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Graft-Versus-Host Disease

Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD

Bone Marrow Transplantation volume 46, pages 430–435 (2011)Cite this article

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Abstract

Treatment options for steroid-refractory GVHD (SR-GVHD) are unsatisfactory and prognosis is poor. Inflammatory cytokines IL-2 and TNF-α are important mediators of GVHD and may be critical targets for therapy. We retrospectively reviewed our experience using combination anti-cytokine therapy of daclizumab and infliximab. Seventeen evaluable patients had a median age of 47 years (range 35–63). The conditioning regimen was myeloablative in 13 and non-myeloablative in 4 cases. GVHD occurred at a median of 49 days after transplant in 12 patients (range 21–231 days) and at a median of 46 days (range 25–119 days) after donor lymphocyte infusion in 5 patients. All patients had persistent or progressive GVHD despite 1–2 mg/kg/day of corticosteroids for a median of 7 days (range 2–26 days). They received a combination of daclizumab and infliximab for acute GVHD IBMTR severity index B (3), C (10) or D (4). Of the 17 patients analyzed, 47% responded to treatment, 24% had complete resolution of symptoms and 24% had partial responses. Survival was limited and all the patients died a median of 6.7 months (range 1.6–26) from transplant and 35 days from initiation of daclizumab/infliximab. This retrospective analysis suggests that combination anti-cytokine therapy with daclizumab/infliximab has significant activity in SR-GVHD, but outcomes remain poor. New methods to prevent and treat GVHD are urgently needed.

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Acknowledgements

This work was supported in part by a grant from the NIH (K24 CA11787901; to DLP).

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  1. Division of Hematology-Oncology, Blood and Marrow Transplant Program, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    A Rager, N Frey, S C Goldstein, R Reshef, E O Hexner, A Loren, S M Luger, A Perl, D Tsai, J Davis, M Vozniak, J Smith, E A Stadtmauer & D L Porter

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Correspondence to A Rager.

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Rager, A., Frey, N., Goldstein, S. et al. Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD. Bone Marrow Transplant 46, 430–435 (2011). https://doi.org/10.1038/bmt.2010.117

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