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Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation. Blood 2008 Dec 01;112(12):4425-31 PMID: 18776081 PMCID: PMC2597119

Pubmed ID

18776081

DOI

10.1182/blood-2008-07-169342

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.

Author List

Cutler C, Stevenson K, Kim HT, Richardson P, Ho VT, Linden E, Revta C, Ebert R, Warren D, Choi S, Koreth J, Armand P, Alyea E, Carter S, Horowitz M, Antin JH, Soiffer R

Author

Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-58149388343   91 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Drug Combinations
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Hepatic Veno-Occlusive Disease
Humans
Immunosuppressive Agents
Incidence
Leukemia
Lymphoma
Male
Middle Aged
Retrospective Studies
Sirolimus
Transplantation Conditioning
Transplantation, Homologous
Young Adult
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5