CAJ | 학술논문

目的探讨异基因造血干细胞移植(allo-HSCT)时采用含氟达拉滨(Flu)和阿糖胞苷(Ara-C)的白消胺+环磷酰胺方案(BuCy方案)的预处理效果及不良反应.方法 60例髓系恶性血液病患者在allo-HSCT前接受含Flu和Ara-C的BuCy方案预处理,按Bu使用天数(2、3和4 d)将患者分为2d组、3d组及4d组,于移植前第4、3、2天输注Flu,剂量为30 mg·m-2·d-1,在Flu输注完毕后4h开始滴注Ara-C,剂量为2 mg·m-2·d-1.观察预处理相关毒性、植入情况、移植相关并发症、原发病复发、移植相关死亡、受者的无病存活率(DFS)、总存活率及影响疗效的相关因素等.结果所有受者均获得造血重建,中性粒细胞＞0.5×109/L的时间为移植后14d(中位数),血小板＞20×109/L的时间为18 d(中位数).预处理相关毒性有肝功能异常40例,腹泻20例,口腔红斑和溃疡21例,心功能损害4例,经相关处理后缓解.移植相关并发症有严重感染20例,出血性膀胱炎6例,急性移植物抗宿主病(GVHD)10例,慢性GVHD22例,肝静脉闭塞症1例.原发病复发8例,4例经甲磺酸伊马替尼联合供者淋巴细胞输注治疗后获得持续分子生物学缓解,4例死亡.移植相关死亡15例,其中2例死于100d内,除1例死于肝静脉闭塞症外,其余病例死于GVHD.受者的3年DFS、移植相关死亡率及慢性GVHD累积发生率分别为66.6％、27.2％和42.9％.2d组和3d组的3年累积复发率分别为21.0％和1 1.1％(P＞0.05),DFS分别为72.4％和72.2％ (P＞0.05),移植相关死亡率分别为17.9％和23.3％(P＞0.05).4d组的移植相关死亡率明显高于其他两组(P＜0.05),而原发病复发率为0.结论在BuCy基础上联合应用Flu和Ara-C进行预处理,髓外毒性小,原发病复发率低,疗效确切,且严重GVHD发生率较低.
목적 탐토이기인조혈간세포이식(allo-HSCT)시채용함불체랍빈(Flu)화아당포감(Ara-C)적백소알+배린선알방안(BuCy방안)적예처리효과급불량반응.방법 60례수계악성혈액병환자재allo-HSCT전접수함Flu화Ara-C적BuCy방안예처리,안Bu사용천수(2、3화4 d)장환자분위2d조、3d조급4d조,우이식전제4、3、2천수주Flu,제량위30 mg·m-2·d-1,재Flu수주완필후4h개시적주Ara-C,제량위2 mg·m-2·d-1.관찰예처리상관독성、식입정황、이식상관병발증、원발병복발、이식상관사망、수자적무병존활솔(DFS)、총존활솔급영향료효적상관인소등.결과 소유수자균획득조혈중건,중성립세포＞0.5×109/L적시간위이식후14d(중위수),혈소판＞20×109/L적시간위18 d(중위수).예처리상관독성유간공능이상40례,복사20례,구강홍반화궤양21례,심공능손해4례,경상관처리후완해.이식상관병발증유엄중감염20례,출혈성방광염6례,급성이식물항숙주병(GVHD)10례,만성GVHD22례,간정맥폐새증1례.원발병복발8례,4례경갑광산이마체니연합공자림파세포수주치료후획득지속분자생물학완해,4례사망.이식상관사망15례,기중2례사우100d내,제1례사우간정맥폐새증외,기여병례사우GVHD.수자적3년DFS、이식상관사망솔급만성GVHD루적발생솔분별위66.6％、27.2％화42.9％.2d조화3d조적3년루적복발솔분별위21.0％화1 1.1％(P＞0.05),DFS분별위72.4％화72.2％ (P＞0.05),이식상관사망솔분별위17.9％화23.3％(P＞0.05).4d조적이식상관사망솔명현고우기타량조(P＜0.05),이원발병복발솔위0.결론 재BuCy기출상연합응용Flu화Ara-C진행예처리,수외독성소,원발병복발솔저,료효학절,차엄중GVHD발생솔교저.
Objective To analyze the efficacy of Fludarabine (Flu) and Cytos1ne arabinoside (Ara-C) containing preparative regimen in patients with myeloid hematological malignancies receiving allogeneic hematopoietic stem cell transplantation(allo-HSCT),and to explore optimal doses of this combination.Methods From April 2005 to March 2008,a total of 60 consecutive patients with myeloid hematological malignancies were treated with allo-HSCT after completing a Busulfan (Bu)-Cyclophosphamide (Cy) preparative regimen modified by Flu/Ara-c.Results All patients achieved engraftment,the overall median time of neutrophil recovery (＞0.5 × 109/L) and platelet recovery (＞20 × 109/L) were 14 (11-20) and 18 (9-41) days,respectively.No critical regimen related toxicity event was observed during the conditioning.Only 1 patient (1.7％) developed hepatic veno-occlusive disease (VOD),the incidence of treatment-related mortality (TRM) within 100 days was 3.3％.The incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) and chronic graft versus host disease (cGVHD) of the evaluble patients was 16.7％ and 38.6％,respectively.The 3 year disease free survival (DFS),overall survival (OS),relapse rate (RR),TRM and cumulative incidences of cGVHD were 66.6％,70.7％,27.2％,14.7％ and 42.9％,respectively.And patients were divided into subgroups according to the days of intravenous Bu administration to further explore optimal Bu dose.Bu4 subgroup showed a trend towards worse DFS (49.9％ vs.71.7％,P =0.050) due to significantly higher TRM (50.1％ vs.20.3％,P =0.012) compared to the other.And Bu2 and Bu3 regimens led to comparable DFS (72.4％ vs.72.2％,P =0.712),though a higher proportion of patients in Bu2 than in Bu3 subgroup benefited from donor lymphocyte infusion after relapse.Conclusion Bu-Cy regimen modified by Flu/Ara-c has a minimal extrahematalogic toxicity,and resulted in a low risk of relapse,low incidence and severety of GVHD in patients with myeloid hematological malignancies receiving allo-HSCT.In particular,the combination of Bu 3.2 mg/kg/d iv.or 4 mg/kg/d × 3,Cy 50 mg/kg/d × 2,Flu 30 mg/m2/d × 3 and Ara-c 2 g/m2/d × 3 might be a feasible myeloablative conditioning regimen.