Humanized anti-CD25 monoclonal antibody for prophylaxis of graft-vs-host disease (GVHD) in haploidentical bone marrow transplantation without ex vivo T-cell depletion
Humanized anti-CD25 monoclonal antibody for prophylaxis of graft-vs-host disease (GVHD) in haploidentical bone marrow transplantation without ex vivo T-cell depletion
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DOI：
10.1016/s0301-472x(03)00228-5
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发表时间：
2003-11-01
影响因子：
2.6
通讯作者：
Xun, CQ
中科院分区：
文献类型：
--
作者：
Chen, HR;Ji, SQ;Xun, CQ
客观的。研究新型抗 IL-2 受体 (CD25) 单克隆抗体巴利昔单抗对移植物抗宿主病 (GVHD) 和半相合骨髓移植 (BMT) 植入的影响。材料和方法。 13 名连续的高危白血病患者（年龄 9-4 1）接受了半相合 BMT，使用 G-CSF 引发的骨髓作为干细胞，没有离体 T 细胞耗竭。巴利昔单抗与环孢素 (CSA)、甲氨蝶呤 (MTX) 和吗替麦考酚酯 (MMF) 联合用于 GVHD 预防。使用免疫表型分析、有限稀释试验和集落形成试验来测量巴利昔单抗对淋巴细胞亚群、细胞毒性 T 淋巴细胞前体 (CTLp) 和造血细胞的影响。结果。所有患者均成功实现了具有完全供体嵌合状态的三系移植。没有患者出现 II-IV 级急性 GVHD。存活超过 12 个月且未复发的患者表现出有限的慢性皮肤 GVHD。 13 名患者中有 10 名目前存活，中位随访时间为 17 个月（范围 1224 个月），卡诺夫斯基评分为 100%。在有限稀释试验中，巴利昔单抗显着降低同种异体反应性 CTLp 10 倍至 100 倍。通过体外集落形成试验确定它对造血干细胞和祖细胞没有影响。结论。在 CSA、MMF 和 MTX 中添加巴利昔单抗作为 GVHD 预防，可有效减少半相合 BMT 中的严重致死性 GVHD。使用抗CD25抗体可以选择性地消除或减少同种异体反应性T细胞的数量，从而预防GVHD或减轻GVHD的严重程度。 (C) 2003 年国际实验血液学学会。由爱思唯尔公司出版
Objective. To investigate the effects of a novel anti-IL-2 receptor (CD25) monoclonal antibody, basiliximab, on graft-vs-host disease (GVHD) and engraftment in haploidentical bone marrow transplantation (BMT).Materials and Methods. Thirteen consecutive high-risk leukemia patients (age 9-4 1) underwent haploidentical BMT with G-CSF-primed marrow as stem cells without ex vivo T-cell depletion. Basiliximab, along with a combination of cyclosporine (CSA), methotrexate (MTX), and mycophenolate mofetil (MMF), was used for GVHD prophylaxis. Immunophenotyping, limited-dilution assay, and colony-forming assays were used to measure the effect of basiliximab on the subsets of lymphocytes, cytotoxic T-lymphocyte precursors (CTLp), and hematopoietic cells.Results. All patients established successful trilineage engraftment with full donor chimerism. No patients developed grade II-IV acute GVHD. Patients who survived more than 12 months and were free of relapse showed limited chronic skin GVHD. Ten of 13 patients are currently alive with a Karnofsky performance score of 100% at median follow-up of 17 months (range 1224 months). Basiliximab significantly decreased alloreactive CTLp by 10-fold to 100-fold in limiting-dilution assays. It had no effect on hematopoietic stem and progenitor cells as determined by in vitro colony-forming assays.Conclusion. The addition of basiliximab to CSA, MMF, and MTX as GVHD prophylaxis effectively reduced severe lethal GVHD in haploidentical BMT. It is possible to selectively eliminate or reduce the number of alloreactive T cells with anti-CD25 antibody, which results in prevention of or a reduction in the severity of GVHD. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc.