中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2012年
8期
610-614
,共5页
陈欣%魏嘉璘%黄勇%何祎%杨栋林%姜尔烈%马巧玲%周卢琨%林小婷%申昱妍%冯四洲%韩明哲
陳訢%魏嘉璘%黃勇%何祎%楊棟林%薑爾烈%馬巧玲%週盧琨%林小婷%申昱妍%馮四洲%韓明哲
진흔%위가린%황용%하의%양동림%강이렬%마교령%주로곤%림소정%신욱연%풍사주%한명철
贫血,再生障碍性%造血干细胞移植%同胞供者
貧血,再生障礙性%造血榦細胞移植%同胞供者
빈혈,재생장애성%조혈간세포이식%동포공자
Anemia,aplastic%Hematopoietic stem cell transplantation%Sibling donor
目的 评价人组织相容性抗原(HLA)匹配同胞供者异基因造血干细胞移植(MSD allo-HSCT)治疗重型再生障碍性贫血(SAA)的疗效.方法 回顾性分析2003年5月至2011年5月接受MSD allo-HSCT治疗的41例SAA患者临床资料.男24例、女17例,中位年龄23(5～41)岁.SAA-Ⅰ型患者28例,SAA-Ⅱ型9例,肝炎后再生障碍性贫血4例.异基因骨髓移植(allo-BMT)17例,异基因外周血干细胞移植(allo-PBSCT)24例.预处理方案:环磷酰胺(CY)+抗人胸腺细胞球蛋白(ATG)+氟达拉滨(Flu) 20例,CY+ATG+ Flu+阿糖胞苷(Ara-C)±白消安(Bu)或马法兰(Mel)21例.移植物抗宿主病(GVHD)预防方案:环孢素(CsA)加短疗程甲氨蝶呤(MTX)25例,他克莫司(FK506) 加短疗程甲氨蝶呤(MTX)16例.回输CD34+细胞中位数:allo-BMT组患者3.48(2.39～4.80)×106/kg,allo-PBSCT组患者2.95(1.27～5.98)×106/kg.结果 41例患者移植后均获得造血重建,中性粒细胞(ANC)恢复至≥0.5×109/L的中位时间为移植后14(10～23)d,PLT恢复至≥20×109/L的中位时间为移植后 19(8～38)d.12例(29.3%)患者发生急性GVHD(aGVHD),其中Ⅰ～Ⅱ度11例、Ⅳ度1例.2例患者发生慢性GVHD(cGVHD),局限型与广泛型cGVHD各 1例.4例(9.8%)患者出现移植排斥(GR),行供者外周血干细胞输注后均恢复造血并存活.41例患者中死亡5例(12.2%):1例死于广泛型cGVHD、4例死于侵袭性真菌感染(IFI).中位随访23(3～79)个月,36例患者生存,预期5年总体生存(OS)率为(81.1±9.0)%、无病生存(DFS)率为(68.4±11.0)%、移植相关死亡(TRM)率为(18.9 ±9.0)%.单因素分析结果显示移植后OS较低与选用PBSCT、发生aGVHD、回输CD34+细胞数量≤2.5×106/kg、移植前输注红细胞＞30 U及移植后发生IFI显著相关(P值分别为0.034、0.001、0.006、0.000和0.001);移植后发生aGVHD与供受者ABO血型不同、移植前输注血小板＞100 U、输注红细胞＞30 U、回输CD34+细胞数量≤2.5×106/kg显著相关(P值分别为0.019、0.038、0.005和0.005);GR的发生与移植前输注血小板＞100 U显著相关(P=0.038).结论 MSD allo-HSCT治疗SAA疗效显著.减少移植前输血量、采用骨髓移植、增加回输CD34+细胞数量、有效防治aGVHD及移植后IFI对于提高疗效至关重要.
