Tumor necrosis factor-α 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, Richard Champlin

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    217 Scopus citations

    Abstract

    Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor-α (TNF-α) 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-α, blocking its interaction with receptors and causing lysis of cells that produce TNF-α. 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 Aspargillus 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.

    Original languageEnglish (US)
    Pages (from-to)649-654
    Number of pages6
    JournalBlood
    Volume104
    Issue number3
    DOIs
    StatePublished - Aug 1 2004

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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  • Cite this

    Couriel, D., Saliba, R., Hicks, K., Ippoliti, C., De Lima, M., Hosing, C., Khouri, I., Andersson, B., Gajewski, J., Donato, M., Anderlini, P., Kontoyiannis, D. P., Cohen, A., Martin, T., Giralt, S., & Champlin, R. (2004). Tumor necrosis factor-α blockade for the treatment of acute GVHD. Blood, 104(3), 649-654. https://doi.org/10.1182/blood-2003-12-4241