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Graft-Versus-Host Disease

Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation

Bone Marrow Transplantation volume 47, pages 581–588 (2012)Cite this article

Abstract

We investigated sirolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis in patients with advanced hematological malignancies receiving myeloablative hematopoietic cell transplantation (HCT) from HLA-identical sibling donors. On the basis of pre-study stopping rules, the trial was closed to accrual after enrollment of 11 adult patients. In all, 7 of the 11 patients received BU-containing preparative regimens. Sirolimus was discontinued in three patients because of the toxicity-related events of severe sinusoidal obstructive syndrome, portal vein thrombosis, altered mental status and in one patient because of the risk of poor wound healing. In all, 6 of the 11 patients developed grade II–IV acute GVHD (AGVHD) a median of 15.5 days post HCT. Two of three patients with grade IV AGVHD had sirolimus discontinued by 9 days post HCT. All patients responded to AGVHD therapy without GVHD-related deaths. There were two non-relapse- and two relapse-related deaths. At a median follow-up of 38 months (2–47 months), 7 of 11 patients were alive without disease. MMF and sirolimus GVHD prophylaxis did not reduce the risk of AGVHD, however, there were no GVHD-related deaths. The severe toxicities in the patients receiving the BU-containing preparative regimens limited the continued use of sirolimus and MMF for the prevention of AGVHD.

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Acknowledgements

This study was supported by the NIH Program Project Grant P01CA49605; Grant from the Doris Duke Charitable Foundation.

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Authors and Affiliations

  1. Department of Medicine, Stanford University, Stanford, CA, USA

    L Johnston, M Florek, S Arai, J Brown, G Laport, R Lowsky, D Miklos, J Shizuru & R Negrin

  2. Hospital and Clinics, Stanford University Medical Center, Stanford, CA, USA

    R Armstrong & K Sheehan

  3. Department of Pharmacy, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    J S McCune

  4. Department of Health Research and Policy, Stanford University, Stanford, CA, USA

    P Lavori

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  1. L Johnston
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  2. M Florek
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Correspondence to L Johnston.

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Johnston, L., Florek, M., Armstrong, R. et al. Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation. Bone Marrow Transplant 47, 581–588 (2012). https://doi.org/10.1038/bmt.2011.104

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