急性髓系白血病细胞遗传学特征及不同剂量柔红霉素DA方案化疗效果分析

Cytogenetic characteristics of acute myeloid leukemia and effect of DA regimen with different doses of daunorubicin

目的 分析急性髓系白血病（AML）（非M3型）染色体及相关融合基因的遗传学特征,评估其采用不同剂量柔红霉素及标准剂量阿糖胞苷组成的DA方案化疗的预后.方法 收集2013年1月至2015年1月确诊的56例初治AML（非M3型）患者,采用短期培养法处理骨髓样本,用R显带核型分析进行细胞遗传学检测,并应用反转录聚合酶链反应（RT-PCR）和10%聚丙烯酰胺凝胶电泳对标本进行31种融合基因分型检测.接受DA方案诱导治疗时按照不同柔红霉素剂量将患者分为3组（减低剂量组、标准剂量组、大剂量组）,观察3组患者治疗后完全缓解（CR）率及生存期,并采用χ2检验分析细胞遗传学和分子生物学异常对3组患者化疗效果及总生存（OS）率的影响.结果 56例患者中染色体核型异常18例（32.1%）,其中染色体数目异常6例（10.7%）,结构异常16例（28.6%）,同时有数目和结构异常4例（7.1%）.最常见的结构异常为t（8;21）,数目异常为＋8、-Y.融合基因检出率为48.2%（27/56）,其中AML1-ETO 13例,CBFβ-MYH114例,AML1-MDS13例.融合基因和染色体核型分析使AML患者的遗传学异常检出率提升至62.0%.采用DA方案诱导化疗的总CR率为73.2%,2年OS率为42.9%.标准剂量组中中危患者的化疗缓解率低于低危患者（χ2=8.976,P=0.002）;低危患者中减低剂量组与标准剂量组的化疗缓解率差异无统计学意义（P〉0.05）,但标准剂量组2年OS率有优势（χ2=8.045,P=0.005）.结论 成年人AML具有独特的细胞遗传学特征,可辅助指导临床诊断、分型及预后判断.中危患者的预后差于低危患者,低危患者采取减低剂量DA方案也可获得较好的化疗缓解率,但标准剂量DA方案在长期生存方面优势显著.

Objective To analyze the genetic characteristics of chromosomes and related fusion genes in acute myeloid leukemia （AML） （non-M3）, and to evaluate the prognosis of patients with chemotherapy of DA regimen with different doses of daunorubicin. Methods Fifty-six patients with newly diagnosed non-M3 AML from January 2013 to January 2015 were collected. Adopted short-term culture method was used to treat bone marrow, R-binding chromosome karyotyping was used to detect cytogenetic. Thirty-one types of fusion gene were identified by PCR and 10 % agarose gel electrophoresis. All patients treated by DA regimen were divided into group A, group B and group C according to different dosage of daunorubicin. Then, complete remission （CR） rate and survival time in the 3 groups were observed. The effect of cytogenetic and molecular biology abnormality on the chemotherapy, CR rate and overall survival （OS） of the 3 groups were analyzed by the chi-square test. Results Among the 56 patients, 18 cases （32.1%） had abnormal chromosome karyotype, 6 cases （10.7 %） had abnormal number of chromosome, 16 cases （28.6 %） had abnormal structure of chromosome, and 4 cases （7.1 %） had both abnormal number and structure of chromosome. Meanwhile, the most common abnormal structure was t（8;21）, and the most common abnormal quantity were＋8, -Y. Detective rate of genetic abnormality was raised to 62.00 % through fusion gene and chromosome karyotype analysis. The total CR rate of DA-induced chemotherapeutic regimen was 73.2 %, and the two-year OS rate was 42.9%. The remission rate of chemotherapy in the middle-risk group was significantly lower than that in the low-risk group （χ 2 = 8.976, P = 0.002）, but there was no significant difference between the low-dose chemotherapy group and the standard dose chemotherapy group （P〉0.05）. The standard dose group showed a significant advantage in the OS rate （χ2= 8.045, P= 0.005）. Conclusions Adult acute leukemia has its unique cytogenetic characteristics, which can assist in guiding clinical diagnosis, classification and prognosis. The prognosis of middle-risk patients is significantly lower than the low-risk group. Low-risk patients could benefit from a reduced dose of DA regimen, but the standard dose DA regimen has a significant advantage in long-term survival.