范可尼贫血患儿异基因造血干细胞移植治疗21例长期随访分析

Long term follow-up analysis of 21 children with Fanconi anemia treated with allogeneic hematopoietic stem cell transplantation

目的 探讨儿童范可尼贫血(FA)移植预后及相关危险因素。方法 回顾性分析2016年1月—2019年12月在上海交通大学医学院附属上海儿童医学中心经基因检测确诊FA并进行异基因造血干细胞移植(allo-HSCT)的21例患者。结果 患者起病中位年龄3.8(0.1-10.2)岁,移植中位年龄6.7(0.7-11.2)岁。所有患儿均以全血细胞减少为移植指征,移植前均未发生肿瘤。均应用BU 2天/TBI 3Gy+FC为基础的减低剂量预处理方案。15例患儿接受无关供者移植,5例亲缘供体移植,1例脐血移植。19例采用环孢素A联合甲氨蝶呤,2例采用环孢素A联合吗替麦考酚酯预防移植物抗宿主病(GVHD)。急性GVHD和慢性GVHD累积发生率分别为33%和29%。其中,Ⅲ-Ⅳ度aGVHD累积发生率24%(5例),中重度cGVHD发生率为24%(5例)。中位随访时间为49(2-106.2)个月,总体生存率为62%。死亡原因包括4例死于肠道aGVHD,1例死于肺部cGVHD,1例死于植入失败,1例死于植入物功能不良和1例死于CMV脑炎,未发现继发肿瘤发生。多因素分析提示移植前年龄越大及移植前高血清铁蛋白含量是预后的不良因素(P=0.006&P=0.02)。结论 早期明确诊断,及时开展allo-HSCT治疗有助于改善FA长期治疗效果。

Objective To explore the prognosis and related risk factors of allogeneic hematopoietic stem cell transplantation(allo HSCT) in Fanconi anemia(FA) for children.Methods A retrospective analysis was conducted on 21 patients diagnosed with FA through genetic testing and undergoing HSCT at the Shanghai Children′s Medical Center affiliated with Shanghai Jiao Tong University School of Medicine from January 2016 to December 2019.Results The median onset age of the patient was 3.8(0.1-10.2) years old,and the median age at the time of HSCT was 6.7(0.7-11.2) years old.All patients showed a decrease in whole blood cells as the indication for HSCT,and no tumors occurred before transplantation.The dose-reducted regimen based on 2 days of Busulfan(BU) or 3GY of total body irradiation(TBI) with(Fludarabine + Cyclophosphamide + anti-thymocyte globulin)FC was applied.Fifteen patients received unrelated donor HSCT,five were related donor HSCT,and one was cord blood transplantation.19 cases were treated with cyclosporine A combined with methotrexate,and 2 cases were treated with cyclosporine A combined with mycophenolate mofetil to prevent graft-versus-host disease(GVHD).The cumulative incidence rates of acute GVHD and chronic GVHD were 33% and 29%,respectively.Among them,the cumulative incidence rate of Ⅲ-Ⅳ severe aGVHD was 24%(5 cases),and the incidence rate of moderate to severe cGVHD was 24%(5 cases).The median follow-up time was 49(2-106.2)months,and the overall survival rate was 62%.The causes of death included 4 deaths from intestinal aGVHD,1 death from pulmonary cGVHD,1 death from engraftment failure,1 death from poor graft function,and 1 death from CMV encephalitis,with no secondary tumor found.Multivariate analysis suggests that older age before HSCT and higher serum ferritin levels before HSCT were adverse prognostic factors(P=0.006 & P=0.02).Conclusions Early diagnosis and timely implementation of allo HSCT treatment can improve the long-term treatment effect of FA.