59例BCR/ABL阳性急性淋巴细胞白血病的临床特征及治疗转归

Clinical characteristics and outcomes of 59 patients with acute lymphoblastic leukemia positive for BCR/ABL

目的研究分析BCR/ABL阳性急性淋巴细胞白血病(BCR/ABL+-ALL)临床特征及治疗转归,筛选可能影响临床疗效的相关预后因素。方法我院2001年1月至2008年5月荧光原位杂交检查确诊为原发BCR/ABL+-ALL59例,经VDLP±Ara-C方案诱导化疗,化疗不缓解者或准备移植者给予伊马替尼治疗,其中接受伊马替尼联合治疗17例,行异基因造血干细胞移植(allo-HSCT)16例。结果59例BCR/ABL+-ALL患者中位年龄32(3～69)岁,经第1疗程诱导治疗后获CR共32例(54.2%)。外周血白细胞计数<30×109/L、30～99.9×109/L和≥100×109/L的CR率分别是75.0%(18/24例)、56.3%(9/15例)和26.3%(5/19例)(P=0.006),2年总生存率(OS)分别是24.7%、22.5%和21.1%(P=0.180)。FAB分型:L1、L2、急性混合性白血病的CR率分别是66.7%(6/9例)、63.2%(24/38例)和22.2%(2/9例)(P=0.029),2年OS分别是22.2%、27.0%和22.0%(P=0.623)。免疫分型:单纯ALL、伴髓系抗原表达ALL、急性混合性白血病的CR率分别是61.1%(11/18例)、60.6%(20/33例)和12.5%(1/8例)(P=0.039),2年OS分别是22.7%、21.0%和18.8%(P=0.643)。染色体核型:正常核型、单纯t(9;22)、Ph+伴附加染色体异常的CR率分别是71.4%(5/7例)、70.8%(17/24例)和37.5%(9/24例)(P=0.046),2年OS分别是42.9%、34.0%和7.3%(P=0.000)。是否合并败血症的2年OS分别是5.0%和36.0%(P=0.005)。含伊马替尼治疗组与不含伊马替尼治疗组、接受allo-HSCT治疗组和仅化疗组的2年OS分别是48.0%和11.2%(P=0.001)、54.2%和8.5%(P=0.000)。结论外周血白细胞计数≥100×109/L、形态学或免疫学类型为急性混合性白血病、Ph+伴附加染色体异常对BCR/ABL+-ALL的疗效有一定的负性影响,Ph+伴附加染色体异常、合并败血症者生存期短,伊马替尼联合治疗和allo-HSCT均可延长BCR/ABL+-ALL的生存期。

Objective To study the clinical characteristics and outcomes of BCR/ABL-positive acute lymphoblastic leukemia （BCR/ABL^＋-ALL） and screen the prognostic factors for BCR/ABL^＋-ALL. Methods From January 2001 to May 2008, 59 patients （median age of 32 years ranging from 3 to 69 years） with the diagnosis of BCR/ABL^＋-ALL by fluorescence in situ hybridization received induction chemotherapy with VDLP ±Ara-C regimen. The patients who failed to respond to the chemotherapy received subsequent consolidation chemotherapy with imatinib （400-800 mg/day） （17 cases） or allogeneic hematopoietic stem cell transplantation （allo-HSCT） （16 cases）. Results Of the 59 patients, 32 （58.3%） achieved complete remission （CR） after the first induction cycle. In patients with peripheral white blood cell （WBC） count 〈30× 10^9/L, 30-99.9× 10^9/L and ≥ 100×10^9/L, the CR rates were 75.0% （18/24）, 56.3% （9/15） and 26.3% （5/19） （P=0.006）, and the overall survival probability of 2 years （ OSs of 2-yrs） was 24.7%, 22.5% and 21.1%, respectively （P=0.180）. According to the FAB classification, 56 cases were divided into L1, L2 and biphenotypic acute leukemia （BAL） subgroups, and their CR rates were 66.7% （6/9）, 63.2% （24/38） and 22.2% （2/9） （P=0.029）, with OSs of 2-yrs of 22.2%, 27.0% and 22.0%, respectively （P=0.623）. In terms of immunophenotype grouping by EGIL, the patients with ALL, myeloid antigen-positive ALL and BAL had CR rates of 61.1% （11/18）, 60.6% （20/33） and 12.5% （1/8） （P=0.039）, and the OSs of 2-yrs of 22.7%, 21.0% and 18.8%, respectively （P=0.643）. In 55 patients with known karyotype, the CR rates were 71.4%（5/7）, 70.8% （17/24） and 37.5% （9/24） innormal, sole t（9;22） abnormality, t （9;22） with additional abnormalities groups （P=0.046）, with the OSs of 2-yrs of 42.9%, 34.0% and 7.3%, respectively （P=0.000）. The patients complicated by septicemia had significantly lower OSs of 2-yrs than those without septicemia （0% vs 38.8%, P=0.005）. The OSs of 2-yrs were significantly higher in patients with consolidation chemotherapy with imatinib than those without （48.0% vs 11.2%, P=-0.001）, and allo-HSCT was associated with significantly higher OSs of 2-yrs than exclusive chemotherapy （54.2% and 8.5%, P=-0.000）. Conclusion BCR/ABL^＋-ALL with WBC ≥ 100×10^9/L, presence of BAL diagnosed by FAB or FACM, t（9;22） with additional chromosome abnormalites all adversely affect the treatment results,and additional chromosome abnormalites and septicemia are associated with lower OSs of 2-yrs. Imatinib treatment and allo-HSCT can both improve the OSs of 2-yrs of the patients with BCR/ABL^＋-ALL.