Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia:: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis
Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia:: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis
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DOI：
10.1182/blood.v99.5.1536
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发表时间：
2002-03-01
期刊：
影响因子：
20.3
通讯作者：
Thiel, E
中科院分区：
文献类型：
--
作者：
Gleissner, B;Gökbuget, N;Thiel, E
BCR-ABL融合，费城易位的分子等价物，在成人急性淋巴细胞白血病（ALL）的治疗分层中获得重要性。在这项前瞻性研究中，对478例CD 10（+）前体B细胞ALL（c-ALL和pre-B ALL）患者的样本进行了BCR-ABL逆转录聚合酶链反应（RT-PCR）分析，并对阳性样本进行了双重检测。根据PCR结果对患者进行分层，并在2项德国成人ALL多中心试验中接受治疗。随访结果，并将BCR-ABL的预后影响与临床风险特征进行比较。在478个样本中，432个具有可评价的BCR-ABL结果。37%的c-ALL和pre-B ALL患者为BCR-ABL（+）（p190，77%; p210，20%;同时p190/p210，3%）。BCR-ABL阳性与年龄较大（中位年龄45岁对30岁; P = 0.0001）和白色细胞计数较高（23500/μ L对11550/穆尔; P = 0.0001）的高危特征相关。单变量和多变量分析显示，与临床风险标准相比，BCR-ABL是预后不良的主要因素（P =.0001）。无论断点如何，任何BCR-ABL转录本的存在都预测初始治疗应答的机会较低（68.4%对84.6%; P = 0.001），3年无病生存率的概率较低（0.13对0.47; P = 0.0001）。这种不良结局不受诱导后高剂量治疗分层的影响。结果显示BCR-ABL融合转录物的高流行率，以p190为主。BCR-ABL RT-PCR被证实是诊断t（9;22）的一种敏感、快速的方法，p190和p210被明确证明是尽管加强化疗但长期生存率差的最重要预测因子。(C)2002年，美国血液学会。
The BCR-ABL fusion, the molecular equivalent of the Philadelphia translocation, gains Importance for treatment stratification in adult acute lymphoblastic leukemia (ALL). In this prospective study, samples from 478 patients with CD10(+) B-cell precursor ALL (c-ALL and pre-B ALL) underwent BCR-ABL reverse transcription-polymerase chain reaction (RT-PCR) analysis with double testing of positive samples. Patients were stratified according to the PCR result and treated in 2 German Multicenter Trials of Adult ALL. The outcome was followed and the prognostic impact of BCR-ABL was compared to clinical risk features. of the 478 samples, 432 had an evaluable BCR-ABL result. Thirty-seven percent of the c-ALL and pre-B ALL patients were BCR-ABL(+) (p190, 77%; p210, 20%; simultaneous p190/p210, 3%). BCR-ABL positivity was associated with the high-risk features of older age (45 years versus 30 years median age; P =.0001) and higher white blood cell counts (23 500/muL versus 11 550/muL; P =.0001). Univariate and multivariate analyses revealed BCR-ABL as the leading factor for a poor prognosis (P =.0001) in comparison to clinical risk criteria. Irrespective of the breakpoint, presence of any BCR-ABL transcript predicted a lower chance of initial treatment response (68.4% versus 84.6%; P =.001) and a lower probability of disease-free survival at 3 years (0.13 versus 0.47; P =.0001). This bad outcome was not influenced by postinduction high-dose treatment stratifications. The results show a high prevalence of BCR-ABL fusion transcripts with predominance of p190. BCR-ABL RT-PCR is confirmed as a sensitive, rapid method to diagnose t(9;22), and p190 and p210 are unequivocally demonstrated as the most important predictors of poor long-term survival despite intensified chemotherapy. (C) 2002 by The American Society of Hematology.