Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study
Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study
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DOI：
10.1038/leu.2008.312
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发表时间：
2009-02-01
期刊：
影响因子：
11.4
通讯作者：
Patte, C.
中科院分区：
文献类型：
--
作者：
Poirel, H. A.;Cairo, M. S.;Patte, C.
临床研究表明，晚期、高LDH、对还原治疗反应差以及合并骨髓和中枢神经系统疾病与接受FAB/LMB 96治疗的儿童成熟B细胞非霍奇金淋巴瘤（B-NHL）的无事件生存期（EFS）降低显著相关。虽然重排MYC/8 q24（R8 q24）是伯基特淋巴瘤（BL）的特征，但关于其他细胞遗传学异常及其预后重要性的信息很少。我们对接受FAB/LMB 96治疗的238例儿童成熟B-NHL的异常核型进行了国际审查：76% BL，8% Burkitt样淋巴瘤，13%弥漫性大B细胞淋巴瘤（DLBCL）。主要的BL R8 q24相关染色体畸变为+1q（29%）、+7q和del（13 q）（各14%）。DLBCL表现为异质性和更复杂。R8 q24的发生率（34%）高于成人DLBCL的报告。通过控制已知风险因素的考克斯模型研究细胞遗传学异常对EFS的预后价值：R8 q24、+7 q和del（13 q）与显著劣化EFS独立相关（风险比分别为：6.1（P = 0.030）、2.5（P = 0.015）和4.0（P = 0.0003））。仅在DLBCL中观察到R8 q24的不良预后，而del（13 q）和+7q在DLBCL和BL中具有相似的影响。这些结果强调了儿童期成熟B-NHL的显著生物异质性和细胞遗传学风险适应性治疗的发展。
Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event-free survival (EFS) in pediatric mature B-cell non-Hodgkin's lymphoma (B-NHL) treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24-associated chromosomal aberrations were +1q (29%), +7q and del(13q) (14% each). The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 (34%) was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS (hazard ratio: 6.1 (P = 0.030), 2.5 (P = 0.015) and 4.0 (P = 0.0003), respectively). The adverse prognosis of R8q24 was observed only in DLBCL, whereas del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk-adapted therapy in childhood mature B-NHL.