Ali Robert, Ramdial Jeremy, Algaze Sandra, Beitinjaneh Amer
Hematology/Medical Oncology Fellow, University of Miami/Miller School of Medicine, Miami, FL 33136, USA.
Internal Medicine Residency Program, University of Miami/Miller School of Medicine, Miami, FL 33136, USA.
Biomedicines. 2017 Nov 29;5(4):67. doi: 10.3390/biomedicines5040067.
Allogeneic hematopoietic stem cell transplant is an established treatment modality for hematologic and non-hematologic diseases. However, it is associated with acute and long-term sequelae which can translate into mortality. Graft-versus-host disease (GVHD) remains a glaring obstacle, especially with the advent of reduced-intensity conditioning. Serotherapy capitalizes on antibodies which target T cells and other immune cells to mitigate this effect. This article focuses on the utility of two such agents: anti-thymocyte globulin (ATG) and alemtuzumab. ATG has demonstrated benefit in prophylaxis against GVHD, especially in the chronic presentation. However, there is limited impact of ATG on overall survival and it has little utility in the treatment context. There may be an initial improvement, particularly in skin manifestations, but no substantial benefit has been elicited. Alemtuzumab has shown benefit in both prophylaxis and treatment of GVHD, but at the consequence of a more profound immunosuppressive phase, mandating aggressive viral prophylaxis. There remains heterogeneity in the doses and regimens of the agents, with no standardized protocol in place. Furthermore, it seems that once steroid-refractory GVHD has been established, there is little that can be offered to offset the ultimately dismal outcome. Here we present a systematic overview of ATG- or alemtuzumab-based serotherapy in the prophylaxis and management of GVHD.
异基因造血干细胞移植是治疗血液系统疾病和非血液系统疾病的一种既定治疗方式。然而,它会引发急性和长期后遗症,可能导致死亡。移植物抗宿主病(GVHD)仍然是一个突出的障碍,尤其是在低强度预处理出现之后。血清疗法利用针对T细胞和其他免疫细胞的抗体来减轻这种效应。本文重点关注两种此类药物的效用:抗胸腺细胞球蛋白(ATG)和阿仑单抗。ATG已证明在预防GVHD方面有益,尤其是在慢性表现方面。然而,ATG对总体生存率的影响有限,在治疗方面效用不大。可能会有初步改善,特别是在皮肤表现方面,但尚未产生实质性益处。阿仑单抗在预防和治疗GVHD方面均显示出益处,但代价是免疫抑制期更深,需要积极进行病毒预防。这些药物的剂量和方案仍存在异质性,尚无标准化方案。此外,一旦确立了对类固醇难治的GVHD,几乎没有什么方法可以改变最终的不良结局。在此,我们对基于ATG或阿仑单抗的血清疗法在预防和管理GVHD方面进行系统综述。