【摘要】 目的评价异基因外周血造血干细胞移植(allo-PBSCT)治疗重型再生障碍性贫血(SAA)的疗效。方法10例接受allo-PBSCT治疗的SAA患者中,8例为血缘供体移植,2例为无关供体移植。男、女各5例,年龄18～42岁,中位年龄为27岁。3例患者为急性SAA(SAA-Ⅰ型),其中2例患者移植前合并重型感染且未能完全控制;7例患者为慢性SAA(SAA-Ⅱ型),患者移植前大多经包括环孢素(CsA)在内的多种治疗无效。诊断至移植的时间为1～240个月,中位时间为12个月。采用兔抗人T淋巴细胞球蛋白(ATG)+环磷酰胺(CTX)方案:移植前-5～-1d静脉缓慢滴注ATG4～5μg·kg-1.d-1,移植前-4d～-3d静脉滴注CTX60mg·kg-1.d-1;采用CsA+短程甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD)。结果患者移植后均获造血重建,中性粒细胞绝对值≥0.5×109/L和血小板计数≥20×109/L的中位时间分别为移植后+13.2d(+11～+15d)和+14.3d(+13～+15d)。8例患者为完全供体型植入;2例为嵌合状态,其中1例亲缘供体患者予冻存外周血干细胞输注1次即转为完全供体型,另1例无关供体患者移植后3个月出现外周血白细胞、红细胞、血小板计数逐渐下降,DNA短串联重复序列多态性分析(STR-PCR)显示移植排斥,再次行同一供体移植后逐渐恢复自身造血。1例患者出现Ⅱ度急性GVHD,2例出现局限性慢性GVHD。3例患者移植后出现纯红细胞再生障碍,经血浆置换后红系恢复正常造血。随访3～92个月,中位数为33个月,10例SAA患者均存活。结论采用以免疫抑制为主的ATG+CTX的减低剂量预处理方案进行allo-PBSCT能够有效治疗SAA,移植相关并发症少,值得临床推广应用。更多还原

【Abstract】 Objective To evaluate the efficacy of allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) for severe aplastic anemia (SAA). Methods Ten patients with SAA (three were diagnosed as SAA-Ⅰand seven as SAA-Ⅱ,with two complicated with severe infection) received allo-HSCT,including eight receiving from related and two from unrelated donors. The patients included five men and five women,with a median age of 27 years old (range:18-42). Most of patients in our group were treated with CsA and other treatments but were all proven to be ineffective before transplant. The period from diagnosis to transplantation was 1-240 months,with a median time of 12 months. PBSC were mobilized with G-CSF for 5 days. Conditioning regimens included ATG-Fresenius 4-5 μg·kg-1·d-1×4 d plus CTX 60 mg·kg-1·d-1×2 d. CsA and MTX were given to prevent acute graft-versus-host disease (aGVHD). The effectiveness and complications were analyzed retrospectively. Results Hematopoiesis reconstitution was achieved in 9 patients and graft rejection occurred in 1 patient.The median periods for neutrophils to reach 0.5×109/L and platelets to reach 20×109/L were 13.2 (11-15) and 14.3 (13-15) days,respectively. Eight patients were full donor chimerism and two were in mixed chimerism status. One patient with related donor was transferred to full donor chimerism after infusion of frozen peripheral blood hematopoietic stem cells. Another patient with unrelated donor had decreased peripheral white blood cells,red blood cells and platelets three months after transplantation; STR-PCR indicated graft rejection; second transplantation was performed with the same donor and hematopoiesis of the patient origin was achieved gradually. One case developed grade Ⅱ aGVHD and two developed limited cGVHD.Three patients had pure red cell aplasia and achieved hematopoiesis reconstitution after plasma replacement. All the patients survived with a median period of 33 months (3-92) at the end of follow-up. Conclusion Allo-PBSCT with ATG plus CTX as reduced intensity conditioning regimens is an effective therapy for patients with SAA; it has less complication and is worth popularizing in clinical practice.更多还原