造血干细胞移植与非移植治疗重型再生障碍性贫血的比较

Comparison of hematopoietic stem cell transplantation and non-transplantation for treatment of severe aplastic anemia

背景:造血干细胞移植是公认的重型再生障碍性贫血最好的治疗办法。国内外已经开始进行了多种造血干细胞来源的移植,包括亲缘单倍体移植、非血缘移植,而联合间充质干细胞移植提高疗效的报道多为单独个案报道。目的:回顾性对比分析造血干细胞移植与非移植治疗重型再生障碍性贫血的疗效。方法:2008-04/2010-04住院的17例重型再生障碍性贫血患者,年龄3～53岁,8例患者接受造血干细胞移植,9例患者接受了非移植治疗。移植组的8例患者分别接受了亲缘HLA半相合(4例)、HLA相合(2例),非血缘(2例)的造血干细胞移植,在所有移植的患者中有4例在造血干细胞输注的同时静脉输注体外培养扩增的间充质造血干细胞。非移植治疗组9例患者主要采用免疫抑制剂和促造血治疗。结果与结论:移植组除1例45岁患者接受过非移植方法治疗11个月无效,合并肾功能衰竭、肺部真菌感染时才行造血干细胞移植,死于移植合并症外,余7例患者移植后染色体及DNA指纹检测等说明造血干细胞移植完全供者植入,造血功能恢复快,中性粒细胞达到0.5×109L-1,血小板计数≥20×109L-1中位时间分别为12d和14d;其中接受间充质干细胞输注的4例患者平均中性粒细胞达到0.5×109L-1,血小板计数≥20×109L-1的中位时间均为11.6d。移植患者发生Ⅰ,Ⅱ度急性移植物抗宿主病4例,局限慢性移植物抗宿主病者4例,移植后生活质量良好,无需血制品输注,无严重感染和出血。而非移植组患者治疗后造血功能均未恢复正常,1例死于脑出血和感染,余患者生活质量低下,需要反复住院对症治疗,长期间断的血制品输注;治疗后出现多种严重的合并症。结果表明造血干细胞移植是高效的治疗重型再生障碍性贫血的方法,患者造血恢复快,移植物抗宿主病可以预防和控制,生活质量高,疗效明显优于非移植治疗。

BACKGROUND：Hematopoietic stem cell （HSC） transplantation is an optimal therapeutic method of severe aplastic anemia. The transplantation of various sources-derived HSCs has been performed,including affinity haploid transplantation,unrelated transplantation. However,the reports on curative effects of HSCs combined with MSCs transplantation are individual case. OBJECTIVE：To retrospectively compare and analyze the curative effect of HSC transplantation and non-transplantation in treatment of severe aplastic anemia. METHODS：We studied 17 patients with severe aplastic anemia aged 3-53 years from April 2008 to April 2010. In them,8 patients were subjected to HSC transplantation,and 9 patients were treated with non-transplantation. In the transplantation group,4 patients received related HLA half-matched,2 received HLA matched,and 2 received unrelated HSC transplantation. In all patients,4 of them also received mesenchymal stem cell co-transplantation besides HSC infusion. The 9 patients in non-transplantation group received immunosuppressant and hematopoietic promotion treatment. RESULTS AND CONCLUSION：One 45-years old patient in the transplantation group had received non-transplantation for 11 months,but no effect was determined; thus,the patient received transplantation when this patient was combined with renal failure and lung fungous infection,and died of transplantation complication. The chromosome and DNA fingerprint detection of the remaining 7 patients indicated that complete donor implantation and rapid recovery of hematopoietic functions following HSC transplantation. The mean time of neutrophil exceeded 0.5×109/L and platelets recovery exceeded 20×109/L were 12 and 14 days for all transplantation patients,respectively after transplantation,and 11.6 days （neutrophil exceeded 0.5×109/L） and 11.6 days （platelets recovery exceeded 20×109/L） in HSC co-transplants with MSC respectively after transplantation. Four patients received degrees Ⅰ and Ⅱ acute graft versus host disease,and four received limited chronic graft versus host disease. The quality of life of post-transplant patients was good,without blood products infusion or severe infection or bleeding. The hematopoietic function of patients in the non-transplantation group was not recovered to normal. One patient died of cerebral hemorrhage and infection. The remaining patients had low quality of life,and should be hospitalized for symptomatic treatment,long-term discontinuous blood products infusion. Following treatment,many kinds of severe complications occurred. Results suggested that HSC transplantation is highly effective method for treating severe aplastic anemia. The hematopoietic function can be rapidly recovered. Graft versus host disease can be prevented and controlled,showing high quality of life. The curative effect is obviously better compared with non-transplantation.