Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria

GAO Hui-Qin; GUAN Xian-Min; WEN Xian-Hao; SHEN Ya-Li; GUO Yu-Xia; DOU Ying; MENG Yan; YU Jie

doi:10.7499/j.issn.1008-8830.2105004

PDF(596 KB)

Chinese Journal of Contemporary Pediatrics ›› 2021, Vol. 23 ›› Issue (8) : 835-840. DOI: 10.7499/j.issn.1008-8830.2105004

CLINICAL RESEARCH

Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria

GAO Hui-Qin, GUAN Xian-Min, WEN Xian-Hao, SHEN Ya-Li, GUO Yu-Xia, DOU Ying, MENG Yan, YU Jie

Author information +

History +

Abstract

Objective To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. Methods A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. Results The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (P<0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P<0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1, positive MLL-r, and hyperleukocytosis (white blood cell count ≥50×10⁹/L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P>0.05). Conclusions ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

Key words

Acute leukemias of ambiguous lineage / Diagnostic criteria / Prognosis / Child

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

GAO Hui-Qin, GUAN Xian-Min, WEN Xian-Hao, SHEN Ya-Li, GUO Yu-Xia, DOU Ying, MENG Yan, YU Jie. Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria[J]. Chinese Journal of Contemporary Pediatrics. 2021, 23(8): 835-840 https://doi.org/10.7499/j.issn.1008-8830.2105004

References

1 Jaffe ES, Harris NL, Stein H, et al. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues[M]. Lyon: IARC Press, 2001: 106-107.
2 Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL)[J]. Leukemia, 1995, 9(10):1783-1786. PMID:7564526.
3 Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 127(20): 2391-2405. DOI: 10.1182/blood-2016-03-643544. PMID: 27069254.
4 Maruffi M, Sposto R, Oberley MJ, et al. Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis[J]. Leukemia, 2018, 32(7): 1515-1528. DOI: 10.1038/s41375-018-0058-4. PMID: 29550836.PMCID: PMC7508489.
5 Weinberg OK, Seetharam M, Ren L, et al. Mixed phenotype acute leukemia: a study of 61 cases using World Health Organization and European Group for the Immunological Classification of Leukaemias criteria[J]. Am J Clin Pathol, 2014, 142(6): 803-808. DOI: 10.1309/AJCPPVUPOTUVOIB5. PMID: 25389334.
6 Pomerantz A, Rodriguez-Rodriguez S, Demichelis-Gomez R, et al. Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used[J]. Blood Res, 2016, 51(4): 233-241. DOI: 10.5045/br.2016.51.4.233. PMID: 28090485. PMCID: PMC5234234.
7 Hrusak O, de Haas V, Stancikova J, et al. International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia[J]. Blood, 2018, 132(3): 264-276. DOI: 10.1182/blood-2017-12-821363. PMID: 29720486.
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. DOI: 10.7499/j.issn.1008-8830.2003253. PMID: 32800028. PMCID: PMC7441514.
9 杨脉. 2015-AML03方案治疗儿童急性髓细胞白血病91例结果分析[D]. 重庆: 重庆医科大学, 2019.
10 秘营昌, 卞寿庚. 急性白血病[M]. 3版. 北京: 科学出版社, 2007: 131-133.
11 Orgel E, Alexander TB, Wood B, et al. Efficacy of all therapy for WHO2016-defined mixed phenotype acute leukemia: a report from the Children's Oncology Group[J]. Blood, 2017, 130(Suppl_1): 883. DOI: 10.1182/blood.V130.Suppl_1.883.883.
12 Al-Seraihy AS, Owaidah TM, Ayas M, et al. Clinical characteristics and outcome of children with biphenotypic acute leukemia[J]. Haematologica, 2009, 94(12): 1682-1690. DOI: 10.3324/haematol.2009.009282. PMID: 19713227. PMCID: PMC2791935.
13 Rubnitz JE, Onciu M, Pounds S, et al. Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital[J]. Blood, 2009, 113(21): 5083-5089. DOI: 10.1182/blood-2008-10-187351. PMID: 19131545. PMCID: PMC2686179.
14 Oberley MJ, Raikar SS, Wertheim GB, et al. Significance of minimal residual disease in pediatric mixed phenotype acute leukemia: a multicenter cohort study[J]. Leukemia, 2020, 34(7): 1741-1750. DOI: 10.1038/s41375-020-0741-0. PMID: 32060402. PMCID: PMC7332384.
15 Orgel E, Oberley M, Li SS, et al. Predictive value of minimal residual disease in WHO2016-defined mixed phenotype acute leukemia (MPAL)[J]. Blood, 2016, 128(22): 178. DOI: 10.1182/blood.V128.22.178.178.
16 Gerr H, Zimmermann M, Schrappe M, et al. Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations[J]. Br J Haematol, 2010, 149(1): 84-92. DOI: 10.1111/j.1365-2141.2009.08058.x. PMID: 20085575.
17 Gao H, Liu Y, Zhang R, et al. Pediatric mixed phenotype acute leukemia—41 cases report[J]. Blood, 2012, 120(21): 4811. DOI: 10.11406/rinketsu.59.75.
18 Qasrawi A, Ramlal R, Munker R, et al. Prognostic impact of Philadelphia chromosome in mixed phenotype acute leukemia (MPAL): a cancer registry analysis on real-world outcome[J]. Am J Hematol, 2020, 95(9): 1015-1021. DOI: 10.1002/ajh.25873. PMID: 32419244.
19 McGinnis E, Yang D, Au N, et al. Clinical and laboratory features associated with myeloperoxidase expression in pediatric B-lymphoblastic leukemia[J]. Cytometry B Clin Cytom, 2020. DOI: 10.1002/cyto.b.21966. PMID: 33048471. Epub ahead of print.
20 Raikar SS, Park SI, Leong T, et al. Isolated myeloperoxidase expression in pediatric B/myeloid mixed phenotype acute leukemia is linked with better survival[J]. Blood, 2018, 131(5): 573-577. DOI: 10.1182/blood-2017-09-807602. PMID: 29223952.
21 Oberley MJ, Li S, Orgel E, et al. Clinical significance of isolated myeloperoxidase expression in pediatric B-Lymphoblastic leukemia[J]. Am J Clin Pathol, 2017, 147(4): 374-381. DOI: 10.1093/ajcp/aqx021. PMID: 28340210.