摘要
目的:评价异基因造血干细胞移植(allo-HSCT)治疗慢性粒细胞白血病(CML)的疗效,并分析影响CML长生存的预后因素。方法:118例CML患者包括慢性期88例、加速期8例、急变期22例,其中83例接受相关移植、35例无关移植。预处理方案:36例患者用全身照射(TBI)联合环磷酰胺联合(Cy)、82例改良BuCy(白消安、环磷酰胺和阿糖胞苷)。移植物抗宿主病(GVHD)预防:68例相关人类白细胞抗原(HLA)全相合移植用环孢素(CsA)和甲氨蝶呤(MTX),50例无关供者及相关1个以上位点不合者采用CsA、MTX、抗胸腺细胞球蛋白(ATG)或麦考酚酸酯(MMF)。Cox模型分析影响长生存的因素。结果:118例患者除3例死于预处理相关毒性(RRT)外其余均获造血重建。移植后5年累计感染发生率为42.6%,巨细胞病毒血症累计阳性率为41.6%。Ⅱ～Ⅳ度急性GVHD累计发生率为33.3%,其中相关全相合供者(MSD)和无关、相关不相合供者(MRD/URD)发生率分别为23.1%和46.9%(P=0.01);1年累计慢性GVHD发生率为47.8%,其中MSD和MRD/URD慢性GVHD发生率分别为51.4%和42.2%(P=0.260)。GVHD致死率为18.3%。移植后5年白血病累计复发率为17%,其中MSD和MRD/URD复发率分别为12.5%和23.9%%(P=0.228)。5年累计总生存(OS)和无病生存(DSF)率分别为69.5%和62.6%,其中MSD与MRD/URD的5年OS率和DSF率分别为78.5%比57.2%和72.7%比48.3%(P=0.018,P=0.017)。慢性期与加速/急变期的5年OS率和DSF率分别79.9%、36.7%和72.4%、32.6%(P<0.001)。多因素Cox模型分析显示,Ⅱ～Ⅳ度急性GVHD、HLA不相合、诊断至移植时间≥1年为OS的独立危险因素。加速期、急变期和三联、四联GVHD预防方案为影响DSF的独立危险因素。结论:影响CML-allo-HSCT长生存的主要因素是移植的时机、疾病状态、HLA相合程度和移植后GVHD。GVHD是移植后死亡的主要原因。
Objective To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation （allo-HSCT） for chronic myeloid leukemia （CML） and analyze the prognostic factors influencing the long term survival. Methods One hundred and eighteen CML patients with a median follow-up period of 41 months were enrolled, including 88 in chronic phase, 8 in accelerate phase and 22 with blast crisis, Eighty three patients received related donor allo-HSCT and 35 with unrelated donor allo-HSCT. Thirty six patients received total body irradiation and cyclophosphamide （Cy） as preconditioning regimen and 82 patients received modified BuCy （busulfan, Cy, cytosine arabinoside） protocal. For graft-versus-host disease （GVHD） prophylaxis, ciclosporine （CsA） and methotrexate （MTX） were used in patients receiving human leucocyte（HLA） fully matched sibling donor （MSD） transplants and CsA, MTX, antihuman thymocyte globulin （ATG） and mycophenolate （MMF） were used in patients receiving HLA not fully matched related donor （MRD） and unrelated donors （URD） transplants. Cox regression model was used to evaluate the prognostic factors of chronic myeloid leukemia （CML） and Kaplan and Meier survival analysis model was used to estimate the cumulative overall survival （OS） and the disease free survival （DFS）. Results Except the three cases died of preconditioning related toxicity, all others got hematopoitic reconstruction. Five years cumulative infection rate was 42.6%, CMV antigenemia was 41.6%. The cumulative incidence of Ⅱ-Ⅳ acute GVHD was 33.3%; 23.1% in MSD and 46.9% in MRD/URD （P=0.01）. One year cumulative incidence of chronic GVHD was 47.8%; 51.4% in MSD and 42.2% in MRD/URD, respectively （P=0.260）. The 5-year cumulative relapsing rate was 17%; 12.5% in MSD and 23.9% in MRD/URD （P=0.228）. Five years cumulative OS and DFS rates were 69.5% and 62.6%, respectively; 78.5% and 72.7% in MSD, 57.2% and 48.3% in MRD/URD, respectively （P=0.018, P= 0.017）. Five years OS
出处
《内科理论与实践》
2010年第1期39-43,共5页
Journal of Internal Medicine Concepts & Practice
基金
国家863计划(项目编号:2006AA02Z4A0)
国家自然科学基金(项目编号:30971300)
关键词
慢性粒细胞白血病
异基因造血干细胞移植
长期生存
Chronic myeloid leukemia
Stem cell transplantation
Graft-versus-host disease
Overall survival
