Infant acute leukemia in children: Clinical and cytogenetic characteristics (A retrospective study)

Zh.O. Ospanova; A.T. Saduova; G.K. Kemer; G.A. Nurzhanova

doi:10.37800/RM.2.2026.675

Authors

Zh.O. Ospanova
A.T. Saduova
G.K. Kemer НАО «Казахский Национальный медицинский университет имени С.Д. Асфендиярова»
G.A. Nurzhanova

DOI:

https://doi.org/10.37800/RM.2.2026.675

Keywords:

leukemia, KMT2A protein, immunophenotyping, cytogenetics, children under one year of age

Abstract

Relevance: Infant leukemia is defined as a condition in which leukemic cells are detected at birth or within the first months of life. Although from cytological and histological perspectives, acute leukemia in infants resembles forms observed in older children and adults, it is distinguished by specific clinical and genetic features. The clinical course of infant leukemia is typically marked by rapid onset, a high leukocyte burden, frequent extramedullary manifestations -including involvement of the central nervous system, liver, and spleen – and a high risk of early complications.

The study aimed to assess the clinical features and early diagnostic characteristics of infant leukemia in children under one year of age in the Republic of Kazakhstan.

Materials and Methods: This retrospective study included 16 infants (<1 year of age) diagnosed with acute leukemia and treated at the Scientific Center of Pediatrics and Pediatric Surgery, Almaty, Republic of Kazakhstan, between 2018 and 2023.

Results: Genetic and congenital disorders were identified in children with infant leukemia. Down syndrome was diagnosed in 18.8% of patients (3/16), and trisomy 8 and intrauterine infection were each identified in one patient. Morphological analysis revealed a predominance of acute lymphoblastic leukemia (75%), while acute myeloblastic leukemia accounted for 25% of cases. In our study, rearrangements in the Mixed Lineage Leukemia (KMT2A, 11q23) gene were detected in approximately 91% of cases. The most frequent translocation was t(4;11)(q21;q23), observed in 30% of patients.

Conclusion: The identified cytogenetic and immunological features, including the high prevalence of the t(4;11) translocation, are associated with an unfavorable prognosis, primary resistance to therapy, and a high risk of early relapse. These findings underscore the need for early molecular genetic and immunophenotypic profiling, as well as the development and implementation of risk-adapted therapeutic strategies for infants with acute leukemia.

References

1. Tsujimoto H, Kounami S, Mitani Y, Watanabe T, Takifuji K. Neonatal acute megakaryoblastic leukemia presenting with leukemia cutis and multiple intracranial lesions successfully treated with unrelated cord blood transplantation. Case Rep Hematol. 2015;2015:610581.

https://doi.org/10.1155/2015/610581

2. Orbach D, Sarnacki S, Brisse HJ, Gauthier-Villars M, Jarreau PH, Tsatsaris V, Baruchel A, Zerah M, Seigneur E, Peuchmaur M, Doz F. Neonatal cancer. Lancet Oncol. 2013;14(13):e609–e620.

https://doi.org/10.1016/S1470-2045(13)70327-6

3. Mussina K, Kuanova B, Syssoyev D, Gaipov A, Poddighe D, Shaikhyzada K, Aimyshev T, Galiyeva D. Epidemiology of pediatric hematological malignancies in Kazakhstan: data from Unified National Electronic Healthcare System 2014–2021. Eur J Pediatr. 2024;183:1683–1691.

https://doi.org/10.1007/s00431-023-05412-3

4. Brown PA. Neonatal leukemia. Clin Perinatol. 2021;48(1):15–33.

https://doi.org/10.1016/j.clp.2020.11.002

5. Yang CX, Yang Y, Zhang FL, Wang DH, Bian QH, Zhou M, Zhou MX, Yang XY. Congenital leukemia: a case report and review of literature. World J Clin Cases. 2023;11(29):7227–7233.

https://doi.org/10.12998/wjcc.v11.i29.7227

6. Wertheim G. Infant acute leukemia. Clin Lab Med. 2021;41(3):541–550.

https://doi.org/10.1016/j.cll.2021.04.002

7. Gözdaşoğlu S. Infant Leukemia. Exon Publications [Internet]. 2022 October 16 [cited 2024 January 23];23–32. Available from:

https://doi.org/10.36255/exon-publications-leukemia-infant-leukemia

8. Цаур Г.А., Ригер Т.О., Попов А.М., Кустанович А.М., Ольшанская Ю.В., Наседкина Т.В., Солодовников А.Г., Шориков Е.В., Демина А.С., Плеханова О.М., Нохрина Е.С., Вержбицкая Т.Ю., Стренева О.В., Макарова О.В., Аракаев О.Р., Савельев Л.И., Алейникова О.В., Лапотентова Е.С., Мякова Н.В., Фоминых В.В., Кондратчик К.Л., Бойченко Е.Г., Пономарева Н.И., Карачунский А.И., Румянцев А.Г., Фечина Л.Г. Прогностическая роль различных перестроек 11q23/KMT2A у детей первого года жизни с острым лимфобластным лейкозом. Вопр Гематол Онкол Иммунопатол Педиатр. 2021; 20 (1): 27–39.

