Jaiswal Sarita Rani, Agarwal Mahak, Bhagawati Gitali, Das Bhudev Chandra, Baligar Prakash, Garg Manoj, Biswas Subhrajit, Chakrabarti Suparno
Department of Blood and Marrow Transplantation, Dharamshila Narayana Superspeciality Hospital and Research Centre, New Delhi, India; Cellular Therapy and Immunology, Manashi Chakrabarti Foundation, Kolkata, India; Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh, India.
Department of Blood and Marrow Transplantation, Dharamshila Narayana Superspeciality Hospital and Research Centre, New Delhi, India; Cellular Therapy and Immunology, Manashi Chakrabarti Foundation, Kolkata, India.
Transplant Cell Ther. 2024 Jun;30(6):605.e1-605.e13. doi: 10.1016/j.jtct.2024.03.010. Epub 2024 Mar 13.
Haploidentical (haplo) hematopoietic cell transplantation (HCT) for nonmalignant disease (NMD) carries inherent challenges of both alloreactivity and graft failure. Building on promising results from pilot studies in which abatacept was combined with post-transplantation cyclophosphamide (PTCy) and sirolimus (AbaCyS) in younger NMD patients undergoing haplo-HCT, we present the long-term outcomes of this protocol. On the back of uniform disease-specific conditioning regimens containing antithymocyte globulin 4.5 mg/kg from day -9 to day -7, GVHD prophylaxis with AbaCyS consisted of abatacept administered on days 0, +5, +20, +35, and monthly until 180 days with PTCy and sirolimus. The patients were followed up with longitudinal assessment of immune reconstitution, growth, and reproductive development and quality of life (QoL) analyses. Among 40 patients (aplastic anemia, n = 24; hemoglobinopathies, n = 14; and primary immunodeficiencies, n = 2) with a median age of 10 years (range, 2 to 25 years), 95% achieved sustained engraftment. Post-transplantation hemophagocytic syndrome was detected in 3 patients, leading to graft failure in 2 cases. The incidence of acute graft-versus-host disease (GVHD) was 2.6%, and that of chronic GVHD (cGVHD) was 14.3%. Cytomegalovirus, adenovirus, and Epstein-Barr virus infections were observed in 45%, 5%, and 0% respectively. Rates of nonrelapse mortality, overall survival, event-free survival, and GVHD-free, event-free survival were 5%, 95%, 90%, and 82%, respectively, at a median follow-up of 4.6 years. Absence of cGVHD correlated with younger patient age and early sustained recovery of regulatory T cells and mature natural killer cells, which in turn was associated with improved QoL and lack of late infections. The AbaCyS protocol was associated with excellent long-term survival, with attenuation of both early and late alloreactivity in >80% of younger patients undergoing haplo-HCT for NMD. This study sheds light on predispositions to cGVHD and its impact on QoL, warranting further optimization of this approach.
单倍体相合造血细胞移植（haplo-HCT）治疗非恶性疾病（NMD）存在同种异体反应性和移植物失败等固有挑战。基于前期研究的 promising 结果，即在接受单倍体-HCT 的年轻 NMD 患者中，将阿巴西普与移植后环磷酰胺（PTCy）和西罗莫司联合使用（AbaCyS），我们展示了该方案的长期结果。在从第-9 天至第-7 天使用 4.5mg/kg 抗胸腺细胞球蛋白的统一疾病特异性预处理方案的基础上，AbaCyS 的移植物抗宿主病（GVHD）预防措施包括在第 0、+5、+20、+35 天给予阿巴西普，并每月一次直至 180 天，同时使用 PTCy 和西罗莫司。对患者进行了免疫重建、生长、生殖发育和生活质量（QoL）分析的纵向评估随访。在 40 例患者中（再生障碍性贫血，n = 24；血红蛋白病，n = 14；原发性免疫缺陷，n = 2），中位年龄为 10 岁（范围 2 至 25 岁），95%实现了持续植入。3 例患者检测到移植后噬血细胞综合征，2 例导致移植物失败。急性移植物抗宿主病（GVHD）的发生率为 2.6%，慢性 GVHD（cGVHD）的发生率为 14.3%。分别有 45%、5%和未观察到爱泼斯坦-巴尔病毒感染。在中位随访 4.6 年时，非复发死亡率、总生存率、无事件生存率和无 GVHD 无事件生存率分别为 5%、95%、90%和 82%。无 cGVHD 与患者年龄较小以及调节性 T 细胞和成熟自然杀伤细胞的早期持续恢复相关，这反过来又与生活质量改善和无晚期感染相关。AbaCyS 方案与出色的长期生存率相关，在接受单倍体-HCT 治疗 NMD 的 80%以上年轻患者中，早期和晚期同种异体反应性均得到减轻。这项研究揭示了 cGVHD 的易患因素及其对生活质量的影响，值得进一步优化这种方法。
