Abstract:
Post-allogeneic hematopoietic cell transplant (HCT) immunosuppression regimens are given as graft-versus-host disease (GVHD) prophylaxis. Most GVHD prophylaxis regimens are based on calcineurin inhibitors (CNIs). Unfortunately, CNIs are associated with significant associated morbidity, frequently cannot be tolerated, and often need to be discontinued. There is no consensus as to which alternative immunosuppression should be used in cases where CNIs have to be permanently discontinued. Cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocking agents are well tolerated and have been used extensively in patients with autoimmune disease and as post-transplant immunosuppression. There are two CTLA4-Ig agents: belatacept and abatacept. Belatacept is routinely used in adult kidney transplantation to prevent rejection and abatacept has been approved by the Food and Drug Administration (FDA) for GVHD prophylaxis in patients undergoing a matched or one allele-mismatched unrelated allogenic HCT. Herein, we describe a case in which abatacept was given off-label to replace tacrolimus GVHD prophylaxis in a patient with neurotoxicity undergoing haploidentical HCT. This case suggests that CTLA4-Ig blockade may be a good alternative to a CNI in cases where the CNI needs to be discontinued and warrants further investigation.
摘要:
异基因造血细胞移植(HCT)后免疫抑制方案作为移植物抗宿主病(GVHD)的预防。大多数GVHD预防方案基于钙调磷酸酶抑制剂(CNIs)。不幸的是,CNI与显著的相关发病率相关,往往是不能容忍的,而且经常需要停产。在必须永久停用CNI的情况下,应使用哪种替代免疫抑制尚未达成共识。细胞毒性T淋巴细胞相关蛋白4-免疫球蛋白(CTLA4-Ig)阻断剂耐受性良好,已广泛用于自身免疫性疾病患者和移植后免疫抑制。有两种CTLA4-Ig试剂:belatacept和abatacept。Belatacept通常用于成人肾脏移植以预防排斥反应,而abatacept已被食品药品监督管理局(FDA)批准用于接受匹配或一个等位基因不匹配的无关同种异体HCT的患者的GVHD预防。在这里,我们描述了一例病例,在1例接受单倍体相合HCT的神经毒性患者中,给予abatacept替代他克莫司GVHD预防.这种情况表明,在需要停止CNI并需要进一步调查的情况下,CTLA4-Ig封锁可能是CNI的良好替代品。