Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey
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Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. / Zeiser, R; Burchert, A; Lengerke, C; Verbeek, M; Maas-Bauer, K; Metzelder, S K; Spoerl, S; Ditschkowski, M; Ecsedi, M; Sockel, K; Ayuketang, Francis Ayuk; 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, Nicolaus ; Passweg, J; Halter, J; Socié, G; Beelen, D; Peschel, C; Neubauer, A; Finke, J; Duyster, J; von Bubnoff, N.
In: LEUKEMIA, Vol. 29, No. 10, 10.2015, p. 2062-8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey
AU - Zeiser, R
AU - Burchert, A
AU - Lengerke, C
AU - Verbeek, M
AU - Maas-Bauer, K
AU - Metzelder, S K
AU - Spoerl, S
AU - Ditschkowski, M
AU - Ecsedi, M
AU - Sockel, K
AU - Ayuketang, Francis Ayuk
AU - Ajib, S
AU - de Fontbrune, F S
AU - Na, I-K
AU - Penter, L
AU - Holtick, U
AU - Wolf, D
AU - Schuler, E
AU - Meyer, E
AU - Apostolova, P
AU - Bertz, H
AU - Marks, R
AU - Lübbert, M
AU - Wäsch, R
AU - Scheid, C
AU - Stölzel, F
AU - Ordemann, R
AU - Bug, G
AU - Kobbe, G
AU - Negrin, R
AU - Brune, M
AU - Spyridonidis, A
AU - Schmitt-Gräff, A
AU - van der Velden, W
AU - Huls, G
AU - Mielke, S
AU - Grigoleit, G U
AU - Kuball, J
AU - Flynn, R
AU - Ihorst, G
AU - Du, J
AU - Blazar, B R
AU - Arnold, R
AU - Kröger, Nicolaus
AU - Passweg, J
AU - Halter, J
AU - Socié, G
AU - Beelen, D
AU - Peschel, C
AU - Neubauer, A
AU - Finke, J
AU - Duyster, J
AU - von Bubnoff, N
PY - 2015/10
Y1 - 2015/10
N2 - Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical 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 grades 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 overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (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% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-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.
AB - Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical 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 grades 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 overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (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% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-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.
KW - Adrenal Cortex Hormones
KW - Adult
KW - Aged
KW - Animals
KW - Disease Models, Animal
KW - Drug Resistance, Neoplasm
KW - Female
KW - Follow-Up Studies
KW - Graft vs Host Disease
KW - Hematologic Neoplasms
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Janus Kinases
KW - Male
KW - Mice
KW - Middle Aged
KW - Neoplasm Staging
KW - Prognosis
KW - Pyrazoles
KW - Recurrence
KW - Retrospective Studies
KW - Salvage Therapy
KW - Survival Rate
KW - Transplantation, Homologous
KW - Young Adult
U2 - 10.1038/leu.2015.212
DO - 10.1038/leu.2015.212
M3 - SCORING: Journal article
C2 - 26228813
VL - 29
SP - 2062
EP - 2068
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 10
ER -
