In Vivo T Cell Costimulation Blockade with Abatacept for Acute Graft-versus-Host Disease Prevention: A First-in-Disease Trial
In Vivo T Cell Costimulation Blockade with Abatacept for Acute Graft-versus-Host Disease Prevention: A First-in-Disease Trial
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DOI：
10.1016/j.bbmt.2013.09.003
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发表时间：
2013-11-01
影响因子：
4.3
通讯作者：
Kean, Leslie S.
中科院分区：
文献类型：
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作者：
Koura, Divya T.;Horan, John T.;Kean, Leslie S.
我们进行了一项首次疾病试验，在非相关供体造血细胞移植（HCT）期间，使用阿巴西普体内CD 28：CD 80/86共刺激阻断剂预防急性移植物抗宿主病（aGVHD）。所有患者在HCT后第-1、+5、+14、+28天接受环孢菌素/甲氨蝶呤加4剂阿巴西普（10 mg/kg/剂）。评估了添加阿巴西普的可行性、其药代动力学、药效学及其对aGVHD、感染、复发和移植相关死亡率（TRM）的影响。所有患者均接受了计划的阿巴西普剂量，未观察到输注反应。与未接受阿巴西普治疗的患者队列相比，（StdRx队列），入组研究的患者（阿坝队列）显示出对早期CD 4（+）T细胞增殖和活化的显著抑制，主要影响效应记忆（Tern）亚群，增殖和活化的CD 4（+）Tern细胞分别减少7倍和10倍，阿坝组与StdRx组相比，在第+28天（P
We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tern) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tern cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P