High-dose cyclophosphamide-induced immunogenic tolerance following haploidentical allogeneic hematopoietic stem cell transplantation in severe aplastic anemia children

doi:10.3969/j.issn.2095-4344.2016.32.016

Abstract

Abstract:

BACKGROUND: High-dose cyclophosphamide (CTX)-induced immunogenic tolerance following haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) is developed to optimize the treatment of childhood severe aplastic anemia (SAA) using haplotype allo-HSCT, providing a theoretical basis for the clinical application.
OBJECTIVE: To investigate the clinical efficacy and safety of the use of high-dose CTX following haploidentical allo-HSCT in SAA children.
METHODS: Clinical data from 10 children with SAA undergoing haploidentical allo-HSCT at the Department of Hematology, General Hospital of Beijing Military Area from January 2013 to January 2015 were retrospectively analyzed. Pretreatment was CTX, fludarabine, Busulfex combined with anti-human lymphocyte immune globulin used for 2 consecutive days, and then 3 days after transplantation, CTX (50 mg/kg per day) was used to induce immunogenic tolerance. Combined use of cyclosporin A, methotrexate and tacrolimus functioned as a prophylaxis for graft-versus-host disease. Another 10 SAA children who underwent synchronous HLA-identical sibling HSCT served as controls. Complications and survival in children were statistically analyzed in the two groups.
RESULTS AND CONCLUSION: In the treatment group, children were followed up until May 2015, and the median follow-up period was 18.1 months (5-28 months). Hematopoietic reconstruction was successful in all cases, and there were three cases of graft-versus-host disease, three cases of pulmonary infection and two cases dying of pulmonary infection. In the control group, the median follow-up period was 20.7 months (6-27 months), and all the children received hematopoietic reconstruction. Additionally, there were two cases of graft-versus-host disease, four cases of pulmonary infection, one case dying of graft-versus-host disease and one case dying of pulmonary infection in the control group. The total survival rate in each group was 80%. In summary, high-dose CTX-induced immunogenic tolerance is safe and effective for SAA children undergoing haploidentical allo-HSCT, which makes the clinical efficacy of haploidentical allo-HSCT identical to that of matched HSCT.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Anemia, Aplastic, Haploidy, Hematopoietic Stem Cell Transplantation, Immune Tolerance, Cyclophosphamide, Tissue Engineering

CLC Number:

R394.2

Guo Zhi, Tong Chun, Liu Xiao-dong, Yang Kai, He Xue-peng, Zhang Yuan, Chen Peng, Lou Jin-xing, Chen Hui-ren. High-dose cyclophosphamide-induced immunogenic tolerance following haploidentical allogeneic hematopoietic stem cell transplantation in severe aplastic anemia children[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(32): 4818-4824.

Figures/Tables 1

2.1 造血重建两组均随访至2015年5月，治疗组随访5-28个月，中位随访时间为18.1个月，10例患儿均获造血重建，中性粒细胞≥0.5×109 L-1的平均时间为15.8 d，血小板≥20×109 L-1的平均时间为22.2 d。对照组随访6-27个月，中位随访时间为20.7个月，10例患儿均获造血重建，中性粒细胞≥0.5×109 L-1的平均时间为15.4 d，血小板≥20×109 L-1的平均时间为21.3 d。全部患儿均能较好耐受预处理方案，预处理期间无严重并发症发生。 2.2 移植相关并发症治疗组中发生移植物抗宿主病3例，其中急性移植物抗宿主病2例，Ⅲ度和Ⅳ度各1例，慢性移植物抗宿主病1例，移植物抗宿主病发生率为30%，按照发生部位分为肠道1例、肝脏1例、皮肤1例，最终1例患儿因Ⅳ度肝脏移植物抗宿主病无法控制死亡，移植后还发生肺部感染3例，最终有1例患儿因肺部侵袭性真菌感染出现呼吸窘迫综合征死亡，其余8例患儿均存活，移植后还发生败血症2例、出血性膀胱炎2例、巨细胞病毒血症及皮肤软组织感染各1例，均得到有效控制。对照组10例患儿中，2例发生移植物抗宿主病，均为急性，移植物抗宿主病发生率为20%，部位均在肠道，分度为Ⅲ度，最终都能有效控制，4例发生肺部感染，因肺部感染死亡2例，这2例患儿都是因为弥漫性肺炎无法控制死亡，其余8例患儿均存活。 2.3 移植疗效全部患儿自移植结束后开始随访观察，随访至2015年5月，中位随访时间19.4个月(5-28个月)，通过统计生存情况，治疗组患儿因并发症死亡2例，其余8例存活，总生存率为80%，最长生存时间已达28个月，对照组患儿因并发症死亡2例，其余8例存活，总生存率为80%，最长生存时间已达27个月，两组患儿总生存率无显著差异。两组患儿生存曲线见图1。"

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