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

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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., Burchert, A., Lengerke, C., Verbeek, M., Maas-Bauer, K., Metzelder, S.K., Spoerl, S., Ditschkowski, M., Ecsedi, M., Sockel, K., Ayuk, F., Ajib, S., de Fontbrune, F.S., Na, I.K., Penter, L., Holtick, U., Wolf, D., Schuler, E., Meyer, E., Apostolova, P., Bertz, H., Marks, R., Lübbert, M., Wäsch, R., Scheid, C., Stölzel, F., Ordemann, R., Bug, G., Kobbe, G., Negrin, R., Brune, M., Spyridonidis, A., Schmitt-Gräff, A., van der Velden, W., Huls, G., Mielke, S., Grigoleit, G.U., Kuball, J., Flynn, R., Ihorst, G., Du, J., Blazar, B.R., Arnold, R., Kröger, N., Passweg, J., Halter, J., Socie, G., Beelen, D., Peschel, C., Neubauer, A., Finke, J., 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
Volume:	29
Number:	10
Page Range:	2062-2068
Date:	October 2015
Additional Information:	Copyright © 2015 Macmillan Publishers Limited
Official Publication:	https://doi.org/10.1038/leu.2015.212
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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