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Blood, 1 August 2004, Vol. 104, No. 3, pp. 649-654. Prepublished online as a Blood First Edition Paper on April 6, 2004; DOI 10.1182/blood-2003-12-4241. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4241v1 104/3/649    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 Couriel, D. Articles by Champlin, R. Search for Related Content PubMed PubMed Citation Articles by Couriel, D. Articles by Champlin, R. Related Collections Transplantation Clinical Trials and Observations Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Tumor necrosis factor- blockade for the treatment of acute GVHD Daniel Couriel, Rima Saliba, Krystal Hicks, Cindy Ippoliti, Marcos de Lima, Chitra Hosing, Issa Khouri, Borje Andersson, James Gajewski, Michele Donato, Paolo Anderlini, Dimitrios P. Kontoyiannis, Agueda Cohen, Thomas Martin, Sergio Giralt, and Richard Champlin From the Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX; the Department of Infectious Diseases, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Division of Hematology/Oncology, UCSF Medical Center, San Francisco, CA. Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor- (TNF-) is implicated in the pathophysiology of GVHD at several steps in the process. Infliximab is a genetically constructed immunoglobulin G1 (IgG1) murine–human chimeric monoclonal antibody that binds the soluble subunit and the membrane-bound precursor of TNF-, blocking its interaction with receptors and causing lysis of cells that produce TNF-. In this study we retrospectively evaluated 134 patients who had steroid-refractory acute GVHD. Of these, 21 who received infliximab as a single agent were analyzed. The overall response rate was 67% (n = 14), and 13 patients (62%) experienced complete response (CR). Five patients (24%) did not respond, and 2 (10%) had progressive GVHD. None had a toxic reaction to infliximab. Ten patients (48%) had 18 fungal infections, including Aspergillus species in 7 and Candida species in 10. Seventeen patients (81%) had bacterial infections, including 32 gram-positive and 8 gram-negative infections. Viral infections, primarily cytomegalovirus reactivation, occurred in 14 patients (67%). The Kaplan-Meier estimate of overall survival was 38%. In conclusion, infliximab was well tolerated and active for the treatment of steroid-resistant acute GVHD, particularly with gastrointestinal tract involvement. Survival after steroid-resistant acute GVHD continues to be problematic. The possibility of excessive fungal and other infections must be explored further. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Fatal case of protothecosis in a hematopoietic stem cell transplant recipient after infliximab treatment for graft-versus-host disease Jad A. Khoury, Eric R. Dubberke, and Steven M. Devine Blood 2004 104: 3414-3415. [Full Text] [PDF] This article has been cited by other articles: S. Nishiwaki, S. Terakura, M. Ito, T. Goto, A. Seto, K. Watanabe, M. Yanagisawa, N. Imahashi, S. Tsukamoto, M. Shimba, et al. Impact of macrophage infiltration of skin lesions on survival after allogeneic stem cell transplantation: a clue to refractory graft-versus-host disease Blood, October 1, 2009; 114(14): 3113 - 3116. [Abstract] [Full Text] [PDF] M. J. Carlson, M. L. West, J. M. Coghill, A. Panoskaltsis-Mortari, B. R. Blazar, and J. S. Serody In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations Blood, February 5, 2009; 113(6): 1365 - 1374. [Abstract] [Full Text] [PDF] S. W. Choi, C. L. Kitko, T. Braun, S. Paczesny, G. Yanik, S. Mineishi, O. Krijanovski, D. Jones, J. Whitfield, K. Cooke, et al. Change in plasma tumor necrosis factor receptor 1 levels in the first week after myeloablative allogeneic transplantation correlates with severity and incidence of GVHD and survival Blood, August 15, 2008; 112(4): 1539 - 1542. [Abstract] [Full Text] [PDF] E. R. Brown, K. A. Charles, S. A. Hoare, R. L. Rye, D. I. Jodrell, R. E. Aird, R. Vora, U. Prabhakar, M. Nakada, R. E. Corringham, et al. A clinical study assessing the tolerability and biological effects of infliximab, a TNF-{alpha} inhibitor, in patients with advanced cancer Ann. Onc., July 1, 2008; 19(7): 1340 - 1346. [Abstract] [Full Text] [PDF] J. E. Levine, S. Paczesny, S. Mineishi, T. Braun, S. W. Choi, R. J. Hutchinson, D. Jones, Y. Khaled, C. L. Kitko, D. Bickley, et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease Blood, February 15, 2008; 111(4): 2470 - 2475. [Abstract] [Full Text] [PDF] B. H. Segal Role of Macrophages in Host Defense Against Aspergillosis and Strategies for Immune Augmentation Oncologist, October 1, 2007; 12(suppl_2): 7 - 13. [Abstract] [Full Text] [PDF] M. L. MacMillan, D. Couriel, D. J. Weisdorf, G. Schwab, N. Havrilla, T. R. Fleming, S. Huang, L. Roskos, S. Slavin, R. K. Shadduck, et al. A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease Blood, March 15, 2007; 109(6): 2657 - 2662. [Abstract] [Full Text] [PDF] D. Weisdorf GVHD The Nuts and Bolts Hematology, January 1, 2007; 2007(1): 62 - 67. [Abstract] [Full Text] [PDF] J. J. Fullmer, L. L. Fan, M. K. Dishop, C. Rodgers, and R. Krance Successful Treatment of Bronchiolitis Obliterans in a Bone Marrow Transplant Patient With Tumor Necrosis Factor-{alpha} Blockade Pediatrics, September 1, 2005; 116(3): 767 - 770. [Abstract] [Full Text] [PDF] J. A. Khoury, E. R. Dubberke, and S. M. Devine Fatal case of protothecosis in a hematopoietic stem cell transplant recipient after infliximab treatment for graft-versus-host disease Blood, November 15, 2004; 104(10): 3414 - 3415. [Full Text] [PDF] T. Iwasaki Recent Advances in the Treatment of Graft-Versus-Host Disease Clin. Med. Res., November 1, 2004; 2(4): 243 - 252. 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