目的 探讨儿童高超二倍体（high hyperdiploid，HHD）急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）的临床特征及预后。 方法 回顾性分析2011年4月—2020年12月福建省5家医院收治的1 414例ALL初诊患儿的临床资料。根据染色体核型，分为伴HHD组（172例）和不伴HHD组（1 242例），比较两组的临床特征及疗效，并进一步探讨HHD ALL的预后影响因素。 结果 在1 414例ALL初诊患儿中，172例（12.16%）检出HHD。伴HHD组初诊有不良预后危险因素（起病年龄≥10岁或<1岁、初诊白细胞计数≥50×109/L、T细胞表型）、常见融合基因（TEL-AML1、BCR-ABL1、E2A-PBX1、MLL基因重排）阳性的患儿比例均低于不伴HHD组（均P<0.05），而诱导化疗后微小残留病（minimal residual disease，MRD）<0.01%的患儿比例高于不伴HHD组（P<0.05）。伴HHD组预期10年无事件生存（event-free survival，EFS）率及总生存率均高于不伴HHD组（P<0.05）。单因素分析显示，染色体数目58~66、10号染色体三体、17号染色体三体、诱导化疗第15天或第19天骨髓MRD<1%、诱导化疗第33天或第46天骨髓MRD<0.01%是高EFS率的影响因素（均P<0.05）；10号染色体三体与高总生存率有关（P<0.05）。Cox比例风险回归模型分析显示，17号染色体三体与高EFS率密切相关（P<0.05）。 结论 儿童HHD ALL初诊时不良预后危险因素较少，总体预后佳；染色体数目及特定染色体三体与预后相关。
Abstract
Objective To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL). Methods A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored. Results Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×109/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05). Conclusions The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.
关键词
急性淋巴细胞白血病 /
超二倍体 /
预后 /
儿童
Key words
Acute lymphoblastic leukemia /
High hyperdiploid /
Prognosis /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
1 Pui CH. Precision medicine in acute lymphoblastic leukemia[J]. Front Med, 2020, 14(6): 689-700. PMID: 33074527. DOI: 10.1007/s11684-020-0759-8.
2 中华医学会儿科学分会血液学组, 《中华儿科杂志》编辑委员会. 儿童急性淋巴细胞白血病诊疗建议(第四次修订)[J]. 中华儿科杂志, 2014, 52(9): 641-644. DOI: 10.3760/cma.j.issn.0578-1310.2014.09.001.
3 Dastugue N, Suciu S, Plat G, et al. Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results[J]. Blood, 2013, 121(13): 2415-2423. PMID: 23321258. DOI: 10.1182/blood-2012-06-437681.
4 Kato M, Imamura T, Manabe A, et al. Prognostic impact of gained chromosomes in high-hyperdiploid childhood acute lymphoblastic leukaemia: a collaborative retrospective study of the Tokyo Children's Cancer Study Group and Japan Association of Childhood Leukaemia Study[J]. Br J Haematol, 2014, 166(2): 295-298. PMID: 24628674. DOI: 10.1111/bjh.12836.
5 Cui L, Li ZG, Chai YH, et al. Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: the first nation-wide prospective multicenter study in China[J]. Am J Hematol, 2018, 93(7): 913-920. PMID: 29675840. DOI: 10.1002/ajh.25124.
6 刘旭平, 竺晓凡, 王建祥, 等. 成人与儿童急性淋巴细胞白血病细胞遗传学大样本对比分析[J]. 中国实验血液学杂志, 2009, 17(6): 1399-1404. PMID: 20030914.
7 Brothman AR, Persons DL, Shaffer LG. Nomenclature evolution: changes in the ISCN from the 2005 to the 2009 edition[J]. Cytogenet Genome Res, 2009, 127(1): 1-4. PMID: 20110655. DOI: 10.1159/000279442.
8 许凤玲, 管贤敏, 温贤浩, 等. 儿童急性淋巴细胞白血病化疗相关严重不良反应的临床分析[J]. 中国当代儿科杂志, 2020, 22(8): 828-833. PMID: 32800028. PMCID: PMC7441514. DOI: 10.7499/j.issn.1008-8830.2003253.
