摘要
目的初步探讨异基因造血干细胞移植(HSCT)治疗范可尼贫血(FA)的疗效,为探索更加优化移植方案提供依据。方法回顾性分析2012年6月-2016年12月我院收治5例FA患儿进行HSCT的临床资料并复习相关文献。5例患儿中2例行非血缘相合HSCT治疗,3例行单倍体HSCT治疗。预处理方案以氟达拉滨(Flu)、低剂量环磷酰胺(CTX)、抗人胸腺/T淋巴细胞免疫球蛋白(ATG-G/F)为主干,根据移植前输血总量、是否合并白血病,在主干基础上±白消安(Bu)或±全身照射(TBI)。5例患儿回输CD34^+细胞中位计数为8.46(5.46~15.29)×10~6/kg,单个核细胞(MNC)中位计数为13.07(8.33~14.26)×10~8/kg。采用他克莫司和吗替麦考酚酯联合预防移植物抗宿主病(GVHD)。随访中位时间40.7(15~42)个月。结果 5例患儿HSCT预处理过程中,除1例合并严重消化道黏膜反应,其余耐受性尚可;中性粒细胞恢复中位时间10(8~13)d,血小板恢复中位时间16(12~61)d,无原发性植入失败发生;移植后3例发生移植物排斥,分别通过停用全部免疫抑制剂、回输供者干细胞后恢复为完全供者型;4例发生不同程度急性GVHD,3例需升级为二线免疫抑制治疗控制病情,2例发展为慢性GVHD;随访至2016年12月,2例无事件存活,2例存在慢性GVHD,目前病情控制理想,1例死亡。4例存活患儿移植后血细胞未再检测出FA相关基因突变,生长发育同正常同龄儿童,目前尚未发现合并实体肿瘤。结论对于缺乏同胞相合供者的FA患者,其他类型HSCT治疗采用"Flu+低剂量CTX+ATG±Bu或±TBI"预处理方案耐受性尚可,无原发性植入失败发生,但加用Bu或TBI对预处理相关毒性及远期预后的影响还需要深入研究;移植物排斥和GVHD仍是影响患儿生存主要因素,探索个体化、优化HSCT方案治疗FA的临床研究已成为必然。
Objective Allogeneic hematopoietic stem cell transplantation（HSCT） for treatment of Fanconi anemia（FA） effect was discussed in order to explore the optimal transplantation scheme.Methods The clinical data of 5 children with FA treated by HSCT in our hospital from June 2012 to December 2016 were retrospectively analyzed and the related literatures were reviewed.2 cases were treated with unrelated HSCT therapy,and the other 3 cases were treated with haplo-HSCT therapy.Preconditioning regimen was based on fludarabine（Flu）,low dose cyclophosphamide（CTX）,anti-human thymus/T lymphocyte immunoglobulin（ATG-G/F）.According to the total amount of blood transfusion before transplantation,whether or not combined with leukemia,TBI and Bu were chosen to add to the basic preconditioning regimen or not.The median number of CD34^＋ cells in 5 cases was 8.46（5.46-15.29） × 10^6/kg,and the median number of mononuclear cells（MNC） was 13.07（8.33-14.26） × 10^8/kg.Tacrolimus and mycophenolate mofetil were combined to prevent the graft versus host disease（GVHD）.The median follow-up time was 40.7（15-42） months.Results In the process of preconditioning,except 1 cases with severe digestive tract mucosa reaction,the rest can be tolerated;The median time of neutrophil recovery was 10（8-13） d,and the median time of platelet recovery was16（12-61） d.No primary implant failure occurred.Allograft rejection occurred in 3 cases after transplantation,however,after discontinuation of all immunosuppressive agents and donor stem cells infusion,chimerism was restored to complete donor type.4 cases of aGVHD occurred in varying degrees,3 cases needed to be upgraded to second-line immunosuppressive treatment to control the GVHD.And2 cases were developed to chronic GVHD respectively.All cases were followed up until December 2016,and 2 cases were survived without any disease.2 cases had chronic GVHD and both of them were under controlled well.1 case died.FA related gene mutations could not be detected in 4 cas
出处
《中国小儿血液与肿瘤杂志》
CAS
2017年第3期131-137,共7页
Journal of China Pediatric Blood and Cancer
关键词
范可尼贫血
儿童
造血干细胞移植
移植物排斥
移植物抗宿主病
Fanconi anemia
children
Hematopoietic stem cell transplantation
Graft rejection
Graft versus host disease
