成年人E2A-PBX1融合基因阳性急性B淋巴细胞白血病临床特征及预后分析  

Clinical characteristics and prognosis analysis of adult B-cell acute lymphoblastic leukemia with E2A-PBX1 fusion gene positive

作　　者：黎秋丽 林岱楠 高雅[1] 王蔷[1] 蒋玲[1] 宣丽[1] 周璇[1] 刘晓力[1] 刘启发[1] 周红升[1] Li Qiuli;Lin Dainan;Gao Ya;Wang Qiang;Jiang Ling;Xuan Li;Zhou Xuan;Liu Xiaoli;Liu Qifa;Zhou Hongsheng(Department of Hematology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学南方医院血液科,广州510515

出　　处：《白血病．淋巴瘤》2019年第10期582-587,共6页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金(81770170);广东省自然科学基金(2017A030313601);广东省科技计划(2016A020215112);南方医科大学临床研究重点项目(LC2016ZD009)。

摘　　要：目的探讨成年人E2A-PBX1融合基因阳性急性B淋巴细胞白血病(B-ALL)的临床特征。方法收集2015年3月至2017年12月就诊于南方医科大学南方医院并接受规律化疗的91例费城染色体阴性B-ALL患者的临床资料,根据融合基因检测结果将患者分为E2A-PBX1融合基因阳性组与E2A-PBX1融合基因阴性组,回顾性分析两组患者的临床特征及预后。将E2A-PBX1融合基因阴性组进一步细分为MLL-AF4融合基因阳性组、其他ALL组,与E2A-PBX1融合基因阳性组进行预后比较。结果E2A-PBX1融合基因阳性ALL患者11例,E2A-PBX1融合基因阴性ALL患者80例。E2A-PBX1融合基因阳性组仅乳酸脱氢酶(LDH)水平高于E2A-PBX1融合基因阴性组[4063 U/L(1070~9554 U/L)比454 U/L(103~18651 U/L)],U=-4.700,P<0.01),年龄、性别、白细胞计数、髓外侵犯差异均无统计学意义(均P>0.05);E2A-PBX1融合基因阳性患者均为普通B细胞表型,其中应用流式细胞术检测费城染色体样ALL表型CRLF2、pCRKL、pSTAT5表达量的7例患者中,4例有不同程度表达。E2A-PBX1融合基因阳性组11例中首个疗程诱导化疗后完全缓解(CR)9例,微小残留病(MRD)转阴7例,复发8例;E2A-PBX1融合基因阴性组80例中,首个疗程诱导化疗后CR、MRD转阴、复发分别有71、53、26例,两组间首个疗程诱导化疗后CR、MRD转阴差异均无统计学意义(P=0.721,P=0.487),复发差异有统计学意义(χ^2=7.751,P=0.012)。中位随访17个月(1~44个月),E2A-PBX1融合基因阳性组1年总生存(OS)率与1年无事件生存(EFS)率均低于阴性组(43.6%比70.0%,P=0.020;13.6%比60.0%,P=0.002);亚组分析显示,E2A-PBX1融合基因阳性组与MLL-AF4融合基因阳性组的1年OS率及1年EFS率差异均无统计学意义(P=0.617,P=0.984)。结论在成年人B-ALL中,E2A-PBX1融合基因阳性率低,早期治疗反应好,但累积复发率高,应与MLL基因重排ALL一样归入遗传学高危组,并需进一步探索新的治疗策略。Objective To investigate the clinical features of adult B-cell acute lymphoblastic leukemia(B-ALL)with E2A-PBX1 fusion gene positive.Methods The clinical data of 91 Philadelphia chromosome negative B-ALL patients who received chemotherapy regularly in Nanfang Hospital of Southern Medical University from March 2015 to December 2017 were collected.According to the fusion gene detection results,the patients were divided into E2A-PBX1 fusion gene positive group and E2A-PBX1 fusion gene negative group.The clinical features and prognosis of both groups were retrospectively analyzed.And then E2A-PBX1 fusion gene negative group was further divided into MLL-AF4 fusion gene positive group and the other ALL groups,which were compared with E2A-PBX1 fusion gene positive group in the prognosis.Results There were 11 ALL patients with E2A-PBX1 fusion gene positive,and 80 ALL patients with E2A-PBX1 fusion gene negative.The level of lactic dehydrogenase(LDH)in E2A-PBX1 fusion gene positive group was higher than that in E2A-PBX1 fusion gene negative group[4063 U/L(1070-9554 U/L)vs.454 U/L(103-18651 U/L),U=-4.700,P<0.01],and there were no statistically significant differences in age,gender,white blood cell count and extramedullary invasion(all P>0.05).The immunophenotypes of ALL patients with E2A-PBX1 fusion gene positive were all common B-cell phenotype.Out 4 of 7 ALL patients showed the different expression of Philadelphia-like ALL phenotype CRLF2 or phosphorylated CRKL or phosphorylated STAT5 by using flow cytometry.The complete remission(CR),minimal residual disease(MRD)-negative and the recurrence for 11 cases of E2A-PBX1 fusion gene positive group included 9,7,8 cases,respectively after first course of induction chemotherapy.The CR,MRD-negative and the recurrence for 80 cases of E2A-PBX1 fusion gene negative group included 71,53,26 cases,respectively after the first course of induction chemotherapy.There were no statistically significant differences in the CR and MRD-negative between the two groups after the first course of in

关 键 词：白血病 B细胞 成年人 E2A-PBX1融合基因 复发 生存率 

分 类 号：R73[医药卫生—肿瘤]