9 潘丽丽, 郑湧智, 乐少华, 等. CCCG-ALL 2015方案与CCLG-ALL 2008方案治疗儿童急性淋巴细胞白血病的早期疗效及严重不良事件对比[J]. 中国实验血液学杂志, 2022, 30(3): 726-731. PMID: 35680796. DOI: 10.19746/j.cnki.issn1009-2137.2022.03.010.
10 Paulsson K, Forestier E, Andersen MK, et al. High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols[J]. Haematologica, 2013, 98(9): 1424-1432. PMID: 23645689. PMCID: PMC3762100. DOI: 10.3324/haematol.2013.085852.
11 Paulsson K. High hyperdiploid childhood acute lymphoblastic leukemia: chromosomal gains as the main driver event[J]. Mol Cell Oncol, 2016, 3(1): e1064555. PMID: 27308574. PMCID: PMC4845247. DOI: 10.1080/23723556.2015.1064555.
12 Moorman AV, Richards SM, Martineau M, et al. Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia[J]. Blood, 2003, 102(8): 2756-2762. PMID: 12829593. DOI: 10.1182/blood-2003-04-1128.
13 Szczepański T, Harrison CJ, van Dongen JJ. Genetic aberrations in paediatric acute leukaemias and implications for management of patients[J]. Lancet Oncol, 2010, 11(9): 880-889. PMID: 20435517. DOI: 10.1016/S1470-2045(09)70369-9.
14 Heerema NA, Sather HN, Sensel MG, et al. Prognostic impact of trisomies of chromosomes 10, 17, and 5 among children with acute lymphoblastic leukemia and high hyperdiploidy (>50 chromosomes)[J]. J Clin Oncol, 2000, 18(9): 1876-1887. PMID: 10784628. DOI: 10.1200/JCO.2000.18.9.1876.
15 Moorman AV, Ensor HM, Richards SM, et al. Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial[J]. Lancet Oncol, 2010, 11(5): 429-438. PMID: 20409752. DOI: 10.1016/S1470-2045(10)70066-8.
16 Li X, Li J, Hu Y, et al. A comprehensive cytogenetic classification of 1466 Chinese patients with de novo acute lymphoblastic leukemia[J]. Leuk Res, 2012, 36(6): 720-726. PMID: 22264634. DOI: 10.1016/j.leukres.2011.12.016.
17 Chen B, Wang YY, Shen Y, et al. Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic patterns in 1 346 childhood and adult cases and their comparison with the reports from western countries[J]. Leukemia, 2012, 26(7): 1608-1616. PMID: 22382891. DOI: 10.1038/leu.2012.26.
18 Liang DC, Shih LY, Yang CP, et al. Frequencies of ETV6-RUNX1 fusion and hyperdiploidy in pediatric acute lymphoblastic leukemia are lower in far east than west[J]. Pediatr Blood Cancer, 2010, 55(3): 430-433. PMID: 20658612. DOI: 10.1002/pbc.22628.
19 Sutcliffe MJ, Shuster JJ, Sather HN, et al. High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI standard-risk B-precursor acute lymphoblastic leukemia: a Children's Oncology Group (COG) initiative[J]. Leukemia, 2005, 19(5): 734-740. PMID: 15789069. DOI: 10.1038/sj.leu.2403673.
20 Enshaei A, Vora A, Harrison CJ, et al. Defining low-risk high hyperdiploidy in patients with paediatric acute lymphoblastic leukaemia: a retrospective analysis of data from the UKALL97/99 and UKALL2003 clinical trials[J]. Lancet Haematol, 2021, 8(11): e828-e839. PMID: 34715050. PMCID: PMC8567211. DOI: 10.1016/S2352-3026(21)00304-5.
21 Inaba H, Pei D, Wolf J, et al. Infection-related complications during treatment for childhood acute lymphoblastic leukemia[J]. Ann Oncol, 2017, 28(2): 386-392. PMID: 28426102. PMCID: PMC5834143. DOI: 10.1093/annonc/mdw557.
22 Vora A, Goulden N, Wade R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial[J]. Lancet Oncol, 2013, 14(3): 199-209. PMID: 23395119. DOI: 10.1016/S1470-2045(12)70600-9.
PDF(734 KB)
