新型儿童单倍体造血干细胞移植体系治疗儿童血液病结果初探——一个单中心回顾性分析

New haploidentical hematopoietic stem cell transplantation in treatment of hematological diseases in children-single center retrospective analysis

目的探索采用新型儿童单倍体造血干细胞移植（haplo—HSCT）技术体系治疗儿童血液病的安全性和疗效。方法具备HSCT适应症的血液病患儿共56例，均采用新型儿童haplo-HSCT技术体系治疗，回顾性分析植入成功率、移植关死亡率、GVHD发生率、总生存率及无病生存率情况。结果56例血液病患儿中，男34例，女22例，恶性血液病45例，再生障碍性贫血10例，家族性噬血细胞综合征l例，新型haplo—HSCT技术体系治疗后评价：（1）回输单个核细胞中位数为10．59（6．36～13．74）×10^8／kg，CD34＋细胞中位数为7．02（2．00～25．86）×10^6／kg。全部植入成功；（2）干细胞回输后100d内，移植相关死亡率为1．8％；（3）100d内自然发生Ⅰ～Ⅱ度急性移植物抗宿主病（GVHD）发生率为32．14％，Ⅲ～Ⅳ度急性GVHD发生率为1．8％；100d后为治疗和预防复发所进行的供者淋巴细胞输注及减停免疫抑制剂相关的Ⅲ～Ⅳ度急性GVHD发生率5．36％（3例）。100d后自然发生的广泛型慢性GVHD总发生率为3．6％，为治疗和预防复发所进行的DLI及减停免疫抑制剂导致的慢性广泛型GVHD发生率5．36％；（4）中位随访18（6～40．8）个月，总生存率（OS）92．85％，无病生存率（DFS）为87．5％，复发2例，出现微小残留病2例，观察期超过1年的38例病例中，1年OS为92．11％，1年DFS为89．47％。中位生存时间为20．35个月。采用SPSS20．0 Log-Rank法比较淋系和髓系恶性血液病总生存及DFS分别为87．5％和95％（P=0．347）及75％和95％（P=0．058）。结论本研究初步显示对于无相合同胞供者、不能及时寻找到非血缘HLA相合供者的儿童血液病患者，本中心所采用的新型haplo－HSCT技术体系有效性及安全性可靠，淋系及髓系两组比较虽然差异无显著性，但是显示髓系恶性血液病DFS优于淋系的趋势，更远期的疗效尚须更长随访时间进一步总结。

Objective To retrospectively analyze the clinical efficacy of New pediatric haploidentical hematopoietic stem cell transplantation in treatment of children with hematological diseases. Methods Fifty-six children with hematological diseases received New pediatric haploidentical hematopoietic stem cell transplantation, and engraftment, transplant related mortality, incidence of GVHD, OS and DFS, were analysed respectively. Results Fifty-six cases, male 34 cases, female 22 cases, 45 cases of malignant blood diseases, 10 cases of aplastic anemia syndrome, 1 cases of familial hemophagoeytic lympho-histiocytosis, （1） The median mononuclear cells was 10.59 （6.36 -13.74）×10^8/kg,the median CD34 ＋ cells was 7.02（2. 00 -25.86）× 10^6/kg. All the 56 patients achieved full engraftment. （2） Within 100 days after stem cell infusion, the transplant related mortality wasl. 8%. （3） Incidence of Ⅰ - Ⅱ and Ⅲ - Ⅳ degree acute GVHD was 32.14% and 1.8% in 100 days after transplantation, respectively, and the total incidence of extend chronic GVHD was 3.6% . The 3 cases of Ⅲ - Ⅳ degree acute GVHD and 3 cases extend chronic GVHD induced by reduction of immunosuppression or donor lymphocyte infusion. （4） The median follows up is 18 （ 6 - 40.8 ） months, the overall survival（OS） and desease free survival（DFS） were 92.85% and 87.5% respectively. 38 cases were followed up more than 1 year, thel-year OS and DFS were 92. 11% and 89. 47% respectively. Median survival time was 20. 35 months. 2 Cases are relapsed, and 2 cases occurred minimal residual leukemia. Using SPSS 20.0 Log-Rank method to compare the lymphoid and myeloid malignancies in two groups of overall survival and disease-free survival rates were 87.5 % and 95 % （ P = 0.347） and 75% and 95% （ P = 0. 058 ）. Conclusions Show that New haploidentical hematopoietic stem cell transplantation is an effective and feasible treatment in children with hematological diseases and without HLA-identical sibling and unrelated HLA-matched donors. The early efficacy and safety is reliable, long-term effect still need longer follow-up time. It shows a trend of DFS from myeloid malignant is better than that of lymphoid malignancies.