Ngwube Alexander, Rangarajan Hemalatha, Shah Niketa
Center for Cancer and Blood Disorders, Phoenix Children's Hospital, 1919 East Thomas Road, Phoenix, AZ 85016-7710, USA.
Division of Pediatric Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, OH, USA.
Ther Adv Hematol. 2023 Feb 9;14:20406207231152644. doi: 10.1177/20406207231152644. eCollection 2023.
Administration of abatacept following transplantation has been reported to inhibit graft rejection and graft--host-disease (GvHD) in mouse models associated with allogeneic hematopoietic stem cell transplant (HSCT). This strategy has recently been adopted in clinical practice for GvHD prevention in human allogeneic HSCT and offers a unique approach to optimizing GvHD prophylaxis following alternative donor HSCTs. When combined with calcineurin inhibitors and methotrexate, abatacept had shown to be safe and effective in preventing moderate to severe acute GvHD in myeloablative HSCT using human leukocyte antigen (HLA) unrelated donors. Equivalent results are being reported in recent studies using alternative donors, in reduced-intensity conditioning HSCT and nonmalignant disorders. These observations have led to hypothesizing that even in the setting of increasing donor HLA disparity, abatacept when given with traditional GvHD prophylaxis does not worsen general outcomes. In addition, in limited studies, abatacept have being protective against the development of chronic GvHD through extended dosing and in the treatment of steroid-refractory chronic GvHD. This review summarized all the limited reports of this novels approach in the HSCT setting.
据报道,在与异基因造血干细胞移植(HSCT)相关的小鼠模型中,移植后给予阿巴西普可抑制移植物排斥反应和移植物抗宿主病(GvHD)。最近,这种策略已在临床实践中用于预防人类异基因HSCT中的GvHD,并为优化替代供体HSCT后的GvHD预防提供了一种独特的方法。当与钙调神经磷酸酶抑制剂和甲氨蝶呤联合使用时,阿巴西普已被证明在使用人类白细胞抗原(HLA)不相关供体的清髓性HSCT中预防中度至重度急性GvHD是安全有效的。最近使用替代供体、减低强度预处理HSCT和非恶性疾病的研究也报告了类似的结果。这些观察结果促使人们推测,即使在供体HLA差异增加的情况下,阿巴西普与传统的GvHD预防措施联合使用也不会恶化总体预后。此外,在有限的研究中,阿巴西普通过延长给药时间对慢性GvHD的发生具有保护作用,并可用于治疗类固醇难治性慢性GvHD。本综述总结了HSCT背景下这种新方法的所有有限报道。