非亲缘HLA表型不全相合供者造血干细胞移植治疗重型β地中海贫血的临床研究

Clinical study of unrelated mismatched hematopoietic stem cell transplantation forβ-thalassemia major

目的探讨非亲缘不全相合供者造血干细胞移植治疗重型β地中海贫血的疗效及安全性。方法回顾性分析2018年1月至2022年4月厦门大学附属中山医院收治的因重型β地中海贫血接受非亲缘不全相合异基因造血干细胞移植(allo-HSCT)15例儿童受者的临床资料。15例均有1~2个HLA位点不相合,其中男8例,女7例;年龄7岁(3~12)岁;铁蛋白水平3417.3(223~14485)μg/L。预处理采用,由氟达拉滨(Flu)、白消安(Bu)和环磷酰胺(CTX)组成的FBC方案。移植物抗宿主病(GVHD)防治方案由环孢素(CsA)、吗替麦考酚酯(MMF)、抗人胸腺细胞免疫球蛋白(ATG)联合低剂量后置环磷酰胺(PTCy)和间充质干细胞组成。结果共完成移植15例;截至2022年4月1日,随访时间为24.1个月(11~49)个月;干细胞植入均成功,植入分析为完全供者嵌合体。中性粒细胞和血小板植入时间分别是12 d(11~22)d和14 d(8~38)d。死亡2例,预期2年的总生存率(OS)和无地中海贫血生存率(TFS)为86.67%。其中,移植后发生Ⅱ度以下急性移植物抗宿主病(aGVHD)5例,Ⅲ~Ⅳ度aGVHD 2例,局限型慢性移植物抗宿主病(cGVHD)3例,无广泛型cGVHD发生。巨细胞病毒和EB病毒均有5例受者激活。结论非亲缘HLA表型不全相合供者HSCT用于重型β地中海贫血的治疗是安全可行的。

Objective To explore the efficacy and safety of unrelated mismatched hematopoietic stem cell transplantation(HSCT)for thalassemia major.Methods For this retrospective cohort study,15 patients withβ-thalassemia major underwent unrelated mismatched HSCT between January 2018 and April 2022.There were 8 males and 7 females with a median age of 7(3-12)years and a median ferritin level of 3417.3(223-14485)μg/L.The conditioning regimens on the basis of fludarabine(Flu),busulfan(Bu)and cyclophosphamide(CTX)and GVHD prophylaxis on the basis of cyclosporine(CsA),mycophenolate mofetil(MMF),anti-human thymocyte immunoglobulin(ATG)plus low-dose post-cyclophosphamide(PTCy)and mesenchymal stem cells were offered.Results Up until April 1,2022,15 children were successfully implanted during a median follow-up period of 24.1(11-49)months and all of them achieved stable donor chimerism.The median time to neutrophil and platelet engraftment were 12(11-22)and 14(8-38)days respectively.Except for 2 deaths,13 cases survived.The estimated 2-year probability of overall survival(OS)and thalassemia-free survival(TFS)were both 86.67%.There were 5 cases of acute graft versus host disease(aGVHD)below gradeⅡ,2 cases of gradeⅢtoⅣaGVHD,and 3 cases of localized chronic graft versus host disease(cGVHD)after transplantation.No gengralized cGVHD occurred.Both cytomegalovirus and Epstein-Barr virus were activated in five recipients.Conclusions Unrelated mismatched donor HSCT is both safe and feasible for thalassemia major.