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Blood. 2008 Dec 1;112(12):4425-31. doi: 10.1182/blood-2008-07-169342. Epub 2008 Sep 5.

Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation.

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1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. corey_cutler@dfci.harvard.edu

Abstract

Sirolimus is an effective agent used in graft-versus-host disease (GVHD) prophylaxis after allogeneic transplantation. It also has antiproliferative effects on vascular endothelium when used to coat coronary artery stents. We noted an excess of veno-occlusive disease (VOD) in a clinical trial, and retrospectively reviewed the records of 488 patients to determine the association between sirolimus and VOD. When used with cyclophosphamide/total body irradiation (Cy/TBI) conditioning, sirolimus is associated with an increased incidence of VOD (OR 2.35, P = .005). The concomitant use of methotrexate further increased this rate (OR 3.23, P < .001), while sirolimus without methotrexate was not associated with an increased risk of VOD (OR 1.55, P = .33). Mortality after VOD diagnosis was unaffected, and overall treatment-related mortality was lowest when sirolimus was used without methotrexate. Similar findings were noted in matched, related, and unrelated as well as mismatched donor subgroups. When used with busulfan-based conditioning, sirolimus use was associated with an even higher rate of VOD (OR 8.8, P = .008). Our findings suggest that sirolimus use is associated with VOD after TBI-based transplantation when used with methotrexate after transplantation. Sirolimus-based GVHD prophylaxis without methotrexate is associated with the greatest overall survival. Myeloablative doses of busulfan should not be used with sirolimus-based immunosuppression.

PMID:
18776081
PMCID:
PMC2597119
DOI:
10.1182/blood-2008-07-169342
[Indexed for MEDLINE]
Free PMC Article
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