非血缘脐血造血干细胞移植治疗戈谢病三例并文献复习  

Treatment of Gaucher disease with allogeneic hematopoietic stem cell transplantation： report of three cases and review of literatures

作　　者：唐湘凤[1] 栾佐[1] 吴南海[1] 章波[1] 井远方[1] 杜宏[1] 卢伟[1] 徐世侠 

机构地区：[1]解放军海军总医院儿科,北京100048 [2]解放军海军总医院信息科,北京100048

出　　处：《中华儿科杂志》2015年第11期810-816,共7页Chinese Journal of Pediatrics

摘　　要：目的探讨非血缘脐血造血干细胞移植（UCBT）治疗戈谢病的效果。方法回顾性分析2013年4月至2014年9月我院收治3例戈谢病患儿进行UCBT的临床资料，以“戈谢病”“异基因造血干细胞移植”“Gaucher diseases”“allogeneic hematopoietic stem cell transplantation”为关键词，应用万方医学网、pubmed数据库对1983年至2015年的文献进行检索及总结。结果3例戈谢病患儿均为女性，移植年龄分别为3．8岁、7．1岁和2．6岁，其中例2为二次移植，例1和例3移植前行脾脏切除术，预处理选用白消安＋氟达拉滨＋环磷酰胺＋兔抗人胸腺细胞免疫球蛋白，二次移植者在此基础上加用马法兰。预防移植物抗宿主病（GVHD）采用环孢素A和吗替麦考酚酯。输注脐血干细胞中有核细胞数分别为9．7×10^7／kg、11．9×10^7／kg和7．6×10^7／kg，CD34^＋细胞数分别为5．4×10^5／kg、3．5×10^5／kg和3．2×10^5／kg。中性粒细胞绝对数〉0．5×10^9／L的天数分别是移植后11d（＋11d）、＋12d和＋19d，血小板〉20×10^9／L的天数分别是＋14d、＋33d和＋74d，移植后1个月（＋1月）均达到供者型完全嵌合，葡糖脑苷脂酶（GBA）恢复正常。期间3例均出现人巨细胞病毒和EB病毒血症。例1在＋5月出现激素依赖性免疫性血小板减少症，给予间充质干细胞输注血常规恢复正常，＋9月在院外传染水痘致全身播散性感染死亡，死亡前GBA保持正常水平，无慢性GVHD。例2为GBA保持正常水平，无慢性GVHD发生，无病生存。例3GBA保持正常水平，＋112d出现慢性GVHD，为皮肤局限性，激素可控制，现无病生存。3例患儿在GBA恢复正常后，肝脏和脾脏均明显回缩。复习文献发现通过异基因造血干细胞移植治疗戈谢病共50例，均为国外报道。总体无病生存率达85％。在31例有戈谢病分型报道中，Ⅰ型22例，Ⅲ型9例。在29例有生存报道的病例中，Objective To explore the efficacy of unrelated umbilical cord blood transplantation （UCBT） in the treatment of Gaucher disease. Method The clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietie stem cell transplantation （aIIo-HSCT） in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried. Result Three children with Gaueher disease, all were female, received UCBT. These patients＇ age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received spleneetomy before UCBT. The pretreatment regimen was busulfan （Bu）/ fludarabine （Flu）/cyclophosphamide （CTX）/antithymocyte globulin （ATG）, and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil （MMF） wee used for prophylaxis of acute graft versus host disease （aGVHD）. The dose of cord blood stem cell nucleated cell counts was 9. 7 × 10^7/kg, 11.9 × 10^7/kg and 7.6 × 10^7/kg respectively. The dose of cord blood stem cell CD34 ^＋ cell counts was 5.4 × 10^5/kg , 3.5× 10^5/kg and 3.2 × 10^5/kg respectively. The day of granuloeytes exceeding 0. 5 × 109^/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 10^9/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of β-glueocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus （ CMV ） and Epstein- Barr virus （EBV） viremia. In case 1 immune thromboeytopenia occurred at five month

关 键 词：戈谢病 造血干细胞移植 脐血干细胞移植 

分 类 号：R725.9[医药卫生—儿科]