ASSOCIATION BETWEEN LEUKEMIC EVOLUTION AND UNCOMMON CHROMOSOMAL ALTERATIONS IN PEDIATRIC MYELODYSPLASTIC SYNDROME

Main Article Content

Viviane Lamim Lovatel https://orcid.org/0000-0001-8493-5855
Beatriz Ferreira da Silva https://orcid.org/0000-0003-4375-9300
Eliane Ferreira Rodrigues https://orcid.org/0000-0003-0419-567X
Maria Luiza Rocha da Rosa Borges https://orcid.org/0000-0002-9910-578X
Rita de Cássia Barbosa Tavares https://orcid.org/0000-0002-9050-7918
Ana Paula Silva Bueno https://orcid.org/0000-0003-0167-2258
Elaine Sobral da Costa https://orcid.org/0000-0002-5340-5816
Terezinha de Jesus Marques https://orcid.org/0000-0001-6728-2813
Teresa de Souza Fernandez

Keywords

Pediatric myelodysplastic syndrome, uncommon chromosomal abnormalities, leukemia evolution, prognosis

Abstract

Background and objective: Pediatric myelodysplastic syndrome (pMDS) is a group of rare clonal neoplasms with a difficult diagnosis and risk of progression to acute myeloid leukemia (AML). The early stratification in risk groups is essential to choosing the treatment and indication for allogeneic hematopoietic stem cell transplantation (HSCT). According to the Revised International Prognostic Scoring System, cytogenetic analysis has demonstrated an essential role in diagnosis and prognosis. In pMDS, abnormal karyotypes are present in 30-50% of the cases.  Monosomy 7 is the most common chromosomal alteration associated with poor prognosis. However, the rarity of specific cytogenetic alterations makes its prognosis uncertain. Thus, this study aimed to describe uncommon cytogenetic alterations in a cohort of 200 pMDS patients and their association with evolution to AML. Methods: The cytogenetic analysis was performed in 200 pMDS patients by G-banding and fluorescence in situ hybridization between 2000 to 2022. Results: Rare chromosome alterations were observed in 7.5% (15/200) of the cases. These chromosome alterations were divided into four cytogenetic groups: hyperdiploidy, biclonal chromosomal alterations, translocations, and uncommon deletions, which represented 33.3%, 33.3%, 20%, and 13.3%, respectively. Most of these patients (10/15) were classified with advanced MDS (MDS-EB and MDS/AML) and the initial subtype was present in five patients (RCC). The leukemic evolution was observed in 66.66% (10/15) of the patients. Most patients had poor clinical outcomes and they were indicated for HSCT.  Conclusion: The study of uncommon cytogenetic alterations in pMDS is important to improve the prognosis and guide early indication of HSCT. 


Keywords: Pediatric MDS; Leukemic evolution; rare chromosomal altwerations; HSCT, Children

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References

1. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200-1228.
2. Hasle H. Myelodysplastic and myeloproliferative disorders of childhood. Hematology Am Soc Hematol Educ Program. 2016; 2016(1):598-604.
3. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-65.
4. Moriwaki K, Manabe A, Taketani T, et al. Cytogenetics and clinical features of pediatric myelodysplastic syndrome in Japan. Int J Hematol. 2014;100(5):478-84.
5. Bacher U, Schanz J, Braulke F, Haase D. Rare cytogenetic abnormalities in myelodysplastic syndromes. Mediterr J Hematol Infect Dis. 2015; 7:e2015034.
6. Lamim Lovatel V, Otero L, Orlando EP, et al. Clinical and Prognostic Features in a Young Adult Patient with de novo Myelodysplastic Syndrome Presenting t(11;16)(q23;q24). Mediterr J Hematol Infect Dis. 2022;14(1):e2022013.
7. Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354-65.
8. Mrózek K, Kohlschmidt J, Blachly JS, et al. Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: An Alliance study. Leukemia. 2023;37(4):788-798.
9. Platte V, Bergmann A, Hildebrandt B, et al. Clinical and Cytogenetic Characterization of Early and Late Relapses in Patients Allografted for Myeloid Neoplasms with a Myelodysplastic Component. Cancers. 2022;14(24):6244.
10. de Souza DC, Fernandez Cde S, Camargo A, et al. Cytogenetic as an important tool for diagnosis and prognosis for patients with hypocellular primary myelodysplastic syndrome. Biomed Res Int. 2014;2014:542395.
11. McGowan-Jordan J, Hastings RJ, Moore S.ISCN 2020: an International System for Human Cytogenomic Nomenclature. S Karger AG;2020.
12. Sekeres MA, Taylor J. Diagnosis and Treatment of Myelodysplastic Syndromes: A Review. JAMA. 2022;328(9):872-880.
13. 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. Lancet Haematol. 2021;8(11):e828-e839.
14. Lejman M, Chałupnik A, Chilimoniuk Z, Dobosz M. Genetic Biomarkers and Their Clinical Implications in B-Cell Acute Lymphoblastic Leukemia in Children. Int J Mol Sci. 2022;23(5):2755.
15. de Souza Fernandez T, Ornellas MH, Tavares Rde C, et al. Hyperdiploid karyotype in a child with hypocellular primary myelodysplastic syndrome. Eur J Haematol. 2003;71(5):399-401.
16. Atlas of Genetics and Cytogenetics in Oncology and Haematology in 2013. Huret JL, Ahmad M, Arsaban M, et al. Nucleic Acids Res. 2013 Jan;41(Database issue):D920-4. PMID:23161685
17. Gurnari C, Piciocchi A, Soddu S. et al. Myelodysplastic syndromes with del(5q): A real-life study of determinants of long-term outcomes and response to lenalidomide. Blood Cancer J. 2022; 12(9):132.
18. Cseh AM, Niemeyer CM, Yoshimi A, et al. Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group. Br J Haematol. 2016;172(6):930-936.
19. Waespe N, Van Den Akker M, Klaassen RJ, et al. Response to treatment with azacitidine in children with advanced myelodysplastic syndrome prior to hematopoietic stem cell transplantation. Haematologica 2016;101(12):1508-1515.
20. Han JY, Theil KS, Hoeltge G. Frequencies and characterization of cytogenetically unrelated clones in various hematologic malignancies: seven years of experiences in a single institution. Cancer Genet Cytogenet. 2006;164(2):128-32.
21. Han JY, Kim KH, Kwon HC, et al. Unrelated clonal chromosome abnormalities in myelodysplastic syndromes and acute myeloid leukemias. Cancer Genet Cytogenet. 2002;132(2):156-8.
22. Rodrigues EF, de Souza DC, Camargo A, et al. Cytogenetic biclonality in a child with hypocellular primary myelodysplastic syndrome. Cancer Genet Cytogenet. 2007; 178(1):70-2.
23. Chen J, Kao YR, Sun D, et al. Myelodysplastic syndrome progression to acute myeloid leukemia at the stem cell level. Nat Med. 2019; 25(1):103-110.
24. Koppalkar RK, Rao PS, Sandhya I, Muktha R Pai. A Rare Translocation in a Paediatric Myelodysplastic Syndrome. Journal of Clinical and Diagnostic Research. 2018;12(12): ED07-ED09.