Sirolimus for treatment of steroid-refractory acute graft-versus-host disease
Sirolimus for treatment of steroid-refractory acute graft-versus-host disease
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DOI：
10.1038/bmt.2009.343
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发表时间：
2010-08-01
影响因子：
4.8
通讯作者：
Kharfan-Dabaja, M. A.
中科院分区：
文献类型：
--
作者：
Hoda, D.;Pidala, J.;Kharfan-Dabaja, M. A.
急性GVHD（aGVHD）是造血移植受者发病和死亡的主要原因。对全身性糖皮质激素无效或不耐受的患者的最佳治疗仍不明确。我们在34例患者中评价了西罗莫司的疗效，中位年龄为49（23-67）岁，患有类固醇难治性（n = 31）或类固醇不耐受性（n = 3）aGVHD。aGVHD在同种异体移植后中位数34（7-1042）天被诊断，并在所有病例中通过活检证实。初始aGVHD治疗由高达2 mg/kg的泼尼松组成。西罗莫司在开始糖皮质激素治疗后中位9（1-255）天开始治疗。34例患者中有19例（56%）接受西罗莫司负荷剂量给药，中位剂量为6（3-8）mg，随后维持1-2 mg/天，以达到4 - 12 ng/ml的目标治疗谷水平。总有效率为76%。34例患者中有15例（44%）达到CR，定义为在西罗莫司开始治疗后，在没有额外免疫抑制剂的情况下，aGVHD完全消退持续至少1个月。31例激素难治性患者中有11例（42%）和3例激素不耐受患者中有2例（67%）达到CR。开始西罗莫司治疗后的中位OS为5.6个月，1年OS为44%（95% CI：27-60%）。西罗莫司可有效控制类固醇难治性aGVHD。骨髓移植（2010）45，1347-1351; doi：10.1038/bmt.2009.343; 2009年12月7日在线发表
Acute GVHD (aGVHD) is a major cause of morbidity and mortality in hematopoietic allograft recipients. The best therapy for patients failing to respond, or not tolerating, systemic glucocorticoids remains undefined. We evaluated the efficacy of sirolimus in 34 patients, median age of 49 (23-67) years, with steroid-refractory (n = 31) or steroid-intolerant (n = 3) aGVHD. aGVHD was diagnosed at a median of 34 (7-1042) days post allografting, and confirmed by biopsy in all cases. Initial aGVHD treatment consisted of prednisone up to 2 mg/kg. Sirolimus was initiated at a median of 9 (1-255) days after glucocorticoid initiation. A sirolimus loading dose was administered to 19 (56%) of 34 patients, median 6 (3-8) mg, followed by maintenance of 1-2 mg/day to target therapeutic trough levels between 4 and 12 ng/ml. Overall response rate was 76%. Fifteen (44%) of 34 patients achieved CR, defined as complete resolution of aGVHD sustained for at least 1 month, after sirolimus initiation without additional immunosuppressive agents. CR was achieved in 11 (42%) of 31 steroid-refractory and 2 (67%) of 3 steroid-intolerant patients. Median OS after initiation of sirolimus was 5.6 months, and 1-year OS was 44% (95% CI: 27-60%). Sirolimus is effective in controlling steroid-refractory aGVHD. Bone Marrow Transplantation (2010) 45, 1347-1351; doi: 10.1038/bmt.2009.343; published online 7 December 2009