混合谱系白血病-AF6融合基因阳性急性髓系白血病八例临床特点与预后

Clinical characteristics and prognostic of 8 cases of acute myeloid leukemia patients with MLL-AF-6 fusion gene

目的 探讨混合谱系白血病（MLL）-AF6融合基因[t（6;11） （q27;q23）]阳性急性髓系白血病（AML）患者的临床特点与预后.方法 收集安徽省立医院血液内科住院初治MLL-AF6融合基因阳性的AML患者8例,利用多重巢式反转录-聚合酶链反应（RT-PCR）检测治疗前后MLL-AF6融合基因动态变化,分析患者临床特征、免疫表型、细胞遗传学、患者首次诱导治疗后完全缓解（CR）率、总体生存率、造血干细胞移植效果与患者预后的关系.结果 2009年2月至2013年8月住院患者确诊为急性白血病（AL）患者472例,其中AML患者285例,包括MLL-AF6融合基因阳性AML患者8例,占AL的1.69％（8/472）,占AML的2.80％（8/285）.MLL-AF6融合基因阳性AML患者按WHO分型：M11例,M22例,M42例,M53例,以M4/M5为主（5例）.8例AML患者首次化疗后CR 5例,总体生存4例.4例单纯化疗患者中,有2例在第1个疗程结束后MLL-AF6融合基因转阴,且1例获得了血液学CR并已生存26个月,1例初诊后6个月复发,后经治疗后死亡;2例患者第1个疗程结束后MLL-AF6融合基因未转阴（1例转为弱阳性,1例仍为阳性）,均未获得血液学CR且死亡.4例造血干细胞移植患者中,3例移植前MLL-AF6融合基因转阴,均无复发,仍生存,平均生存时间28个月;1例患者移植前MLL-AF6融合基因未转阴（弱阳性）,移植后复发死亡.结论 MLL-AF6融合基因阳性AML患者在AML-M4/M5中发生率高,发病时常伴有高白细胞、器官浸润,且治疗效果差,易复发,预后差,造血干细胞移植可显著改善患者预后.RT-PCR检测治疗前后MLL-AF6融合基因的动态变化可在一定程度上帮助判断患者预后.

Objective To investigate the clinical characteristics and prognostic of acute myeloid leukemia （AML） patients with MLL-AF-6 fusion gene.Methods Samples from eight acute myeloid leukemia patients with MLL-AF-6 fusion gene hospitalized in Department of Hematology of Anhui Provincial Hospital were collected.The correlation between clinical features,immunophenotype,rate of complete remission after the first induction therapy,overall survival,response to allo-HSCT or prognosis of patients and the dynamic change of MLL-AF6 fusion gene which was accessed by multiplex nested reverse transcription-polymerase chain reaction was.Results From February 2009 to August 2013,472 patients were diagnosed as acute leukemia （AL）,including 285 AML patients,and eight of them with MLL-AF-6 fusion gene,who were account for 1.69 % （8/472） of AL and 2.80 % （8/285） of AML.According to WHO classification,all MLL-AF6 fusion gene-positive patients were classified into M1 （1 case）,M2 （2 cases）,M4 （2 cases）,M5 （3 cases）,in which M4/M5 were accounted for 62.50 % （5/8）.After first induction therapy,the complete response （CR） and overall survival （OS） rated of AML patients with MLL-AF6 were 62.50 % （5/8） and 50.0 % （4/8）,respectively.At the end of first course therpy,two of four patients receiving chemotherapy alone had negative detection of MLL-AF-6 fusion gene.During the follow-up period,one of them achieved hematologic complete remission and survived for 26 months,and the other had recurrence six months after diagnosis and died after treatment.The other 2 patients receiving chemotherapy alone had no change in MLL-AF6 fusion gene expression,who didn ＇t achieve hematologic complete remission and died finally.Four patients received bone marrow transplantation at the end of first course.Three of them became MLL-AF6 fusion gene negative and achieved hematologic complete remission,and survived with mean survival 28 months.One patient who received bone marrow transplantation did not become MLL-AF6 fusion gene negative and died after transplantation.Conclusions There is high incidence of MLL-AF6 fusion gene rearrangement in M4/M5 patients,which is often accompanied with hyperleukocytosis,organ infiltration,worse therapeutic effects,high recurrence rate and poor prognosis.HSCT is a reasonable treatment to improve the prognosis of those patients.Monitor the changes of MLL-AF6 fusion gene during the treatment can help to indicate the prognosis of patients.