Uppuluri Ramya, Swaminathan Venkateswaran Vellaichamy, Ganesan Kavitha, Duraisamy Suresh, Nair Anupama, Muthukumar Vijayshree, Nalla Anuraag Reddy, Balakrishnan Logesh, Raj Revathi
Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, India.
Department of Biostatistics, Apollo Hospitals, India.
Blood Cell Ther. 2024 Aug 9;7(3):95-100. doi: 10.31547/bct-2024-006. eCollection 2024 Aug 25.
We present comparative data of children with Fanconi anemia undergoing haploidentical hematopoietic stem cell transplantation (HSCT) with or without the addition of rabbit anti-thymocyte globulin (r-ATG) to the conditioning regimen.
This retrospective study included children with Fanconi anemia aged up to 18 years who underwent haploidentical HSCT between January 2015 and December 2022. The children were included in two cohorts in this study. Cohort 1 included children who received conditioning with fludarabine/cyclophosphamide/single fraction of 2 Gy TBI. The children in cohort 2 received the same conditioning along with r-ATG. Post-transplant cyclophosphamide was administered at a dose of 25 mg/kg on day3 and day4 in both cohorts.
A total of 35 children were included in the study, 25 in cohort 1 and 10 in cohort 2. Neutrophil engraftment was documented around day 14-16 post infusion in 21 children (84%) in cohort 1 and in 8 children (80%) in cohort 2. There was a significant difference in the incidence of the severity of graft versus host disease (GVHD) between the two cohorts ( = 0.003). In cohort 1, acute GVHD was documented in 17 children (68%), with grade 1/2 skin GVHD in 10 children, and grade 3/4 skin and gut GVHD in 7 children. Grade 4 gut GVHD was the cause of death in three children in cohort 1. In cohort 2, acute GVHD was documented in one child (10%) who had grade 4 skin and gut GVHD and succumbed to the above. Chronic GVHD was noted in nine (36%) children in cohort 1, and in one child (10%) in cohort 2. Cytomegalovirus reactivation was documented in 11 children (44%) in cohort 1 and three children (30%) in cohort 2. Overall survival was found to be 16/25 (64%) in cohort 1, with a median follow-up of 49 months, and 7/10 (70%) in cohort 2, with a median follow-up of 12 months.
Serotherapy with r-ATG significantly reduced the incidence of GVHD from 68% to 10% in children with Fanconi anemia, with an increase in overall survival from 64% to 70%, although it did not affect graft failure. Further studies should focus on decreasing graft failure rates with early HSCT before multiple transfusions.
我们提供了接受单倍体相合造血干细胞移植（HSCT）的范可尼贫血患儿的比较数据，这些患儿的预处理方案中添加或未添加兔抗胸腺细胞球蛋白（r-ATG）。
这项回顾性研究纳入了2015年1月至2022年12月期间接受单倍体相合HSCT的18岁及以下范可尼贫血患儿。本研究将患儿分为两个队列。队列1包括接受氟达拉滨/环磷酰胺/单次2 Gy全身照射预处理的患儿。队列2中的患儿接受相同的预处理并加用r-ATG。两个队列均在移植后第3天和第4天给予25 mg/kg剂量的环磷酰胺。
本研究共纳入35例患儿，队列1中有25例，队列2中有10例。队列1中的21例患儿（84%）和队列2中的8例患儿（80%）在输注后第14 - 16天左右记录到中性粒细胞植入。两个队列之间移植物抗宿主病（GVHD）严重程度的发生率存在显著差异（P = 0.003）。在队列1中，17例患儿（68%）发生急性GVHD，其中10例为1/2级皮肤GVHD，7例为3/4级皮肤和肠道GVHD。4级肠道GVHD是队列1中3例患儿死亡的原因。在队列2中，1例患儿（10%）发生急性GVHD，该患儿有4级皮肤和肠道GVHD并因此死亡。队列1中有9例患儿（36%）出现慢性GVHD，队列2中有1例患儿（10%）出现慢性GVHD。队列1中有11例患儿（44%）记录到巨细胞病毒再激活，队列2中有3例患儿（30%）记录到巨细胞病毒再激活。队列1的总生存率为16/25（64%），中位随访时间为49个月；队列2的总生存率为7/10（70%），中位随访时间为12个月。
r-ATG血清疗法可使范可尼贫血患儿的GVHD发生率从68%显著降低至10%，总生存率从64%提高到70%，尽管它不影响移植失败率。进一步的研究应聚焦于在多次输血前尽早进行HSCT以降低移植失败率。
