Clinical and Cytogenetic Features of a Population-Based Consecutive Series of 285 Pediatric T-Cell Acute Lymphoblastic Leukemias: Rare T-cell Receptor Gene Rearrangements Are Associated with Poor Outcome
Clinical and Cytogenetic Features of a Population-Based Consecutive Series of 285 Pediatric T-Cell Acute Lymphoblastic Leukemias: Rare T-cell Receptor Gene Rearrangements Are Associated with Poor Outcome
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DOI：
10.1002/gcc.20684
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发表时间：
2009-09-01
影响因子：
3.7
通讯作者：
Johansson, Bertil
中科院分区：
文献类型：
--
作者：
Karrman, Kristina;Forestier, Erik;Johansson, Bertil
在1992年至2006年在北欧国家诊断的285例儿童T细胞急性淋巴细胞白血病（T-ALL）的人群连续系列中，确定并审查了临床特征和细胞遗传学畸变。在249例（87%）病例中获得了信息性核型结果，其中119例（48%）为细胞遗传学异常。大多数（62%）的异常T-ALL是假二倍体。结构变化比数值变化更常见; 86%显示至少有一个结构异常，41%至少有一个数值异常。最常见的异常是T细胞受体（TCR）基因重排（20%）[TCR; 11 p13（10%），TCR; 10 q24（3%），TCR;其他（8%）]，del（9 p）（17%），+8（14%），del（6 q）（12%）和11 q23重排（6%）。T细胞受体（TCR）组：t（X; 14）（p11;q11），t（X;7）（q22;q34），t（1;14）（p32;q11），ins（14;5）（q11;q？q？），inv（7）（p15q34）、t（8;14）（q24;q11）、t（7;11）（q34;p15）和t（12; 14）（p13;q11）。该北欧患者队列的临床特征与之前的大型系列研究一致，中位年龄为9.0岁，男性占优势（男/女比3.1），中位白色血细胞（WBC）计数为66.5 x 10（9）/1，纵隔肿块和中枢神经系统受累的发生率较高（分别为59%和9.5%）。这些特征在不同的遗传亚群中没有显著差异。5-所有患者的年无事件生存率（EFS）和总生存率分别为0.61（+/-0.03）和0.67（+/-0.03）。在多变量分析中，有两个因素对EFS产生负面影响，即WBC计数>= 200 × 10（9）/1（P < 0.001）和罕见TCR重排的存在（P = 0.001）。总之，在来自北欧国家的这一大型儿童T-ALL系列中，细胞遗传学结果与治疗失败风险无关，TCR除外;其他组。然而，需要进一步的前瞻性和合作调查，这种遗传异质性的实体，以确认这些结果。(C)2009 Wiley-Liss，Inc.
Clinical characteristics and cytogenetic aberrations were ascertained and reviewed in a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias (T-ALLs) diagnosed between 1992 and 2006 in the Nordic countries. Informative karyotypic results were obtained in 249 (87%) cases, of which 119 (48%) were cytogenetically abnormal. Most (62%) of the aberrant T-ALLs were pseudodiploid. Structural changes were more common than numerical ones; 86% displayed at least one structural abnormality and 41% at least one numerical anomaly. The most frequent abnormalities were T-cell receptor (TCR) gene rearrangements (20%) [TCR; 11p13 (10%), TCR; 10q24 (3%), TCR;other (8%)], del(9p) (17%), +8 (14%), del(6q) (12%), and 11q23 rearrangements (6%). The TCR;other group comprised the rare rearrangements t(X; 14)(p11;q11), t(X;7)(q22;q34), t(1;14)(p32;q11), ins(14;5)(q11;q?q?), inv(7)(p15q34), t(8;14)(q24;q11), t(7;11)(q34;p15), and t(12;1 4)(p13;q11). The clinical characteristics of this Nordic patient cohort agreed well with previous larger series, with a median age of 9.0 years, male predominance (male/female ratio 3.1), median white blood cell (WBC) count of 66.5 x 10(9)/1, and a high incidence of mediastinal mass and central nervous system involvement (59% and 9.5%, respectively). These features did not differ significantly among the various genetic subgroups. 5-year event-free survival (EFS) and overall survival for all patients were 0.61 (+/-0.03) and 0.67 (+/-0.03), respectively. In a multivariate analysis, two factors affected negatively the EFS, namely a WBC count of >= 200 x 10(9)/1 (P < 0.001) and the presence of rare TCR rearrangements (P = 0.001). In conclusion, in this large series of childhood T-ALLs from the Nordic countries, the cytogenetic findings were not associated with risk of therapy failure with the exception of the TCR;other group. However, further prospective and collaborative investigations of this genetically heterogeneous entity are needed to confirm these results. (C) 2009 Wiley-Liss, Inc.