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

Publication Type
Journal Article
Year of Publication
2008
Authors
Cutler, Corey; Stevenson, Kristen; Kim, Haesook T; Richardson, Paul; Ho, Vincent T; Linden, Erica; Revta, Carolyn; Ebert, Ruth; Warren, Diane; Choi, Sung; Koreth, John; Armand, Philippe; Alyea, Edwin; Carter, Shelly; Horowitz, Mary; Antin, Joseph H; Soiffer, Robert
Secondary
Blood
Volume
112
Pagination
4425-31
Date Published
2008 Dec 01
Keywords
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
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.