Seeger K, von Stackelberg A, Taube T, Buchwald D, Körner G, Suttorp M, Dörffel W, Tausch W, Henze G
Department of Pediatric Oncology/Hematology, Charité Medical Center, Humboldt-University, Berlin, Germany.
J Clin Oncol. 2001 Jul 1;19(13):3188-93. doi: 10.1200/JCO.2001.19.13.3188.
The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor.
A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL-negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse.
Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 +/- 0.10 versus 0.38 +/- 0.10 (P =.09) and 0.82 +/- 0.09 versus 0.42 +/- 0.19 (P =.10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P <.001) but not of TEL-AML1 expression (P =.09).
TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.
本研究旨在调查在复发性儿童急性淋巴细胞白血病(ALL)中,由隐匿性染色体易位t(12;21)(p13;q22)导致的TEL-AML1融合这一常见基因特征是否为独立危险因素。
在柏林-法兰克福-明斯特研究组的ALL-复发试验ALL-Rezidiv(REZ)治疗的BCR-ABL阴性B细胞前体(BPC)ALL首次复发的同质儿童组中进行配对分析。共有249例患者符合本研究条件:53例(21%)TEL-AML1阳性,196例(79%)阴性。阳性患者在复发时的既定最显著预后决定因素、复发时间点和部位以及复发时的年龄和外周原始细胞计数方面进行配对。
可以确定50对符合上述标准的配对。配对的TEL-AML1阳性和阴性患者的无事件生存率和5年生存率(含SE)分别为0.63±0.10对0.38±0.10(P = 0.09)和0.82±0.09对0.42±0.19(P = 0.10)。多变量分析证实了这些结果,显示复发时间点和部位具有独立的预后意义(均P < 0.001),但TEL-AML1表达无此意义(P = 0.09)。
在对相关预后参数进行配对后,TEL-AML1表达在复发性儿童BCP-ALL中不构成独立危险因素。它无疑在基因上表征了一个与既定良好预后参数相关的ALL实体。应谨慎考虑诸如异基因造血干细胞移植等高风险治疗程序。