自体脐血干细胞移植成功治愈儿童重型再生障碍性贫血

Successful autologous cord blood transplantation for pediatric acquired severe aplastic anemia

目的:探索自体脐血干细胞移植治疗儿童重型再生障碍性贫血的可行性及安全性。方法:自2011年8月—2020年3月,确诊为获得性重型再生障碍性贫血且出生时留存自体脐血的4例患儿,其中男、女各2例,年龄分别为3、4、7和12岁,发病至自体移植时间间隔均值为2个月。移植预处理方案为:抗胸腺免疫球蛋白2.5 mg/(kg·d)×5 d联合环磷酰胺40 mg/(kg·d)×2 d。回输脐带血单个核细胞及CD34^(+)细胞总量分别为(2.92~4.90)×10^(7)/kg、(0.43~0.73)×10^(5)/kg,3例患儿在0天同时输注了自体脐带间充质干细胞0.5×106/kg。移植后+1天给予重组人粒细胞集落刺激因子5~10μg/kg,皮下注射,至中性粒细胞植入。回输后+1天开始口服环孢素3~6 mg/(kg·d),移植后6个月开始缓慢减量至停药。随访时间截至2020年8月31日。结果:4例患儿均获得了完全血液学缓解。中性粒细胞植入时间分别为移植后+16天、+20天、+29天、+37天,血小板植入时间分别为移植后+33天、+27天、+22天、+40天,血常规完全正常时间分别为回输后+59天、+70天、+86天、+90天。随访时间最长107个月,最短6个月,均未发生第二肿瘤、生长发育迟缓或脏器功能受损等不良反应,治疗过程中无严重不良事件发生。3例自体脐血联合间充质干细胞移植的患儿停用环孢素后血常规稳定,1例单纯脐血干细胞移植者需环孢素较长时间维持。结论:自体脐血干细胞移植治疗儿童重型再生障碍性贫血的疗效确定、安全,可作为此类重症疾病的治疗选择,联合间充质干细胞移植可能会促进更快速稳定的造血恢复。

Objective: To observe the efficacy and safety of autologous cord blood transplantation for children with acquired severe aplastic anemia(SAA). Methods: From August 2011 to March 2020, 4 children diagnosed as acquired SAA with autologous cord blood available were enrolled, including 2 boys and 2 girls, ranged from 3-12 years old. The average interval from onset to treatment time was 2 months. The conditioning regimen included antithymocyte globulin 2.5 mg/(kg·d) for 5 days and cyclophosphamide 40 mg/(kg·d) for 2 days. The total mononuclear cells and CD34 positive cells number was(2.92-4.90) ×10^(7)/kg and(0.43-0.73) ×10^(5)/kg, respectively. Three patients were co-infused with autologous mesenchymal stem cells at day 0 with the total number of 0.5×10^(6)/kg. Recombinant human granulocyte colony stimulating factor was subcutaneously injected with 5-10 μg/kg until neutrophil engraftment from day 1. Cyclosporine A was initiated from day 1 for 6 months and then tapered slowly. All the patients were followed-up to August 31, 2020. Results: All 4 children had a complete hematologic response, with the interval to achieving normal blood counts of 59 days, 70 days, 86 days and 90 days, respectively. The time to neutrophil engraftment was day+16, day+20, day+29, day+37, respectively, and the time to platelet engraftment was day+33, day+27, day+22 and day+40, respectively. Follow-up time ranged from 6 months to 107 months, during which there were no obvious adverse events such as second malignant tumors, growth retardation or organ dysfunction. Interestingly, children with mesenchymal stem cells co-transplanted had stable hematologic response, while 1 patient received continuous cyclosporine A maintenance treatment. Conclusion: Autologous umbilical cord blood transplantation combined with cyclosporine A is safe and effective and might be considered as initial therapy for acquired SAA patients. Co-infusing mesenchymal stem cells with autologous umbilical cord blood transplantation may promote stabilized hematopoietic recovery.