Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.
Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.
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DOI：
10.1038/leu.2015.212
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发表时间：
2015-10
期刊：
影响因子：
11.4
通讯作者：
von Bubnoff N
中科院分区：
文献类型：
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作者：
Zeiser R;Burchert A;Lengerke C;Verbeek M;Maas-Bauer K;Metzelder SK;Spoerl S;Ditschkowski M;Ecsedi M;Sockel K;Ayuk F;Ajib S;de Fontbrune FS;Na IK;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 GU;Kuball J;Flynn R;Ihorst G;Du J;Blazar BR;Arnold R;Kröger N;Passweg J;Halter J;Socié G;Beelen D;Peschel C;Neubauer A;Finke J;Duyster J;von Bubnoff N
尽管异基因造血细胞移植在过去的几十年里有了很大的进步，但皮质类固醇难治性(SR)急性(A)和慢性(C)移植物抗宿主病(GVHD)导致了高死亡率。临床前证据表明JAK1/2抑制剂ruxolitinib具有强大的抗炎特性。在这项回顾调查中，欧洲和美国的19个干细胞移植中心报告了95名接受鲁索利替尼抢救治疗SR-GVHD的患者的结果数据。患者分为SR-aGVHD(54例，均为III级或IV级)和SR-cGVHD(41例，均为中、重度)。SR-aGVHD(1-7)和SR-cGVHD(1-10)既往GVHD治疗的中位数均为3。SR-aGVHD的ORR为81.5%(44/54)，其中CR25例(46.3%)，SR-cGVHD的ORR为85.4%(35/41)。鲁索利替尼有效的患者中，SR-aGVHD和SR-cGVHD的GVHD复发率分别为6.8%(3/44)和5.7%(2/35)。SR-aGVHD组和SR-cGVHD组的6个月生存率分别为79%(67.3%~90.7%，95%CI)和97.4%(92.3%~100%，95%CI)。在Ruxolitinib治疗期间，SR-aGVHD(30/54，55.6%)和SR-cGVHD(7/41，17.1%)和SR-cGVHD(6/41，14.6%)患者均出现细胞减少和CMV再激活。Ruxolitinib可能成为治疗SR-aGVHD和SR-cGVHD的一种有前景的新选择，应该在前瞻性试验中得到验证。
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.