目的 評價人組織相容性抗原(HLA)匹配同胞供者異基因造血榦細胞移植(MSD allo-HSCT)治療重型再生障礙性貧血(SAA)的療效.方法 迴顧性分析2003年5月至2011年5月接受MSD allo-HSCT治療的41例SAA患者臨床資料.男24例、女17例,中位年齡23(5～41)歲.SAA-Ⅰ型患者28例,SAA-Ⅱ型9例,肝炎後再生障礙性貧血4例.異基因骨髓移植(allo-BMT)17例,異基因外週血榦細胞移植(allo-PBSCT)24例.預處理方案:環燐酰胺(CY)+抗人胸腺細胞毬蛋白(ATG)+氟達拉濱(Flu) 20例,CY+ATG+ Flu+阿糖胞苷(Ara-C)±白消安(Bu)或馬法蘭(Mel)21例.移植物抗宿主病(GVHD)預防方案:環孢素(CsA)加短療程甲氨蝶呤(MTX)25例,他剋莫司(FK506) 加短療程甲氨蝶呤(MTX)16例.迴輸CD34+細胞中位數:allo-BMT組患者3.48(2.39～4.80)×106/kg,allo-PBSCT組患者2.95(1.27～5.98)×106/kg.結果 41例患者移植後均穫得造血重建,中性粒細胞(ANC)恢複至≥0.5×109/L的中位時間為移植後14(10～23)d,PLT恢複至≥20×109/L的中位時間為移植後 19(8～38)d.12例(29.3%)患者髮生急性GVHD(aGVHD),其中Ⅰ～Ⅱ度11例、Ⅳ度1例.2例患者髮生慢性GVHD(cGVHD),跼限型與廣汎型cGVHD各 1例.4例(9.8%)患者齣現移植排斥(GR),行供者外週血榦細胞輸註後均恢複造血併存活.41例患者中死亡5例(12.2%):1例死于廣汎型cGVHD、4例死于侵襲性真菌感染(IFI).中位隨訪23(3～79)箇月,36例患者生存,預期5年總體生存(OS)率為(81.1±9.0)%、無病生存(DFS)率為(68.4±11.0)%、移植相關死亡(TRM)率為(18.9 ±9.0)%.單因素分析結果顯示移植後OS較低與選用PBSCT、髮生aGVHD、迴輸CD34+細胞數量≤2.5×106/kg、移植前輸註紅細胞＞30 U及移植後髮生IFI顯著相關(P值分彆為0.034、0.001、0.006、0.000和0.001);移植後髮生aGVHD與供受者ABO血型不同、移植前輸註血小闆＞100 U、輸註紅細胞＞30 U、迴輸CD34+細胞數量≤2.5×106/kg顯著相關(P值分彆為0.019、0.038、0.005和0.005);GR的髮生與移植前輸註血小闆＞100 U顯著相關(P=0.038).結論 MSD allo-HSCT治療SAA療效顯著.減少移植前輸血量、採用骨髓移植、增加迴輸CD34+細胞數量、有效防治aGVHD及移植後IFI對于提高療效至關重要.
목적 평개인조직상용성항원(HLA)필배동포공자이기인조혈간세포이식(MSD allo-HSCT)치료중형재생장애성빈혈(SAA)적료효.방법 회고성분석2003년5월지2011년5월접수MSD allo-HSCT치료적41례SAA환자림상자료.남24례、녀17례,중위년령23(5～41)세.SAA-Ⅰ형환자28례,SAA-Ⅱ형9례,간염후재생장애성빈혈4례.이기인골수이식(allo-BMT)17례,이기인외주혈간세포이식(allo-PBSCT)24례.예처리방안:배린선알(CY)+항인흉선세포구단백(ATG)+불체랍빈(Flu) 20례,CY+ATG+ Flu+아당포감(Ara-C)±백소안(Bu)혹마법란(Mel)21례.이식물항숙주병(GVHD)예방방안:배포소(CsA)가단료정갑안접령(MTX)25례,타극막사(FK506) 가단료정갑안접령(MTX)16례.회수CD34+세포중위수:allo-BMT조환자3.48(2.39～4.80)×106/kg,allo-PBSCT조환자2.95(1.27～5.98)×106/kg.결과 41례환자이식후균획득조혈중건,중성립세포(ANC)회복지≥0.5×109/L적중위시간위이식후14(10～23)d,PLT회복지≥20×109/L적중위시간위이식후 19(8～38)d.12례(29.3%)환자발생급성GVHD(aGVHD),기중Ⅰ～Ⅱ도11례、Ⅳ도1례.2례환자발생만성GVHD(cGVHD),국한형여엄범형cGVHD각 1례.4례(9.8%)환자출현이식배척(GR),행공자외주혈간세포수주후균회복조혈병존활.41례환자중사망5례(12.2%):1례사우엄범형cGVHD、4례사우침습성진균감염(IFI).중위수방23(3～79)개월,36례환자생존,예기5년총체생존(OS)솔위(81.1±9.0)%、무병생존(DFS)솔위(68.4±11.0)%、이식상관사망(TRM)솔위(18.9 ±9.0)%.단인소분석결과현시이식후OS교저여선용PBSCT、발생aGVHD、회수CD34+세포수량≤2.5×106/kg、이식전수주홍세포＞30 U급이식후발생IFI현저상관(P치분별위0.034、0.001、0.006、0.000화0.001);이식후발생aGVHD여공수자ABO혈형불동、이식전수주혈소판＞100 U、수주홍세포＞30 U、회수CD34+세포수량≤2.5×106/kg현저상관(P치분별위0.019、0.038、0.005화0.005);GR적발생여이식전수주혈소판＞100 U현저상관(P=0.038).결론 MSD allo-HSCT치료SAA료효현저.감소이식전수혈량、채용골수이식、증가회수CD34+세포수량、유효방치aGVHD급이식후IFI대우제고료효지관중요.
