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Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multi-center survey

Item Type:Article
Title:Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multi-center survey
Creators Name:Zeiser, R. and Burchert, A. and Lengerke, C. and Verbeek, M. and Maas-Bauer, K. and Metzelder, S.K. and Spoerl, S. and Ditschkowski, M. and Ecsedi, M. and Sockel, K. and Ayuk, F. and Ajib, S. and de Fontbrune, F.S. and Na, I.K. and Penter, L. and Holtick, U. and Wolf, D. and Schuler, E. and Meyer, E. and Apostolova, P. and Bertz, H. and Marks, R. and Lübbert, M. and Wäsch, R. and Scheid, C. and Stölzel, F. and Ordemann, R. and Bug, G. and Kobbe, G. and Negrin, R. and Brune, M. and Spyridonidis, A. and Schmitt-Gräff, A. and van der Velden, W. and Huls, G. and Mielke, S. and Grigoleit, G.U. and Kuball, J. and Flynn, R. and Ihorst, G. and Du, J. and Blazar, B.R. and Arnold, R. and Kröger, N. and Passweg, J. and Halter, J. and Socie, G. and Beelen, D. and Peschel, C. and Neubauer, A. and Finke, J. and Duyster, J. and von Bubnoff, N.
Abstract:Despite major improvements in allogeneic hematopoietic cell transplantation over the last decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Pre-clinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage-therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grade III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The ORR was 81.5% (44/54) in SR-aGVHD including 25 CRs (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%,95% CI) and 97.4% (92.3-100%,95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and CMV-reactivation were observed during ruxolitinib-treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
Keywords:Adrenal Cortex Hormones, Animal Disease Models, Follow-Up Studies, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Homologous Transplantation, Janus Kinases, Neoplasm Drug Resistance, Neoplasm Staging, Prognosis, Pyrazoles, Recurrence, Retrospective Studies, Salvage Therapy, Survival Rate, Young Adult, Animals, Mice
Source:Leukemia
ISSN:0887-6924
Publisher:Nature Publishing Group (U.K.)
Volume:29
Number:10
Page Range:2062-2068
Date:October 2015
Official Publication:https://doi.org/10.1038/leu.2015.212
PubMed:View item in PubMed

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