Humanized anti-CD25 monoclonal antibody treatment of steroid-refractory acute graft-versus-host disease: a Chinese single-center experience in a group of 64 patients.
Humanized anti-CD25 monoclonal antibody treatment of steroid-refractory acute graft-versus-host disease: a Chinese single-center experience in a group of 64 patients.
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人源化抗CD25单克隆抗体治疗类固醇难治性急性移植物抗宿主病：中国单中心64例患者的经验
DOI：
10.1038/bcj.2015.33
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发表时间：
2015-04-17
影响因子：
12.8
通讯作者：
Xue SL
中科院分区：
文献类型：
--
作者：
Tao T;Ma X;Yang J;Zou JY;Ji SM;Tan YS;Gong W;Du F;Xu J;Ye CM;Tang XW;Wu DP;Xue SL
同种异体造血干细胞移植是治疗恶性血液病的一种潜在的治疗方法。然而，急性移植物抗宿主病（aGVHD），特别是难治型，仍然是成功的同种异体造血干细胞移植的严重障碍。已经提出了各种二线治疗方案；然而，到目前为止，还没有标准的治疗方案被证明是最佳选择。抗cd25单克隆抗体（mAb）是类固醇难治性aGVHD最常用的二线治疗选择之一。不幸的是，中国在应用抗cd25单抗治疗类固醇难治性aGVHD方面的经验有限。在此，我们报告了我们在一组受类固醇难治性aGVHD影响的中国同种异体移植患者中使用人源化抗cd25单抗治疗的经验。2011年12月至2014年4月，苏州大学第一附属医院血液科确诊为aGVHD的352例患者，其中64例患者对一线治疗无效3，连续入选本研究。在该组患者中，HSCT后类固醇难治性aGVHD发病的中位时间为1.67个月（范围为0.73-14.2个月）。本研究方案经苏州大学第一附属医院机构审查委员会批准，年龄小于18岁的患者或其监护人签署知情同意书。患者特征总结于表1，并根据Keystone 1994共识标准对aGVHD的严重程度进行分级。4在使用标准剂量甲基强的松龙（2mg/kg/天）治疗时，如果aGVHD在3天内仍进展，或治疗5-7天后仍未缓解，则认为aGVHD是类固醇难治性的，可以给予二线治疗，1同时，类固醇应逐渐减少。5 .与daclizumab （Zenapax, Roche, Nutley， NJ， USA）具有相同氨基酸序列的人源化抗cd25单抗（Xenopax, CP Guojian Pharm, Shanghai, China）在第1、4、8、15和22天以1 mg/kg的剂量静脉注射。如果皮肤或胃肠道aGVHD对全身糖皮质激素治疗没有反应，则分别给予局部作用的软膏或胶囊糖皮质激素，以避免由于全身类固醇逐渐减少而导致aGVHD恶化。在我们的研究中，患者的反应是在治疗开始后的第28天得出的。8完全缓解（CR）的定义是aGVHD在所有器官的所有体征和症状的消退，而不需要介入挽救性治疗；部分缓解（PR）是指在一个或多个器官中至少有一个阶段的改善，而在任何其他器官中没有进展。无应答（NR）定义为治疗开始后28天内没有改善或aGVHD进展。先前的研究表明，daclizumab治疗类固醇耐药aGVHD可产生29%至68%的反应率。然而，我们的结果甚至更多
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic approach for hematologic malignancies. However, acute graft-versus-host disease (aGVHD), especially the refractory type, remains a serious barrier to successful allo-HSCT. Various second-line treatment regimens have been proposed; yet, to date, no standard treatment protocol has proven to be the best choice. 1 The anti-CD25 monoclonal antibody (mAb) is one of the most used second-line treatment choices for steroid-refractory aGVHD. 2 Unfortunately, China has limited experience with regard to the application of anti-CD25 mAb in the treatment of steroid-refractory aGVHD. Herein, we report our experience with humanized anti-CD25 mAb treatment in a group of Chinese allo-HSCT patients affected by steroidrefractory aGVHD.Between December 2011 and April 2014, 352 patients were diagnosed with aGVHD at the Department of Hematology in the First Affiliated Hospital of Soochow University, and 64 patients did not respond to first-line treatment 3 and they were enrolled into this study consecutively. The median time of steroid-refractory aGVHD onset after HSCT was 1.67 months (range, 0.73-14.2 months) in this group of patients. The institutional review board of the First Affiliated Hospital of Soochow University approved this study protocol and the signed informed consent was provided by the enrolled patients or their guardians if the patients were younger than 18 years old. The patient characteristics are summarized in Table 1, and the severity of aGVHD was graded according to the Keystone 1994 consensus criteria. 4 On using standard-dose methylprednisolone (2mg/kg/day) treatment, if aGVHD still progressed within 3 days or if it was not alleviated after treatment for 5-7 days, then the aGVHD is considered steroid refractory and second-line therapy can be given, 1 and simultaneously, the steroid should be tapered. 5 Humanized anti-CD25 mAb (Xenopax, CP Guojian Pharm, Shanghai, China) that has the same amino-acid sequence as daclizumab (Zenapax, Roche, Nutley, NJ, USA) was administered at a dosage of 1 mg/kg intravenously on days 1, 4, 8, 15 and 22. 6 If the skin or gastrointestinal tract aGVHD did not respond to the systemic glucocorticoid treatment, topically worked glucocorticoid in ointment or capsule was given to avoid the exacerbation of aGVHD due to the tapering of systemic steroid, respectively. 7 In our study, the responses of patients were concluded at day 28 after therapy initiation. 8 Complete response (CR) was defined as resolution of all signs and symptoms of aGVHD in all organs without intervening salvage therapy; and partial response (PR) was an improvement of at least one stage in one or more organs without progression in any other organ. No response (NR) was defined as the absence of improvement or aGVHD progression within 28 days after therapy initiation. Previous studies have demonstrated that daclizumab treatment for steroid-resistant aGVHD could produce a response rate ranging between 29 and 68%. 2 However, our results were even more
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影响因子：
5.3
作者：
Li, Jing;Li, Xinyan;Guo, Yajun
通讯作者：
Guo, Yajun
影响因子：
20.3
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Hockenbery, David M.;Cruickshank, Scott;McDonald, George B.
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McDonald, George B.
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作者：
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Feugier, Pierre
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Wingard, John R.;Majhail, Navneet S.;Socie, Gerard
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Socie, Gerard
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作者：
Stanzani, M;Martins, SLR;Komanduri, KV
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Komanduri, KV