Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China

CAI Chun-Xia; ZHENG Yong-Zhi; LI Jian; WEN Hong; WENG Kai-Zhi; ZHUANG Shu-Quan; WU Xing-Guo; LE Shao-Hua

doi:10.7499/j.issn.1008-8830.2208126

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Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (1) : 38-45. DOI: 10.7499/j.issn.1008-8830.2208126

Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China

CAI Chun-Xia, ZHENG Yong-Zhi, LI Jian, WEN Hong, WENG Kai-Zhi, ZHUANG Shu-Quan, WU Xing-Guo, LE Shao-Hua

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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.

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Acute lymphoblastic leukemia / High hyperdiploid / Prognosis / Child

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CAI Chun-Xia, ZHENG Yong-Zhi, LI Jian, WEN Hong, WENG Kai-Zhi, ZHUANG Shu-Quan, WU Xing-Guo, LE Shao-Hua. Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(1): 38-45 https://doi.org/10.7499/j.issn.1008-8830.2208126

References

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.