Ph染色体／BCR-ABL基因阳性急性髓系白血病15例临床和实验室特征分析

Clinical and laboratorial characteristics analysis on 15 cases of acute myeloid leukemia with Phchromosome and BCR-ABL gene positive

目的 探讨Ph染色体和（或）BCR-ABL融合基因阳性急性髓系白血病（AML）患者的临床和实验室特征.方法 收集15例初治Ph染色体/BCR-ABL基因阳性急性髓系白血病（Ph/BCR-ABL＋AML）患者的临床资料,对其细胞形态学、细胞遗传学和细胞免疫表型检测、临床特征及预后进行回顾性分析.结果 Ph＋AML在同时期AML中检出率为1.47％（15/1018）,其中男8例,女7例,中位发病年龄38岁,白细胞计数（WBC）中位数为38×10^9/L;髓外浸润6例（40％）;FAB分型M28例（53.3％）,M44例（26.7％）.15例患者均表达髓系细胞抗原,且均表达CD34,其中3例伴有淋系抗原表达.初诊时均可检测到Ph染色体,3例（20％）伴有附加染色体异常.15例均可检测到BCR-ABL融合基因阳性,P190BCR-ABL 4例（26.7％）,P210BCR-ABL 11例（73.3％）,1例同时伴有CBFβ-MYH11的表达.8例患者行AML基因突变检测,4例存在AML基因突变.15例患者中9例经诱导治疗1个疗程后获完全缓解（CR）,化疗联合酪氨酸激酶抑制剂（TKI）组的CR率（85.7％）优于单独化疗组（37.5％）,但差异未见统计学意义（P=0.12）.化疗联合TKI组中位生存期（13个月）及化疗联合造血干细胞移植（HSCT）组（60个月）均优于单纯化疗组（8个月）,P=0.0064、0.0400,至随访结束,化疗联合TKI及HSCT组患者均存活.结论 Ph染色体阳性AML在临床特征、细胞免疫表型、形态学方面有其特殊性,常规筛查BCR-ABL融合基因、AML常见突变基因、染色体为初治白血病诊断提供了更多依据.此类白血病疗效差、生存期短,化疗同时联合TKI完全缓解后尽早行异基因造血干细胞移植,能有效改善预后.

Objective To investigate the clinical and laboratory characteristics of patients with Ph chromosome/BCR-ABL gene-positive acute myeloid leukemia (Ph/BCR-ABL ＋ AML). Methods The clinical date of 15 primary patients with Ph/BCR-ABL ＋ AML were collected to retrospec-tively analyze the cell morphology, cytogenetics and cellular immunophenotyping, chnical features and prognosis. Results The detection rate of Ph ＋AML patients among AML in the same period was 1.47% （15/1 018）. The results showed that 15 patients （8 males and 7 females） were diagnosed as Ph/BCR-ABL＋AML, whose median age was 38 years old and median white blood cell count was 38 x 10^9/L; 6 cases （40%） were extramedullary infiltration; according to French-American-Britain classification style, there were 8 cases of M2 （53.3%） and 4 cases of M4 （26. 7%). Immnologic analysis showed that 15 Ph＋ AML patients expressed myeloid antigens and CD34, of which 3 cases were immunophenotyped with myeloid and lymphoid cell antigens. In the initial diagnosis Ph positive chromosome can be detected in the 15 patients, and some chromosomes were associated with additional chromosomal abnormalities in 3 cases. BCR-ABL fusion gene transcript positive were detected in all cases, with P19OBCR-ABL in 4 ca-ses （26. 7%), P210BCR-ABL in 11 cases （73.3%）, among which 1 case coexpressed CBF＋-MYHll.Four out of 8 cases had AML-like gene mutations. Nine of 15 patients were completely relieved after one course of induction therapy. The complete remission （CR） rate （85.7%） in chemotherapy combined with tyrosine kinase inhibitor （TKI） group was better than that in signle chemotherapy group （37.5%）, but the difference was not statistically significant (P = 0. 12). Median survival time of chemotherapy combined with TKI group （13 months） and chemotherapy combined with hematopoietic stem cell trans-plantation （HSCT） group （60 months) were both better than that of single chemotherapy group （8 months）, P=0. 0064, 0. 0400. At the end of the follow-up, all patients in chemotherapy combined with TKI group and HSCT groups survived. Conclusions There are special characteristics in the clinical symptoms, cellular immune phenotypes and morphology of Ph/BCR-ABL ＋ AML. Routine screening of BCR-ABL fusion gene, AML common mutant gene and the chromosome provides more evidence for early diagnosis of leukemia. Efficacy on Ph/BCR-ABL ~ AML is poor and survival time is short, but implement allogeneic hematopoietic stem cell transplantation after chemotherapy combined with TKI could improve prognosis.