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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4425-4431. Prepublished online as a Blood First Edition Paper on September 5, 2008; DOI 10.1182/blood-2008-07-169342. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-169342v1 112/12/4425    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cutler, C. Articles by Soiffer, R. Search for Related Content PubMed PubMed Citation Articles by Cutler, C. Articles by Soiffer, R. Related Collections Transplantation Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation Corey Cutler1,2, Kristen Stevenson3, Haesook T. Kim3, Paul Richardson1, Vincent T. Ho1, Erica Linden1, Carolyn Revta1, Ruth Ebert1, Diane Warren1, Sung Choi2,4, John Koreth1, Philippe Armand1, Edwin Alyea1, Shelly Carter2,5, Mary Horowitz2,6, Joseph H. Antin1,2, and Robert Soiffer1,2 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; 2 Blood and Marrow Transplant Clinical Trials Network, Rockville, MD; 3 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; 4 University of Michigan Medical Center, Ann Arbor; 5 EMMES Corporation, Rockville, MD; and 6 The Center for International Blood and Marrow Transplant Research, Milwaukee, WI 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Y. H. Leung and Y.-L. Kwong Haematopoietic stem cell transplantation: current concepts and novel therapeutic strategies Br. Med. Bull., November 8, 2009; (2009) ldp040v1. [Abstract] [Full Text] [PDF] Sirolimus and Veno-Occlusive Disease Journal Watch Oncology and Hematology, January 6, 2009; 2009(106): 2 - 2. [Full Text]

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