Email this article The prognostic value of FLT3-ITD in different cytogenetic and molecular genetic subgroups of pediatric acute myeloid leukemia
- Authors: Itov A.B.1,2, Olshanskaya Y.V.1, Kalinina I.I.1, Zerkalenkova E.A.1,2, Gaskova M.V.1, Kazakova A.N.1, Soldatkina O.I.1, Venyov D.A.1, Bankole V.A.1, Tsaur G.A.3,4,5, Dubrovina M.Е.1, Mikhailova E.V.1, Azatyan A.S.2, Voronin K.A.1, Plyasunova S.A.1, Popov A.M.1, Maschan M.A.1, Popa A.V.1,2, Novichkova G.A.1, Maschan A.A.1
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Affiliations:
- The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
- The N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
- Regional Children's Clinical Hospital
- Institute of Medical Cell Technologies
- Ural State Medical University
- Issue: Vol 24, No 1 (2025)
- Pages: 66-77
- Section: ORIGINAL ARTICLES
- Submitted: 29.01.2025
- Accepted: 25.02.2025
- Published: 08.07.2025
- URL: https://hemoncim.com/jour/article/view/950
- DOI: https://doi.org/10.24287/1726-1708-2025-24-1-66-77
- ID: 950
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Abstract
Internal tandem duplications in the FLT3 gene (FLT3-ITD) are common in acute myeloid leukemia (AML) in adults (25–35%) and less common in children (15–17%) and, in the absence of therapy with specific inhibitors, are predictors of a poor prognosis. However, this unfavorable impact has been demonstrated mainly in AML with a normal karyotype in the absence of mutations in the NPM1 gene, or in the presence of a combination of mutations in the NPM1 gene and FLT3-ITD with a high allele ratio (> 0.5). Our study shows a high genetic heterogeneity in the patients with FLT3-ITD and its unfavorable prognostic impact in all the AML subgroups. The presence of FLT3-ITD worsens disease outcomes in the group of patients with a normal karyotype (the 2-year event-free survival (EFS) – 32%, overall survival (OS) – 55%), irrespective of the ratio of mutated to wild-type allele and the presence of mutations in the NPM1 gene. In the group of patients with markers of a favorable prognosis, the presence of FLT3ITD was associated with reduced rates of the 2-year EFS (45%; 95% CI 26–78%) and OS (43%; 95%CI 22–83%), as well as with the resistance to FLT3 inhibitors during relapse therapy. In the groups of patients with intermediate and unfavorable risk markers, the presence of FLT3-ITD was associated with a high resistance to induction therapy (57.9% and 55%, respectively). However, the addition of FLT3 kinase inhibitors to salvage therapy and a high rate of first-line hematopoietic stem cell transplantation in combination with FLT3 inhibitors as maintenance therapy in these groups significantly improved the 2-year OS rate (68% vs 62%, respectively). The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation.
About the authors
A. B. Itov
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation; The N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
Author for correspondence.
Email: albertitov03@gmail.com
ORCID iD: 0000-0003-0098-919X
Albert B. Itov - MD in Clinical Laboratory Medicine of the Laboratory of Cytogenetics and Molecular Genetics.
1 Samory Mashela St., 117997, Moscow
Russian FederationYu. V. Olshanskaya
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: Yuliya.Olshanskaya@dgoi.ru
ORCID iD: 0000-0002-2352-7716
Moscow
Russian FederationI. I. Kalinina
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: Irina.Kalinina@dgoi.ru
ORCID iD: 0000-0002-0813-5626
Moscow
Russian FederationE. A. Zerkalenkova
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation; The N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
Email: elena.zerkalenkova@dgoi.ru
ORCID iD: 0000-0001-9634-5828
Moscow
Russian FederationM. V. Gaskova
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: marina.gaskova@dgoi.ru
ORCID iD: 0000-0002-3277-9018
Moscow
Russian FederationA. N. Kazakova
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: anna.kazakova@dgoi.ru
ORCID iD: 0000-0002-1085-4646
Moscow
Russian FederationO. I. Soldatkina
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: olga.soldatkina@dgoi.ru
ORCID iD: 0000-0001-7755-0228
Moscow
Russian FederationD. A. Venyov
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: dmitriy.venev@dgoi.ru
ORCID iD: 0000-0002-0183-1530
Moscow
Russian FederationV. A. Bankole
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: vanessa.bankole@dgoi.ru
ORCID iD: 0000-0001-9533-6583
Moscow
Russian FederationG. A. Tsaur
Regional Children's Clinical Hospital; Institute of Medical Cell Technologies; Ural State Medical University
Email: tsaur@mail.ru
ORCID iD: 0000-0002-9881-6221
Yekaterinburg
Russian FederationM. Е. Dubrovina
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: Maria.Dubrovina@dgoi.ru
ORCID iD: 0000-0001-8228-4876
Moscow
Russian FederationE. V. Mikhailova
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: ekaterina.mikhailova@dgoi.ru
ORCID iD: 0000-0002-3450-0498
Moscow
Russian FederationA. S. Azatyan
The N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
ORCID iD: 0009-0000-1239-4068
Moscow
Russian FederationK. A. Voronin
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: kirill.voronin@dgoi.ru
ORCID iD: 0000-0001-7578-9657
Moscow
Russian FederationS. A. Plyasunova
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: Svetlana.Plyasunova@dgoi.ru
ORCID iD: 0000-0002-4503-0735
Moscow
Russian FederationA. M. Popov
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: alexandr.popov@dgoi.ru
ORCID iD: 0000-0002-0889-6986
Moscow
Russian FederationM. A. Maschan
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: Michael.Maschan@dgoi.ru
Moscow
Russian FederationA. V. Popa
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation; The N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
Email: aleksandr.popa@dgoi.ru
Moscow
Russian FederationG. A. Novichkova
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: Galina.Novichkova@dgoi.ru
ORCID iD: 0000-0002-2322-5734
Moscow
Russian FederationA. A. Maschan
The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Email: Aleksey.Maschan@dgoi.ru
ORCID iD: 0000-0002-0016-6698
Moscow
Russian FederationReferences
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