IMPACT ON LEUKEMIC TRANSFORMATION OF HYPERDIPLOID KARYOTYPE IN PEDIATRIC MYELODYSPLASTIC SYNDROME

Abstract

Introduction: Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal hematopoietic stem cell diseases. MDS is characterized by bone marrow dysplasias, peripheral blood cytopenias, and has an increased risk of progression to acute myeloid leukemia (AML). MDS mainly affects elderly patients over 65 years of age and it is rare in childhood. Clonal cytogenetic alterations are found in 30-70% of cases. The most frequent chromosomal abnormalities in pediatric MDS are alterations on chromosome 7 [-7/del(7q)]. Given the importance of karyotype in the prognosis of patients with MDS, it has been incorporated into prognostic risk systems. The most recent is the Revised International Prognostic Scoring System (IPSS-R). Karyotype is classified into five prognostic risk groups according to the IPSS-R: very good, good, intermediate, poor, and very poor. Hyperdiploidy is considered a rare karyotype in pediatric MDS. Therefore, its prognostic impact has not yet been elucidated. Objective: To report hyperdiploid karyotypes in children with MDS and their impact on the progression from MDS to AML. Material and methods: This study included five pediatric patients with MDS in a cohort of 200 patients. Chromosomal and clinical studies were performed between 2000-2023. Cytogenetic analyses were performed on bone marrow cells by G-banding and fluorescence in situ hybridization (FISH) according to the International System for Human Cytogenomic Nomenclature (2020). Results: The frequency of hyperdiploid karyotype was 2.5% of all cytogenetically analyzed cases (5/200). This chromosomal pattern was divided into two groups: patients with only chromosomal gains (3/5) and patients with structural alteration (2/5). The structural alterations associated with hyperdiploidy were: dup(1q) (one patient), der(6)del(6)(q21) and der(12)del(12)(p11) (one patient). Most of these patients had advanced subtypes with severe pancytopenia and hypocellular BM. All of these patients were indicated for allogeneic hematopoietic stem cell transplantation (HSCT), but four progressed to AML and three died before HSCT. Only two patients underwent HSCT; the patient with the initial subtype responded well to HSCT and is still alive. The patient with hyperdiploidy and structural alteration had cytogenetic and clinical relapse after HSCT and died. Discussion: Hyperdiploidy can be divided into two main subtypes: high hyperdiploidy (51-65 chromosomes) associated with favorable prognosis, and low hyperdiploidy (47-50 chromosomes) related to unfavorable prognosis in acute leukemias of childhood. In MDS, the hyperdiploid karyotype is rare. In this study, we describe 5 cases of hyperdiploid karyotype. According to the IPSS-R, hyperdiploid karyotypes are classified into the group of poor and very poor prognosis (three or more chromosomal alterations). In our study, hyperdiploidy was observed in the initial subtype and advanced subtypes. However, HSCT was successful only in the patient presenting the initial subtype. Conclusion: Hyperdiploid karyotype is a rare cytogenetic event in pediatric MDS. This karyotypic pattern was mainly associated with advanced subgroups and progression to AML. Our results suggest that hyperdiploidy in pediatric MDS is a predictive marker of leukemic progression and can be used to indicate these patients for HSCT, the only potentially curative treatment for patients with MDS. Supported by: : Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ (E-26/201.2018/2022).