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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.
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Submitted December 11, 2003
Accepted March 21, 2004
Tumor necrosis factor alpha blockade for the treatment of steroid-refractory acute GVHD
Daniel R Couriel*, Rima Saliba, Krystal Hicks, Cindy Ippoliti, Marcos J de Lima, Chitra Hosing, Issa Khouri, Borje Andersson, Michele Donato, James Gajewski, Paolo Anderlini, Dimitrios P Kontoyiannis, Aguedo Cohen, Thomas Martin, Sergio Giralt, and Richard Champlin
Blood and Marrow Transplantation, UT MD Anderson Cancer Center, Houston, TX, USA
* Corresponding author; email: dcouriel{at}mdanderson.org.
Despite post-transplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality. Tumor necrosis factor (TNF) alpha has been implicated in the pathophysiology of GVHD at several steps in the process. Infliximab is a genetically constructed IgG1 murine-human chimeric monoclonal antibody that binds both the soluble subunit and the membrane-bound precursor of TNF- alpha, blocking its interaction with receptors and also causing lysis of cells that produce TNF alpha. In this study we retrospectively evaluated 139 patients who developed steroid-refractory acute GVHD. Of these, 26 who received infliximab as a single agent were analyzed. The overall response was 65% (n=17), and most of these patients (62%, n=16) had CR. Nine patients (35%) did not respond (23%, n=6) or had progression (12%, n=3) of their GVHD. There were no toxic reactions to infliximab. Twelve patients (46%) had 21 fungal infections including aspergillus in 8 and candida species in 13. Eighteen patients (69%) had bacterial infections, including gram-positive bacteria (n=35, 73%) and gram-negative rods (n=8, 17%). Viral infections were identified in 15 patients (57%); most of these were secondary to cytomegalovirus reactivation in blood. The Kaplan-Meier estimate of overall survival for all patients from the time of transplant was 31%. TNF-alpha blockade with infliximab was well tolerated and active for the treatment of steroid resistant acute GVHD, particularly with gastrointestinal tract involvement. Survival in steroid resistant acute GVHD continues to be a problem. The possibility of an excess in fungal or other infections needs to be explored further.
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