Objective To evaluate the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donor(MSD allo-HSCT) for severe aplastic anemia (SAA). Methods The clinical data of 41 SAA patients received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively. 24 patients were male, 17 were female. Median age was 23(5-43)years old. 28 patients had SAA-Ⅰ,9 had SAA-Ⅱ, and 4 had post-hepatitis aplastic anemia. 17 patients received allogeneic bone marrow(BM) transplantation(allo-BMT), and 24 received allogeneic peripheral blood stem cell(PBSC) transplantation (allo-PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY)+ anti-thymocyte globulin(ATG)+ fludarabine(Flu), 21 received CY+ATG+Flu+ cytarabine(Ara-C)±busulfan (Bu)/melphalan(Mel). Prophylaxis for graft-versus-host disease(GVHD): 25 paitents received cyclosporine(CSA) plus short-term methotrexate(MTX), 16 received tacrolimus (FK506) plus short-term MTX. The median number of infused CD34+ cells were 3.48(2.39-4.80)×106/kg in allo-BMT and 2.95(1.27-5.98)×106/kg in allo-PBSCT, respectively. Results Hematopoietic reconstitution was observed in all 41 patients(100%).The median time of neutrophils(ANC) reached to 0.5×109/L and platelets( PLT) reached to 20×109/L were 14(10-23)days and 19(8-38)days,respectively. 12 patients developed acute GVHD (aGVHD), out of which 11 developed grade Ⅰ-Ⅱ aGVHD,and one developed grade Ⅳ. 2 patients occurred chronic GVHD(cGVHD), out of which one with local cGVHD and the other with extensive. 4 patients occurred graft rejection(GR), all of them recovered haemopoiesis and survived after donor PBSC infusion. 5 patients(12.2%) died, out of which one died of extensive cGVHD, and 4 died of invasive fungal infections(IFI). Median follow-up time was 23(3-79) months. 36 patients survived. 5-year estimated overall survival(OS), disease free survival(DFS), and transplant-related mortality (TRM) was (81.1±9.0)%, (68.4±11.0)%, and (18.9±9.0)%, respectively. Univariate analysis showed that lover OS had significant correlation with receiving PBSCT, occurrence of aGVHD, the number of infused CD34+ cells no more than 2.5×106/kg , the number of red blood cell(RBC) transfusion before transplant more than 30 U and occurrence of IFI after transplantation(P=0.034, 0.001, 0.006, 0.000, 0.001, respectively). Occurrence of aGVHD had significant correlation with the disparity between donor and recipient ABO blood groups, the number of PLT transfusion more than 100 U, and the number of RBC transfusion more than 30 U before transplantation, the number of infused CD34+ cells no more than 2.5×106/kg(P=0.019, 0.038, 0.005, 0.005, respectively). The occurrance of GR had significant correlation with the number of PLT transfusion more than 100 U before transplantation(P=0.038). Conclusion MSD allo-HSCT is an effective therapy for patients with SAA. Lower number of blood transfusion before transplantation, use of BMT, more number of infused CD34+ cells can effectively prevent and treat aGVHD and IFI after transplantation, which may improve the efficacy of MSD allo-HSCT for SAA.
