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[4 063 U／L(1 070～9 554 U／L)比454 U／L(103～18 651 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(χ2＝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.

abstractsObjective 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 [4 063 U/L (1 070 - 9 554 U/L) vs. 454 U/L (103 -18 651 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 induction chemotherapy (P ＝ 0.721, P ＝ 0.487), but there was a statistical difference in the recurrence (χ2 ＝ 7.751, P ＝ 0.012). The median follow-up time was 17 months (1-44 months), and the 1-year overall survival (OS) rate and 1-year event-free survival (EFS) rate of E2A-PBX1 fusion gene positive ALL group were lower than those of the negative group (OS: 43.6% vs. 70.0%, P ＝0.020;EFS: 13.6% vs. 60.0%, P ＝ 0.002). Subgroup analysis showed that there were no statistical differences between E2A-PBX1 fusion gene positive group and MLL-AF4 fusion gene positive group in 1-year OS rate and 1-year EFS rate (P ＝ 0.617, P ＝ 0.984). Conclusions E2A-PBX1 fusion gene positive rate is low in adult B-ALL patients with a good response to traditional chemotherapy in the early stage, but its cumulative recurrence rate is high. It is a high-risk cytogenetic abnormality which is similar to MLL gene rearrangement and needs to explore novel therapy strategies.