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Graft-Versus-Host Disease

Sirolimus for treatment of steroid-refractory acute graft-versus-host disease

Bone Marrow Transplantation volume 45, pages 1347–1351 (2010)Cite this article

Abstract

Acute GVHD (aGVHD) is a major cause of morbidity and mortality in hematopoietic allograft recipients. The best therapy for patients failing to respond, or not tolerating, systemic glucocorticoids remains undefined. We evaluated the efficacy of sirolimus in 34 patients, median age of 49 (23–67) years, with steroid-refractory (n=31) or steroid-intolerant (n=3) aGVHD. aGVHD was diagnosed at a median of 34 (7–1042) days post allografting, and confirmed by biopsy in all cases. Initial aGVHD treatment consisted of prednisone up to 2 mg/kg. Sirolimus was initiated at a median of 9 (1–255) days after glucocorticoid initiation. A sirolimus loading dose was administered to 19 (56%) of 34 patients, median 6 (3–8) mg, followed by maintenance of 1–2 mg/day to target therapeutic trough levels between 4 and 12 ng/ml. Overall response rate was 76%. Fifteen (44%) of 34 patients achieved CR, defined as complete resolution of aGVHD sustained for at least 1 month, after sirolimus initiation without additional immunosuppressive agents. CR was achieved in 11 (42%) of 31 steroid-refractory and 2 (67%) of 3 steroid-intolerant patients. Median OS after initiation of sirolimus was 5.6 months, and 1-year OS was 44% (95% CI: 27–60%). Sirolimus is effective in controlling steroid-refractory aGVHD.

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Author notes

  1. D Hoda and J Pidala: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    D Hoda, J Pidala, N Salgado-Vila, J Perkins, R Bookout, T Field, L Perez, E Ayala, J L Ochoa-Bayona, J Raychaudhuri, M Alsina, J Greene, W Janssen, H F Fernandez, C Anasetti & M A Kharfan-Dabaja

  2. Hematology–Oncology Fellowship Program, University of South Florida College of Medicine, Tampa, FL, USA

    D Hoda & J Pidala

  3. Department of Oncological Sciences, University of South Florida, Tampa, FL, USA

    J Kim, J Perkins, T Field, L Perez, E Ayala, J L Ochoa-Bayona, J Raychaudhuri, M Alsina, J Greene, H F Fernandez, C Anasetti & M A Kharfan-Dabaja

  4. Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    J Kim

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  1. D Hoda
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Correspondence to M A Kharfan-Dabaja.

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Hoda, D., Pidala, J., Salgado-Vila, N. et al. Sirolimus for treatment of steroid-refractory acute graft-versus-host disease. Bone Marrow Transplant 45, 1347–1351 (2010). https://doi.org/10.1038/bmt.2009.343

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