah Yolin Raley
Affiliation:
Dana-Farber Cancer Institute, Boston
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Summary

Effective prophylaxis islimited by an incomplete understanding of the pathophysiology of thedisease. Drugs are often used in combination in an attempt to block severalpathways thought to cause graft-versus-host disease (GVHD). Use ofcalcineurin inhibitors in conjunction with methotrexate is the most commoncombination regimen. Institutions use a variety of combinations. The doseand toxicity of each agent are listed individually below.

  • Tacrolimus/methotrexate (MTX) or cyclosporine/MTX is superior to single-agent prophylaxis. When calcineurin inhibitors are used with lower doses of MTX, so-called “mini methotrexate” may attenuate mucositis caused by MTX.

  • Tacrolimus/mycophenolate mofetil (MMF) or cyclosporine/MMF are alternatives for patients who are unable to take MTX.

  • Sirolimus/tacrolimus/MTX or sirolimus/tacrolimus may allow for lower doses or the elimination of MTX, although there is an increased risk of veno-occlusive disease (VOD) if myeloablative conditioning is used.

  • Agents used for prophylaxis

    Methotrexate

    Mechanism of action

    Blocks the enzymedihydrofolate reductase, which inhibits the conversion of folic acid totetrahydrofolic acid, resulting in inhibition of the key precursors of DNA,RNA, and cellular protein.

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    Publisher: Cambridge University Press
    Print publication year: 2013

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    References

    Nevill, TJ, Tirgan, MH, Deeg, HJ, et al. Influence of post-methotrexate folinic acid rescue on regimen-related toxicity and graft-versus-host disease after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1992; 9: 349–54.Google ScholarPubMed

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