Tsaur G.A., Riger T.O., Popov A.M., Kustanovich A.M., Olshanskaya Yu.V., Nasedkina T.V., Solodovnikov A.G., Shorikov E.V., Demina A.S., Plekhanova O.M., Nokhrina E.S., Verzhbitskaya T.Yu., Streneva O.V., Makarova O.V., Arakaev O.R., Seveliev L.I., Aleinikova O.V, Lapotentova E.S., Myakova N.V., Fominykh V.V., Kondratchik K.L., Boichenko E.G., Ponomareva N.I., Karachunskiy A.I., Roumiantsev A.G., Fechina L.G. Prognostic significance of 11q23/KMT2A rearrangements in infants with acute lymphoblastic leukemia. Vopr Gematol Onkol Immunopatol Pediatr. 2021;20(1):27–39. Russian.

https://doi.org/10.24287/1726-1708-2021-20-1-27-39

9. Yamato G, Park MJ, Sotomatsu M, Kaburagi T, Maruyama K, Kobayashi T, Nishi A, Sameshima K, Ohki K, Hayashi Y. Clinical features of Down syndrome patients with transient abnormal myelopoiesis. Int J Hematol. 2021;113(5):662–667.

https://doi.org/10.1007/s12185-020-03066-7

10. Stam RW. The ongoing challenge of treating infant acute lymphoblastic leukemia. Haematologica. 2019;104(10):1964–1972.

https://doi.org/10.3324/haematol.2018.211300

11. Pieters R, De Lorenzo P, Ancliffe P, Aversa LA, Brethon B, Biondi A, Campbell M, Escherich G, Ferster A, Gardner RA, Kotecha RS, Lausen B, Li CK, Locatelli F, Attarbaschi A, Peters C, Rubnitz JE, Silverman LB, Stary J, Szczepanski T, Vora A, Schrappe M, Valsecchi MG. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the Interfant-06 protocol: results from an international phase III randomized study. J Clin Oncol. 2019;37(25):2246–2256.

https://doi.org/10.1200/JCO.19.00261

12. Baigutanova AN, Zhanpeissova AA, Tukbekova BT, Zhumakanova KS, Akhaeva AS. Clinical features of community-acquired pneumonia in children with iron deficiency anemia. Reprod Med Centr Asia. 2025;(2):216–223.

https://doi.org/10.37800/RM.2.2025.524

13. Ibrahimova A, Pommert L, Breese EH. Acute leukemia in infants. Curr Oncol Rep. 2021;23(3):27.

https://doi.org/10.1007/s11912-021-01021-1

14. Meyer C, Schneider B, Jakob S, Strehl S, Attarbaschi A, Schnittger S, Schoch C, Jansen MW, van Dongen JJ, den Boer ML, Pieters R, Ennas MG, Angelucci E, Koehl U, Greil J, Griesinger F, Zur Stadt U, Eckert C, Szczepański T, Niggli FK, Schäfer BW, Kempski H, Brady HJ, Zuna J, Trka J, Nigro LL, Biondi A, Delabesse E, Macintyre E, Stanulla M, Schrappe M, Haas OA, Burmeister T, Dingermann T, Klingebiel T, Marschalek R. The MLL recombinome of acute leukemias. Leukemia. 2018;32(2):273–284.

https://doi.org/10.1038/leu.2017.213

15. Ahlgren L, Pilheden M, Sturesson H, Song G, Walsh MP, Yang M, Maillard M, Zhao H, Cheng Z, Singh V, Castor A, Pronk CJ, Marquart HV, Lausen B, Schneider P, Barbany G, Pokrovskaja Tamm K, Abrahamsson J, Lohi O, Fogelstrand L, Menendez P, Pieters R, Zhang J, Lindkvist-Petersson K, Yang JJ, Gruber TA, Stam RW, Ma J, Hagström-Andersson AK. The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia. Nat Commun. 2025;16:8964.

https://doi.org/10.1038/s41467-025-64190-8

16. Stelmach P, Trumpp A. Leukemic stem cells and therapy resistance in acute myeloid leukemia. Haematologica. 2023;108(2):353–366.

https://doi.org/10.3324/haematol.2022.280800