Is it leukemia? Hematological disorders in pediatric patients with Down syndrome — case report and literature review

Introduction: Down syndrome (DS) is the most common chromosomal aberration. DS is characterized by a higher incidence of many disorders, including those involving the haematopoietic system. The risk of developing acute myeloid leukaemia is up to 150 times higher in this group. Also, characteristic is the presence of transient abnormal myelopoiesis (TAM), which can precede the development of malignancy. These phenomena are primarily associated with mutation of the GATA1 gene, cohesin complex and signalling pathways genes, as well as overactivity of foetal liver stromal cells and intensification of inflammation, stimulating the expansion of blastic cells. Case report: A 15-month-old patient diagnosed with DS was admitted to the Clinic for diagnosis of neutropenia and thrombocytopenia. The myelogram showed no features of proliferative disease; however, TAM was suspected based on the bone marrow biopsy result. Six months later, based on the evaluation of the myelogram and immunophenotype of tumour cells, myeloid leukaemia (ML-DS) with megakaryoblastic differentiation was diagnosed. Genetic testing revealed a mutation in the GATA1 gene. The girl was qualified for treatment according to the AML-BFM 2019-ML-DS Protocol. The treatment was carried out as planned and the patient has achieved remission. Conclusions: The pathogenesis of myelopoietic disorders in children with DS is mainly due to a cascade of mutations and genetic abnormalities. For this reason, DS patients must have appropriate molecular testing and regular haematologic follow-up to closely observe the evolution of myelopoietic disorders.