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Graft-Versus-Host Disease

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept

Summary:

Steroid-resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be associated with a high mortality. We report the results of a phase II study of treatment of steroid-resistant aGVHD with the IL-2 receptor antibody daclizumab combined with the TNF-receptor fusion protein etanercept. Treatment consisted of daclizumab 1 mg/kg given i.v. on days 1, 4, 8, 15, 22 and etanercept 16 mg/m2 s.c. on days 1, 5, 9, 13, 17. A total of 21 patients (age 15–61 years) with steroid-resistant aGVHD after alloHSCT were included in the study. Donor types were HLA-matched related (n=6), HLA-matched unrelated (n=14), and HLA-mismatched unrelated (n=1). Eight patients achieved complete, and six showed partial remission of aGVHD. Seven patients did not respond. Four of 21 patients are currently alive with a median follow-up of 586 (185–1155) days. Three patients died due to relapsed malignancy. Treatment-related mortality was due to infectious complications (n=11) or organ failure due to aGVHD (n=3). In total, 12 patients developed subsequent chronic GVHD. In conclusion, the data demonstrate an acceptable response rate of the combination of daclizumab and etanercept in the treatment of steroid-resistant aGVHD. Nevertheless, long-term mortality due to infectious complications and chronic GVHD remains high.

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Acknowledgements

We thank Florian Buchkremer, Anne Steffen and Andreas Lueck for clinical work as well as Michael Steiner for critical review of the manuscript. Christian Junghanss received support by the DFG, Grant JU 417 2-1.

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Wolff, D., Roessler, V., Steiner, B. et al. Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept. Bone Marrow Transplant 35, 1003–1010 (2005). https://doi.org/10.1038/sj.bmt.1704929

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