SEARCH:   Advanced

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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 18, 2008 Accepted August 23, 2008 Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation Corey Cutler*, Kristen Stevenson, Haesook T Kim, Paul Richardson, Vincent T Ho, Erica Linden, Carolyn Revta, Ruth Ebert, Diane Warren, Sung Choi, John Koreth, Philippe Armand, Edwin Alyea, Shelly Carter, Mary Horowitz, Joseph H Antin, and Robert Soiffer Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, United States Department of Medical Oncology, University of Michigan Medical Center, Ann Arbor, MI, United States EMMES Corporation, Rockville, MD, United States Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, United States * Corresponding author; email: corey_cutler{at}dfci.harvard.edu. Sirolimus is an effective agent used in 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 Cy/TBI conditioning, sirolimus is associated with an increased incidence of VOD (OR 2.35, P=0.005). The concomitant use of methotrexate led to this increased rate of VOD (OR 3.23, P<0.001), while sirolimus without methotrexate was not associated with an increased risk of VOD (OR 1.55, P=0.33). Mortality after VOD diagnosis was unaffected, and overall TRM 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=0.008). Our findings suggest that sirolimus use is associated with VOD after TBI-based transplantation, and this is potentiated by concomitant methotrexate administration. However, sirolimus-based GVHD prophylaxis without methotrexate is associated with the greatest overall survival, because of decreases in other transplant-related complications. Myeloablative doses of busulfan should not be used with sirolimus-based immunosuppression. This trial is registered at www.clinicaltrials.gov under identifier NCT00406393. 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]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020