伴EVI1高表达的中高危急性髓系白血病临床特点及早期治疗效果

目的：探讨EVI1基因阳性的急性髓系白血病（acute myeloid leukemia, AML）患者的临床生物学特点及其对早期化疗疗效的影响。方法： 选择2015年3月至2016年7月在北京大学血液病研究所诊治的361例AML患者病例资料进行回顾性分析，其中33例AML患者EVI1基因阳性，分析比较其临床特征和生物学特征，并比较中危及高危伴EVI1+AML患者的临床与生物学特征及诱导缓解率，分析获得完全缓解（complete remission， CR）的影响因素。32例健康供者进行EVI1/ABL基因水平检测，确定EVI1表达的异常界值。结果：以EVI1/ABL基因定量表达≥8.0%作为EVI1的阳性表达。在361例初发AML中，EVI1+AML患者共33例（9.1%），其中男性16例，女性17例，中位年龄45（18~67）岁，中位随访期为6.6（0.7~13.2）个月。中危核型17例，包括正常核型9例，1例+8；高危核型14例，包括7例-7/7q-，4例t(v;11q23)，3例inv(3)/t(3;3)，2例未见分裂象。33例患者1个疗程完全缓解率为42.4%，总CR率为60.6%。按《美国国立综合癌症网络（National Comprehensive Cancer Network，NCCN ）指南》预后分层，分为中危组16例，高危组17例，无低危组患者。中危组与高危组1个疗程CR率分别为68.8%和17.6%（P=0.005）， 总CR率分别为81.3%和41.2%（P=0.032）,复发率为7.7%和14.3%。单因素分析，高危染色体核型对1个疗程CR率及总体CR率均有影响（P=0.004、0.029）。高危组患者病死率显著高于中危组（41.2% vs. 6.3%，P=0.039）， 且总生存（overall survival, OS）显著低于中危组（P=0.012）。结论: EVI1基因在AML中常伴中、高危核型表达，对于AML患者来说可能不是独立的预后因素，伴-7/7q-、t(v;11q23)及inv(3)/t(3;3)等高危染色体核型的预后差，其1个疗程CR率及总CR率、长期生存率低，病死率高，应尽早行异基因造血干细胞移植。

Clinical features and early treatment effects in intermediate risk and poor risk acute myeloid leukemia with EVI1 positive

Objective:To investigate the clinical biological characteristics of EVI1 positive acute myeloid leukemia (AML) and its effect on early chemotherapy.Methods:The clinical and biological characteristics of 33 AML patients with EVI1 positive were retrospectively analyzed in 361 AML patients who were diagnosed and treated in our institute from March 2015 to July 2016,and the clinical and biological features,and rates of the induced remission were compared between the intermediate risk and poor risk with EVI1 positive AML,moreover,the influential factors on complete remission (CR) were analyzed.The expression of EVI1/ABL was tested in 32 healthy donors to confirm the abnormal threshold of EVI1 expression.Results:The definition of EVI1 positive was that the quantitative expression of EVI1/ABL was more than 8.0％.The 33 AML patients with EVI1 positive were found in 361 newly diagnosed AML patients,in which the female and male patients were 17 and 16 respectively,the median age was 45 (18-67) years,with a median follow-up of 6.6 (0.7-13.2) months.Intermediate karyotype was found in 17 patients (including 9 patients with normal karyotypes,1 patient with + 8);unfavorable karyotype was found in 14 patients [including 7 patients with-7/7q-,4 patients with t (v;11q23),3 patients with inv (3)/t (3;3),and 2 patients without mitotic figures].The rate of CR in the first induction chemotherapy was 42.4％,and the rate of total CR was 60.6％.According to the NCCN,16 intermediate risk patients and poor risk patients were divided,without favorable risk patients.The rate of CR in the first induction chemotherapy were 68.8％ and 17.6％ (P =0.005) in the intermediate risk and poor risk respectively,that of total CR were 81.3％ and 41.2％ (P =0.032),and the rates of relapse were 7.7％ and 14.3％.Univariable analysis revealed that unfavorable karyotype could affect the rate of CR in the first reduction chemotherapy and that of total CR (P =0.004,0.029).The poor risk patients had higher mortality (41.2％ vs.6.3％,P =0.039) and lower overall survival (OS) (P =0.012).Conclusion:EVI1 may be not an independent prognostic factor for the AML patients considering the appearance in the intermediate and poor risk patients.It predicts poor outcome in the EVI1 positive AML patients who have unfavorable karyocytes,such as-7/7q-,t (v;11 q23),and inv (3)/t (3;3),and also a low rate of both CR in the first induction chemotherapy and total CR.It also has a low rate of long-term survival and high mortality in the AML patients with EVI1 positive,who may benefit from allogeneic bone marrow transplantation as soon as possible.