Calcineurin Inhibitors Replacement by Ruxolitinib as Graft-versus-Host Disease Prophylaxis for Patients after Allogeneic Stem Cell Transplantation
Calcineurin Inhibitors Replacement by Ruxolitinib as Graft-versus-Host Disease Prophylaxis for Patients after Allogeneic Stem Cell Transplantation
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用鲁索替尼替代钙调神经磷酸酶抑制剂作为同种异体干细胞移植后患者的移植物抗宿主病预防
DOI：
10.1016/j.bbmt.2020.01.012
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发表时间：
2020-05-01
影响因子：
4.3
通讯作者：
Huang, He
中科院分区：
文献类型：
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作者：
Zhao, Yanmin;Shi, Jimin;Huang, He
移植物抗宿主病(GVHD)是异基因干细胞移植(allo-SCT)的常见并发症，具有较高的死亡率。尽管钙调神经磷酸酶抑制剂(CNIs)已被广泛应用于GVHD的预防，但急性GVHD(AGVHD)的发生率仍保持在30%至50%左右。此外，一些异基因干细胞移植受者不能耐受CNI。因此，需要改进GVHD预防方法。本研究旨在确定鲁索利替尼对异基因干细胞移植后CNI不耐受患者移植物抗宿主病的预防价值。研究对象为2017年9月至2019年3月在本中心接受allo-SCT后对CNI不耐受的10例恶性血液病患者。这些方案是以清髓白头翁和环磷酰胺方案为基础的。抗胸腺细胞球蛋白(抗胸腺细胞球蛋白)用于人类白细胞抗原半相合血缘供者(HRD)患者，剂量为6 mg/kg。所有患者均接受鲁索利替尼替代CNI预防GVHD。鲁索利替尼每日2次，每次5-10 mg，直到移植后2-3个月，然后逐渐减少，在没有移植物抗宿主病的情况下，+180天停止使用。急性白血病8例，骨髓增生性肿瘤1例，自然杀伤T细胞(NK/T)淋巴瘤1例。供者类型为同胞相合供者3例，人类白细胞抗原半相合亲缘供者7例。所有患者接受CNI加短程甲氨蝶呤预防GVHD，但在移植后45天内对CNI表现出不耐受。鲁索利替尼替代治疗后，仅1例(10%)患者在100天内出现II级皮肤aGVHD，仅1例患者在100天后出现严重aGVHD。2例患者在逐渐减少或停用Ruxolitinib后发展为中/重度慢性移植物抗宿主病(CGVHD)，导致中/重度cGVHD的1年累积发生率为21.4%。巨细胞病毒(CMV)复活4例(40%)，EB病毒(EBV)复活3例(30%)。所有患者均未发生巨细胞病毒病或移植后EBV淋巴组织增生性疾病。中位随访11个月(2~15.5个月)，2例(20%)复发，7例(70%)存活，其中6例(60%)微小残留病阴性，4例停用免疫抑制剂治疗。对于接受allo-SCT后CNI不耐受的患者预防性应用ruxolitinib似乎是安全有效的预防GVHD，但这有待在更大范围的队列中进行进一步研究。(C)2020，由Elsevier Inc.代表美国移植和细胞治疗学会出版
Graft-versus-host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT) that carries a high mortality. Although calcineurin inhibitors (CNIs) have been widely used in GVHD prophylaxis, the incidence of acute GVHD (aGVHD) remains at roughly 30% to 50%. Moreover, some allo-SCT recipients cannot tolerate CNI. Thus, improved GVHD prevention methods are needed. Our study aimed to determine the prophylactic value of ruxolitinib for GVHD in CNI-intolerant patients after allo-SCT. Between September 2017 and March 2019, 10 patients with hematopoietic malignancies after allo-SCT who were intolerant to CNI at our center were enrolled in this study. The regimens were based on a myeloablative busulfan and cyclophosphamide regimen. Antithymocyte globulin was administered to patients with an HLA-haploidentical related donor (HRD) at a dosage of 6 mg/kg. All received ruxolitinib to replace CNI as GVHD prophylaxis. Ruxolitinib was initiated at 5 to 10 mg twice daily until 2 to 3 months post-transplantation and then tapered gradually, and in the absence of GVHD, discontinued by day +180. Eight patients had acute leukemia, 1 patient had myeloproliferative neoplasm, and 1 patient had natural killer T cell (NK/T) lymphoma. The donor type was a matched sibling donor in 3 patients and an HLA-haploidentical related donor (HRD) in 7 patients. All patients received CNI plus short-course of methotrexate as GVHD prophylaxis, but showed intolerance to CNI within 45 days post-transplantation. After ruxolitinib replacement, only 1 patient (10%) developed grade II skin aGVHD within 100 days, and only 1 patient developed severe aGVHD after 100 days. Two patients developed moderate/severe chronic GVHD (cGVHD) after tapering or stopping ruxolitinib, resulting in a 1-year cumulative incidence of moderate/ severe cGVHD of 21.4%. Cytomegalovirus (CMV) reactivation occurred in 4 patients (40%), and Epstein-Barr virus (EBV) reactivation occurred in 3 patients (30%). None of the patients developed CMV disease or EBV post-transplantation lymphoproliferative disorder. After a median follow-up of 11 months (range, 2 to 15.5 months), 2 patients (20%) relapsed and 7 (70%) were alive, of whom 6 (60%) were negative for minimal residual disease and 4 were off immunosuppressant therapy. The prophylactic application of ruxolitinib for CNI-intolerant patients after allo-SCT appears to be safe and effective in preventing GVHD, but this awaits further study in larger cohorts. (C) 2020 Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy