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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2003-02-0489. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-02-0489v1 102/5/1601    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 Antin, J. H. Articles by Soiffer, R. J. Search for Related Content PubMed PubMed Citation Articles by Antin, J. H. Articles by Soiffer, R. J. Related Collections Immunobiology Neoplasia Transplantation Immunotherapy Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2003, Vol. 102, No. 5, pp. 1601-1605 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation Joseph H. Antin, Haesook T. Kim, Corey Cutler, Vincent T. Ho, Stephanie J. Lee, David B. Miklos, Ephraim P. Hochberg, Catherine J. Wu, Edwin P. Alyea, and Robert J. Soiffer From the Department of Medical Oncology and Biostatistical Science, DanaFarber Cancer Institute, Department of Medicine, Brigham & Women's Hospital, Boston, MA. We studied the feasibility and activity of adding sirolimus to tacrolimus and low-dose methotrexate as graft-versus-host disease (GVHD) prophylaxis in recipients of alternative donor transplants. Forty-one patients with hematologic malignancies were conditioned with cyclophosphamide and total body irradiation. Marrow stem cells were from an HLA-A, -B, and -DR compatible, unrelated donor (n = 26, 68%), froma5of6 antigen-matched unrelated donor (n = 8, 20%), or from a 5 of 6 antigen-matched family member (n = 5, 12%). Therapeutic serum levels of sirolimus were attained in most patients. All evaluable patients engrafted. An absolute neutrophil count of 500/µL was achieved on day +18 (range, 11-32 days). Sustained platelet counts of more than 20 000/ µL were attained on day +29 (range, 14-98 days). Grades 0-I acute GVHD occurred in 75% of patients. Grades II, III, and IV acute GVHD occurred in 13%, 8%, and 5%, respectively (total grades II-IV GVHD, 26%). Median survival is 366 days (95% CI 185, not estimable) and actuarial survival at 1 year is 52%. Oral sirolimus is tolerable, adequate blood levels are achievable, and there is a low rate of acute GVHD compared with historical data in this high-risk population. This novel agent is worthy of further study in allogeneic transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Armand, S. Gannamaneni, H. T. Kim, C. S. Cutler, V. T. Ho, J. Koreth, E. P. Alyea, A. S. LaCasce, E. D. Jacobsen, D. C. Fisher, et al. Improved Survival in Lymphoma Patients Receiving Sirolimus for Graft-Versus-Host Disease Prophylaxis After Allogeneic Hematopoietic Stem-Cell Transplantation With Reduced-Intensity Conditioning J. Clin. Oncol., December 10, 2008; 26(35): 5767 - 5774. [Abstract] [Full Text] [PDF] C. Cutler, K. Stevenson, H. T. Kim, P. Richardson, V. T. Ho, E. Linden, C. Revta, R. Ebert, D. Warren, S. Choi, et al. Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation Blood, December 1, 2008; 112(12): 4425 - 4431. [Abstract] [Full Text] [PDF] R. J. Maggiore, D. L. Cooper, F. M. Foss, W. D. Shlomchik, and S. E. Seropian Sirolimus-Containing Graft-Versus-Host Disease Prophylaxis and High- Resolution HLA Typing Improves the Outcome of Mismatched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation. Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 2216 - 2216. [Abstract] F. M. Marty, J. Bryar, S. K. Browne, T. Schwarzberg, V. T. Ho, I. V. Bassett, J. Koreth, E. P. Alyea, R. J. Soiffer, C. S. Cutler, et al. Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis Blood, July 15, 2007; 110(2): 490 - 500. [Abstract] [Full Text] [PDF] C. Cutler, S. Li, V. T. Ho, J. Koreth, E. Alyea, R. J. Soiffer, and J. H. Antin Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation Blood, April 1, 2007; 109(7): 3108 - 3114. [Abstract] [Full Text] [PDF] R. Nakamura, R. Rodriguez, A. Nademanee, J. Palmer, D. Senitzer, D. Snyder, J. Zain, V. Pullarkat, S. J. Forman, and P. M. Parker The Use of Sirolimus Combined with Tacrolimus and Low-Dose Methotrexate Is Effective in Preventing Graft-Versus-Host Disease after Unrelated Donor Hematopoietic Stem Cell Transplantation. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 2866 - 2866. [Abstract] [PDF] J. E. Foley, U. Jung, A. Miera, T. Borenstein, J. Mariotti, M. Eckhaus, B. E. Bierer, and D. H. Fowler Ex Vivo Rapamycin Generates Donor Th2 Cells That Potently Inhibit Graft-versus-Host Disease and Graft-versus-Tumor Effects via an IL-4-Dependent Mechanism J. Immunol., November 1, 2005; 175(9): 5732 - 5743. [Abstract] [Full Text] [PDF] M. H. Albert, X.-Z. Yu, P. J. Martin, and C. Anasetti Prevention of lethal acute GVHD with an agonistic CD28 antibody and rapamycin Blood, February 1, 2005; 105(3): 1355 - 1361. [Abstract] [Full Text] [PDF]

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