CAJ | 학술논문

目的探讨异基因造血干细胞移植(allo-HSCT)并使用高剂量环磷酰胺诱导免疫耐受治疗重型再生障碍性贫血(SAA)的效果和安全性.方法选择2012年8月至2014年8月接受HLA半相合allo-HSCT后应用高剂量环磷酰胺诱导免疫耐受的新方法治疗的20例SAA患者,其中男性12例,女性8例,平均年龄17.8岁(6～37岁),均为HLA半相合HSCT.移植前所有受者均接受过环孢素A治疗,11例接受过抗人淋巴细胞免疫球蛋白(ATG)强化免疫治疗;供者接受了粒细胞集落刺激因子动员,采用供者骨髓和外周血干细胞联合移植;改良的预处理方案为环磷酰胺、氟达拉滨、白消安,移植后3 d使用环磷酰胺(50 mg·kg-1 ·d-1)诱导免疫耐受,移植物抗宿主病(GVHD)的预防采用联合免疫抑制剂包括环孢素A、氨甲蝶呤、他克莫司等,观察移植后受者GVHD、存活等情况.结果 17例受者造血重建,3例受者第二次移植后植入,中性粒细胞≥0.5×109/L及血小板≥20×109/L的平均时间分别为17.4d和21.3 d,植入检测证实为100％完全供者造血,移植前后T淋巴细胞亚群计数水平显著增高.随访至2015年4月,中位随访时间17.7个月(6～32个月),因并发症死亡3例,其余17例受者仍无SAA复发存活,存活率为85％,最长存活时间达32个月.结论减低强度预处理的allo-HSCT并使用高剂量环磷酰胺诱导免疫耐受治疗SAA具有良好的疗效和安全性.
목적 탐토이기인조혈간세포이식(allo-HSCT)병사용고제량배린선알유도면역내수치료중형재생장애성빈혈(SAA)적효과화안전성.방법 선택2012년8월지2014년8월접수HLA반상합allo-HSCT후응용고제량배린선알유도면역내수적신방법치료적20례SAA환자,기중남성12례,녀성8례,평균년령17.8세(6～37세),균위HLA반상합HSCT.이식전소유수자균접수과배포소A치료,11례접수과항인림파세포면역구단백(ATG)강화면역치료;공자접수료립세포집락자격인자동원,채용공자골수화외주혈간세포연합이식;개량적예처리방안위배린선알、불체랍빈、백소안,이식후3 d사용배린선알(50 mg·kg-1 ·d-1)유도면역내수,이식물항숙주병(GVHD)적예방채용연합면역억제제포괄배포소A、안갑접령、타극막사등,관찰이식후수자GVHD、존활등정황.결과 17례수자조혈중건,3례수자제이차이식후식입,중성립세포≥0.5×109/L급혈소판≥20×109/L적평균시간분별위17.4d화21.3 d,식입검측증실위100％완전공자조혈,이식전후T림파세포아군계수수평현저증고.수방지2015년4월,중위수방시간17.7개월(6～32개월),인병발증사망3례,기여17례수자잉무SAA복발존활,존활솔위85％,최장존활시간체32개월.결론 감저강도예처리적allo-HSCT병사용고제량배린선알유도면역내수치료SAA구유량호적료효화안전성.
Objective The study was aimed to explore the efficacy and safety of allogeneic stem cell transplantation (allo-HSCT) with high-dose cyclophosphamide-induced immune tolerance in the treatment of severe aplastic anemia(SAA).Method 20 cases with SAA received reducing the intensity conditioning allo-HSCT from 2012 August to 2014 August,it is a new method for post-transplantation with high-dose cyclophosphamide-induced immune tolerance,including 12 males and 8 females,the age ranged from 6 to 37 years old,and the average age of 17.8 years old,all are HLA-mismatched transplantation and received CsA therapy,eleven of them received ATG intensive immune therapy.The donors accepted mobilization with cell colony stimulating factor from both peripheral blood and bone marrow.The improved Preconditioning regimen was reduced strength of fludarabine combined with Busulfex and cytarabine、cyclophosphamide.Cyclophosphamide (50mg/Kg/d) induced immune tolerance on the + 3 days after transplantation,combined immunosuppressive agents were used for graft-versus-host disease (GVHD) prophylaxis,including CsA,Amethopterin,tacrolimus,etc..and observed toxicity、GVHD and disease-free survival in patients after transplantatior.Result 17 cases of hematopoietic reconstitution and the other three cases implants after the second transplantion,the average time were 17.4 d and 21.3 d respectively with neutrophils≥0.5 × 109/L and platelets≥20 × 109/L.Implantation was confirmed by the evidence of 100％ of donor hematopoiesis and T lymphocyte subsets counts increased significantly before and after the transplantation.Follow-up to 20t5 April,With the median follow-up duration of 17.7 months (6～32 months),3 cases died of complication and the other 17 patients remained disease-free survival,disease-free survival rate was 85 ％ and the longest disease-free survival time up to 32 months.Conclusion Reduced intensity allogeneic hematopoietic stem cell transplantation with high-dose cyclophosphamide-induced immune tolerance treatment is the safe and effective method for severe aplastic anemia.