CAJ | 학술논문

目的分析无关供者造血干细胞移植(HSCT)联合伊马替尼治疗Ph+急性淋巴细胞白血病(Ph+ ALL)的预后及其影响因素.方法 2002年2月至2012年2月间,25例行无关供者HSCT的Ph+-ALL患者纳入研究,其中移植前处于第1次完全缓解(CR1)期18例,≥第2次完全缓解(CR2)期7例;BCR/ABL融合基因为Major BCR/ABL型(M型)9例,minor BCR/ABL型(m型)16例.移植前均给予伊马替尼治疗.术后采用环孢素A、甲氨蝶呤、吗替麦考酚酯及抗胸腺细胞球蛋白预防移植物抗宿主病(GVHD).结果中位随访时间为20.5个月,HSCT后中性粒细胞和血小板植活的中位时间分别是12 d(10～20d)及12.5 d(10～36 d).移植后30 d所有患者均为完全供者嵌合型.2年的总体存活率(OS)和无白血病存活率(LFS)分别为(55.3+ 10.9)％和(49.1+12.2)％,2年的累计复发率(RI)和急性GVHD的累计发生率分别为(29.6+9.4)％和(48.0+10.6)％.单因素分析提示,CR1的患者OS明显高于非CR1患者(77.1％和20％,P=0.028),LFS也高于非CR1患者(74.1％和0,P=0.030);BCR/ABL融合基因M型的患者OS比m型患者低(22.2％和80.2％,P=0.010);LFS也比m型患者低(13.9％和78.3％,P=0.015);而年龄、性别、初诊白细胞数、预处理方案、干细胞来源、HLA相合情况、急性GVHD等对生存无明显影响.多因素分析提示,移植前缓解状态及BCR/ABL融合基因类型是OS的危险因素[P=0.038,Exp(B)=3.823;P=0.023,Exp(B)=4.829].结论移植前缓解状态及BCR/ABL融合基因类型是影响无关供者HSCT预后的主要因素,患者处于CR1期进行移植获得的效果更佳,应密切监测融合基因M型患者移植后状态.
목적 분석무관공자조혈간세포이식(HSCT)연합이마체니치료Ph+급성림파세포백혈병(Ph+ ALL)적예후급기영향인소.방법 2002년2월지2012년2월간,25례행무관공자HSCT적Ph+-ALL환자납입연구,기중이식전처우제1차완전완해(CR1)기18례,≥제2차완전완해(CR2)기7례;BCR/ABL융합기인위Major BCR/ABL형(M형)9례,minor BCR/ABL형(m형)16례.이식전균급여이마체니치료.술후채용배포소A、갑안접령、마체맥고분지급항흉선세포구단백예방이식물항숙주병(GVHD).결과 중위수방시간위20.5개월,HSCT후중성립세포화혈소판식활적중위시간분별시12 d(10～20d)급12.5 d(10～36 d).이식후30 d소유환자균위완전공자감합형.2년적총체존활솔(OS)화무백혈병존활솔(LFS)분별위(55.3+ 10.9)％화(49.1+12.2)％,2년적루계복발솔(RI)화급성GVHD적루계발생솔분별위(29.6+9.4)％화(48.0+10.6)％.단인소분석제시,CR1적환자OS명현고우비CR1환자(77.1％화20％,P=0.028),LFS야고우비CR1환자(74.1％화0,P=0.030);BCR/ABL융합기인M형적환자OS비m형환자저(22.2％화80.2％,P=0.010);LFS야비m형환자저(13.9％화78.3％,P=0.015);이년령、성별、초진백세포수、예처리방안、간세포래원、HLA상합정황、급성GVHD등대생존무명현영향.다인소분석제시,이식전완해상태급BCR/ABL융합기인류형시OS적위험인소[P=0.038,Exp(B)=3.823;P=0.023,Exp(B)=4.829].결론 이식전완해상태급BCR/ABL융합기인류형시영향무관공자HSCT예후적주요인소,환자처우CR1기진행이식획득적효과경가,응밀절감측융합기인M형환자이식후상태.
Objective To analyze prognostic factors for the clinical outcome of unrelated donor hematopoietic stem cell transplantation (URD-HSCT) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) following imatinil-based therapy.Method From February 2002 to February 2012,25 patients with Ph+ ALL receiving URD-HSCT were enrolled in the study.There were 17 cases in the first CR (CR1),and 8 cases beyond CR2.Nine patients expressed major BCR/ABL (M) and 16 expressed minor BCR/ABL (m).All the patients were administrated with imatinib before transplantation.Graft versus host disease (GVHD) prophylaxis protocol included cyclosporine A (CSA),short term methotrexate (MTX),antithymocyte globulin (ATG) and mycophenolate mofetil (MMF).Results The median time of ANC ≥0.5 × 109/L was 12 (10-20) days,and that of PLT ≥20× 109/L was 12 (10-36) days.Thirty days after URD-HSCT,all patients achieved full donor chimerism.The median follow-up duration post-transplantation was 20.5 (3 to 93) months.The 2-year overall survival (OS) and leukemia-free survival (LFS) was (55.3 ± 10.9) ％ and (49.1 ± 12.2) ％,respectively.The cumulative incidence of relapse and aGVHD was (29.6 ± 9.4) ％ and (48.0-± 10.6) ％,respectively.The uninvariate analysis revealed that the OS and LFS were higher in CR1 group pre-HSCT than in non-CR1 group (77.1％ vs.20％,P =0.028;74.1％ vs.0,P=0.030),lower in major BCR/ABL than in minor BCR/ABL group (22.2％ vs.80.2％,P=0.010; 13.9％ vs.78.3％,P =0.015).The median age at HSCT,gender,WBC at diagnosis,conditioning regimen,stem-cell source and HLA typing didn't significantly influence the outcome of URD-HSCT.The multivariate analysis revealed that both the status of disease Pre-HSCT and BCR/ABL subtype were the unfavorable factors for OS [P=0.038,Exp(B) =3.823; P =0.023,Exp(B) =4.829].Conclusion The status of disease Pre-HSCT and BCR/ABL subtype were the major prognostic factors.The outcome of URD-HSCT done in CR1 was desirable and we should pay more attention to monitoring in the minor BCR/ABL patients after URD-HSCT.