478例急性髓系白血病患儿的染色体异常：一项儿童肿瘤协作组研究（POG 8821）中的临床特征及治疗结果

Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821.

作者信息

Raimondi S C, Chang M N, Ravindranath Y, Behm F G, Gresik M V, Steuber C P, Weinstein H J, Carroll A J

机构信息

Departments of Pathology and Laboratory Medicine, St Jude Children's Research Hospital, and University of Tennessee, Memphis, TN 38105, USA.

出版信息

Blood. 1999 Dec 1;94(11):3707-16.

PMID:10572083

Abstract

We determined the type and frequency of chromosomal aberrations in leukemic cells of 478 children diagnosed with acute myeloid leukemia and enrolled in the Pediatric Oncology Group study 8821. Of the 478 cases, 109 (22.8%) had normal karyotypes. Chromosomal abnormalities of 280 patients (58.6%) were classified into subgroups: 11q23 abnormalities (n = 88, 18.4%), t(8;21) (n = 56, 11.7%), t(15;17) (n = 55, 11.5%), inv(16)/t(16;16) (n = 28, 5.9%), trisomy 8 alone (n = 10, 2.1%), monosomy 7 (n = 9, 1.9%), non-Down-associated trisomy 21 alone (n = 7, 1.5%), and rare recurrent chromosomal translocations (n = 27, 5.6%). The remaining 89 patients (18.6%) had miscellaneous clonal abnormalities. Overall, 84.9% of the children achieved a complete remission; the 4-year event-free survival (EFS) estimate was 33.8% +/- 2.4%. Remission rates were significantly higher (96.4%, P =.011) for patients with t(8;21) and inv(16)/t(16;16) but significantly lower (74.5%, P =.022) for those with t(15;17). The 4-year survival rate for all patients was 43.5% +/- 2.4%; for those with an inv(16)/t(16;16), 75.0% +/- 8.6%; a normal karyotype, 53.8% +/- 4.9%; a t(8;21), 51.6% +/- 7.3%; a t(15;17), 39.8% +/- 6.9%; and an 11q23 abnormality, 32.9% +/- 5.1%. Four-year EFS estimates for patients with inv(16)/t(16;16) (58.2% +/- 10.9%, P =.007), t(8;21) (45.1% +/- 7.7%, P =.014), or normal karyotypes (43.1% +/- 5.0%, P =. 012) were higher than the 4-year EFS estimate for all patients, but EFS estimates for patients with t(15;17) (19.6% +/- 8.0%, P =.033) or 11q23 abnormalities (23.8% +/- 4.8%, P =.0013) were lower. EFS estimates did not differ significantly among 11q23 subgroups. Limited analysis suggested that patients with inv(16) can be salvaged better following relapse than those with t(8;21). Thus, patients with an inv(16)/t(16;16) may have high survival rates when treated with chemotherapy alone.

摘要

我们确定了478名被诊断为急性髓细胞白血病并参与儿童肿瘤学组8821研究的儿童白血病细胞中的染色体畸变类型和频率。在这478例病例中，109例（22.8%）核型正常。280例患者（58.6%）的染色体异常被分为亚组：11q23异常（n = 88，18.4%）、t(8;21)（n = 56，11.7%）、t(15;17)（n = 55，11.5%）、inv(16)/t(16;16)（n = 28，5.9%）、单纯8号染色体三体（n = 10，2.1%）、7号染色体单体（n = 9，1.9%）、非唐氏综合征相关的单纯21号染色体三体（n = 7，1.5%）以及罕见的复发性染色体易位（n = 27，5.6%）。其余89例患者（18.6%）有其他克隆异常。总体而言，84.9%的儿童实现了完全缓解；4年无事件生存率（EFS）估计为33.8%±2.4%。t(8;21)和inv(16)/t(16;16)患者的缓解率显著更高（96.4%，P = 0.011），而t(15;17)患者的缓解率显著更低（74.5%，P = 0.022）。所有患者的4年生存率为43.5%±2.4%；inv(16)/t(16;16)患者为75.0%±8.6%；核型正常者为53.8%±4.9%；t(8;21)患者为51.6%±7.3%；t(15;17)患者为39.8%±6.9%；11q23异常患者为32.9%±5.1%。inv(16)/t(16;16)（58.2%±10.9%，P = 0.007）、t(8;21)（45.1%±7.7%，P = 0.014）或核型正常患者（43.1%±5.0%，P = 0.012）的4年EFS估计高于所有患者的4年EFS估计，但t(15;17)患者（19.6%±8.0%，P = 0.033）或11q23异常患者（23.8%±4.8%，P = 0.0013）的EFS估计更低。11q23亚组之间的EFS估计无显著差异。有限的分析表明，inv(16)患者复发后比t(8;21)患者更容易挽救。因此，单纯化疗治疗inv(16)/t(16;16)患者可能有较高的生存率。