不同的造血干细胞移植方式对重型再生障碍性贫血治疗效果的影响

目的:比较异基因外周造血干细胞移植(Allo-PBSCT)、异基因骨髓移植(Allo-BMT)及Allo-PBSCT和Allo-BMT混合移植3种不同的移植方式治疗重型再生障碍性贫血(SAA)的临床效果。方法:37例SAA患者接受了同胞人类白细胞抗原(HLA)全相合异基因干细胞移植,其中Allo-PBSCT组11例,Allo-BMT组14例,混合移植组12例。观察所有患者移植近期中性粒细胞(Neu)和血小板的造血时间、短小片段重复序列(STR)植入状况、粒细胞缺乏(粒缺)合并感染的发生率、急慢性移植物抗宿主病(GvHD)发生率,以及远期3年植入失败率、病死率和无病生存率。结果:Allo-PBSCT组、Allo-BMT组、混合移植组的Neu造血时间分别为(13.5±2.3)d、(21.2±3.5)d和(14.7±2.4)d,血小板造血时间分别为(24±4)d、(22±5)d和(23±5)d,Allo-PBSCT组和混合移植组的Neu造血时间均短于Allo-BMT组(P均<0.05),而3组间血小板平均造血时间比较差异无统计学意义。3组所有患者在移植后第28日时检测STR均证实为完全供者嵌合体。Allo-PBSCT组和混合移植组粒缺合并感染发生率分别为9%和17%,均明显低于Allo-BMT组的57%(P均<0.05);Allo-PBSCT组GvHD总发生率(包括急性和慢性)为36%,与均无GvHD发生的Allo-BMT组及混合移植组比较差异具统计学意义(P均<0.05);Allo-PBSCT组3年的植入失败率、病死率和无病生存率分别为36%、9%和64%,混合移植组和Allo-BMT组所有患者3年内均无病生存、STR均表现为稳定植入,Allo-PBSCT组3年植入失败率高于混合移植组和Allo-BMT组(P均<0.05),3年无病生存率低于混合移植组和Allo-BMT组(P均<0.05)。结论:在上述3种不同的移植方式中,混合移植同时具有Neu重建快、粒缺合并感染发生率低、GvHD发生率和植入失败发生率低、无病生存率高等优点,临床上可以优先考虑采用此方式进行治疗。

Effect of different methods of haematopoietic stem cell transplantation for the treatment of severe aplastic anemia

Objective：To compare the clinical efficacy of allogeneic peripheral blood stem cell transplantation（Allo-PBSCT）,allogeneic bone marrow transplantation（Allo-BMT） and Allo-PBSCT plus Allo-BMT for the treatment of severe aplastic anemia（SAA）.Methods：Thirty-seven patients with SAA received HLA-matched sibling donor stem cell transplantation（n=11,Allo-PBSCT group.n=14,Allo-BMT group.n=12,Allo-PBSCT plus BMT group）.The mean time of reconsitution of neutrophils（Neu） and platelets（Plt）,short tandem repeats（STR）in detecting the engratment,the incidence of infection with agranulocytosis,and graft versus host diseases（GvHD） were observed.The three-year incidence of graft failure（GF）,mortality and disease-free survival（DFS） after transplantation were also investigated.Results：The mean time of reconsitution of Neu was（13.5±2.3） days、（21.2±3.5） days and（14.7±2.4） days in Allo-PBSCT group,Allo-PBSCT plus BMT group and Allo-BMT group respectively.Significant differences were observed between the front two groups and the latter group（P〈0.05）.The mean time of reconsitution of Plt was（24±4） days、（22±5） days and（23±5）days respectively in Allo-PBSCT group,Allo-PBSCT plus BMT group and Allo-BMT group respectively No statistical difference among the three groups.Full donor chimerism was confirmed in all 37 patients at post-tranplant day28.The incidence of infection with agranulocytosis of Allo-PBSCT group and Allo-PBSCT plus BMT group was 9% and 17% respectively and were lower obviously than that in Allo-BMT group which was 57% and there were statistical differences between the front two groups and the latter group（P〈0.05）.The incidence of GvHD of Allo-PBSCT group was 36% and no GvHD happened in Allo-BMT group and Allo-PBSCT plus BMT group and the statistical differences between the front group and the latter groups was positive respectively（P〈0.05）.The three-year incidence of GF,mortality and DFS in PBSCT group was 36.3%,9.0% and 63.6% respectively.All patients in Allo-PBSCT plus BMT group and Allo-BMT group survived with disease-free and the all STRs showed stable.The incidence of GF in Allo-PBSCT group was higher（P〈0.05） and the probability of DFS was lower than that in Allo-PBSCT plus BMT group and Allo-BMT group（P〈0.05）.Conclusions：Allo-PBSCT plus BMT can be chosen preferentially because of its quicker reconsitution of Neu,lower incidence of infection with agranulocytosis,lower incidence of GF and higher probability of DFS.