T cell costimulation blockade for hyperacute steroid refractory graft versus-host disease in children undergoing haploidentical transplantation
T cell costimulation blockade for hyperacute steroid refractory graft versus-host disease in children undergoing haploidentical transplantation
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DOI：
10.1016/j.trim.2016.08.009
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发表时间：
2016-11-01
影响因子：
1.5
通讯作者：
Chakrabarti, Suparno
中科院分区：
文献类型：
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作者：
Jaiswal, Sarita Rani;Zaman, Shamsuz;Chakrabarti, Suparno
超急性3-4级类固醇难治性移植物抗宿主病（SR-GVHD）的预后仍然令人沮丧，尽管大量药物正在单独或联合试验。75例患者在移植后使用环磷酰胺进行T全单倍体移植后，10例（13%）2-20岁的患者发生了超急性SR-GVHD。我们报告了两种不同方案治疗SR-GVHD对这些患者预后的影响。5例患者接受由抗胸腺细胞球蛋白、依那西普和巴昔昔单抗组成的方案A治疗。接下来的5例患者联合阿巴接受T细胞共刺激阻断与依那西普和巴昔昔单抗治疗。第29天和第56天，A方案的总有效率分别为40%和0%，b方案的总有效率分别为100%和40%。治疗失败的主要原因是GVHD的进展和机会性感染。在方案B中获得完全缓解的两名患者是免疫抑制的长期无病幸存者。我们的研究表明，在T完全单倍体移植后，儿童早发性SR-GVHD的结果令人沮丧。然而，abataccept联合抗细胞因子药物似乎产生了令人鼓舞的早期反应，可能值得进一步的研究。(C) 2016 Elsevier B.V.版权所有
The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20 years, developed hyperacute SR-GVHD. We report on the outcome of two different regimens for treatment of SR-GVHD on the outcome of these patients. Five patients were treated in Regimen A consisting of anti-thymocyte globulin, Etanercept and Basiliximab. The next 5 patients were treated combining T cell costimulation blockade with Abatacept along with Etanercept and Basiliximab. The overall response at days 29 and 56 were 40% and 0% with Regimen A and 100% and 40% with Regimen B. The major cause of treatment failure was progression of GVHD and opportunistic infections. Two of the patients achieving a complete remission on Regimen B are long term disease free survivors off immunosuppression. Our study demonstrates the dismal outcome of early onset SR-GVHD in children following T replete haploidentical transplantation. However, the combination of Abatacept with anticytokine agents seems to produce encouraging early response and might warrant further investigation. (C) 2016 Elsevier B.V. All rights reserved.