Abstract:

ObjectiveTo compare the efficacy of combining haploidentical donor blood and cord bloodstem cell transplantation （Haplo-cord HSCT） with haploidentical stem cell transplantation （Haplo-HSCT） inthe treatment of severe aplastic anemia （SAA） in children. MethodsA retrospective analysis was performed on38 cases of SAA who underwent haplo-HSCT in Department of Hematology and Oncology of Shanghai Children’s Hospitalfrom May 2017 to February 2023. A total number of 21 children with SAA received Haplo-Cord HSCT， while 17 childrenreceived Haplo-SCT. The regimen used myeloablative conditioning （fludarabine， busulfan， cyclophosphamide and rabbit anti-thymocyte globulin）. ResultsNo primary graft failure （PGF） occurred in any of the 21 patients in Haplocord cohort， and one patient developed PGF in the Haplo cohort. Two patients in Haplo-cord cohort and one patient inHaplo cohort developed Secondary graft failure，respectively. The median time for engraftment for granulocytes in the Haplo core group and Haplo group were 12（10，19） d and 11（10，16） d, respectively（P ＝ 0.630）. While the median time for platelet implantation in these groups were 16（12，32） and 16（13，24）d, respectively（P ＝ 0.461）. Patients who underwent an Haplo-cord HSCT had a lower cumulative incidence of Grade Ⅱ to Ⅳ aGVHD compared with the Haplo HSCT cohort 〔（23.8±9.3）% vs. 25±10.8）%，P ＝ 0.770）〕， they also had lower cumulative incidence of Grade Ⅲ to Ⅳ aGVHD comparedto the Haplo cohort 〔（9.5±6.4）% vs.（18.7±9.8）%，P ＝ 0.374）〕. The cumulative incidence of chronic GVHD was （14.3±7.6）% in Haplo-cord cohort and was（33±12.2）% in Haplo cohort（P ＝ 0.226）. The 3-year overall， failure-free， and GVHD failure-free （GFFS） survival rates in Haplo-cord cohort and Haplo cohort were 〔（95.2±4.6）% vs.（85.6±9.7）%， P ＝ 0.405）〕，〔（83.5±8.9）% vs.（82.4±9.2）%，P ＝ 0.642）〕 and 〔（81±8.6）% vs.（52.9±12.1）%，P ＝ 0.046）〕，respectively. We found that cord blood with a high degree of HLA matching and high CD34+ cell counts achieved high GFFS. PCR analyses of short tandem repeats （STR） showed persistent and sustained full haplo donor myeloid chimaerism， withoutany evidence of umbilical cord blood engraftment. We found that Haplo-cord HSCT in children with SAA achieved higher GFFS. Conclusion Haplo-HSCT is an effective treatment for children with SAA， with a high engraftment rate. The coinfusion of an UCB may improve survival of Haplo-HSCT in SAA patients. 

Key words:

Haploidentical hematopoietic stem cell transplantation , Cord blood , Severe aplastic anemia, Children

摘要：

目的 比较是否辅助第三方脐带血在单倍体造血干细胞移植治疗儿童重型再生障碍性贫血的疗效差异。方法 回顾性分析 2017 年 5 月至 2023 年 2 月上海市儿童医院明确诊断为重型或极重型再生障碍性贫血并接受单倍体造血干细胞移植的 38 例患儿的临床资料。其中 21 例患儿接受单倍体造血干细胞联合第三方脐血移植（Haplo-cord HSCT），17 例接受单倍体造血干细胞移植（Haplo-HSCT）。均采用清髓性预处理方案 ：氟达拉滨（Flu）/ 白消安（Bu）/ 环磷酰胺（Cy）+ 兔抗人胸腺细胞球蛋白（rabbit anti-human hymocyte globulin，r-ATG）。结果Haplo-cord 组 21 例患儿均获得造血重建，其中 2 例发生继发性植入失败。Haplo 组中 1 例患儿原发性植入失败，1 例继发性植入失败。Haplo-cord 组和 Haplo 组中性粒细胞植入中位时间分别为12（10，19）和 11（10，16）d（P ＝ 0.630），血小板植入中位时间为 16（12，32）和 16（13，24）d（P ＝0.461）。Haplo-cord 组和 Haplo 组Ⅱ - Ⅳ度急性移植物抗宿主病（acute graft-versus-host disease，aGVHD）、Ⅲ - Ⅳ 度 aGVHD、慢性移植物抗宿主病（chronic graft-versus-host disease，cGVHD）的累积发生率分别为〔（23.8±9.3）% 比（25±10.8）%，P ＝ 0.770〕、〔（9.5±6.4）% 比（18.7±9.8）%，P ＝ 0.374〕、〔（14.3±7.6）% 比（33±12.2）%，P ＝ 0.226〕。两组患儿 3 年总体生存率（overall survival，OS）、无失败生存率（failure free survival，FFS）、无 GVHD/ 无失败生存率（GVHD-free and failure-free survival，GFFS）分别为〔（95.2±4.6）% 比（85.6±9.7）%，P ＝ 0.405〕、〔（83.5±8.9）% 比（82.4±9.2）%，P ＝ 0.642〕、〔（81±8.6）% 比（52.9±12.1）%，P ＝ 0.046〕。 基于短串联重复序列多态性的 STR-PCR 嵌合检测提示移植后获得造血重建的患儿均为完全单倍体供者嵌合。我们发现 Haplo-cord 后置模式治疗儿童重型再生障碍性贫血可获得更高的 GFFS。结论 单倍体造血干细胞移植在治疗儿童重型再生障碍性贫血方面植入率高，疗效确切，辅助输注脐血可能提高移植的总体疗效。 

关键词:

单倍体造血干细胞移植 , 脐带血 , 重型再生障碍性贫血 , 儿童