Pediatric myelodysplastic syndromes (MDS) comprise less than 5% of childhood malignancies. Approximately 30% to 45% of pediatric MDS cases are associated with an underlying genetic predisposition syndrome. A subset of patients present with MDS/acute myeloid leukemia (AML) following intensive chemotherapy for an unrelated malignancy. A definitive diagnosis of MDS can often only be rendered pending a comprehensive clinical and laboratory-based evaluation, which frequently includes ancillary testing in a reference laboratory. Clinical subtypes, the current diagnostic schema, and the results of more recently performed next-generation sequencing studies in pediatric MDS are discussed here.
Pediatric myelodysplastic syndrome (MDS) is rare and often develops in the setting of an underlying inherited bone marrow failure syndrome.
Refractory cytopenia of childhood and MDS with excess blasts comprise most cases.
Definitive diagnosis frequently requires repeat marrow sampling and correlation with ancillary laboratory testing.
Allogeneic hematopoietic stem cell transplant represents the only curative intervention, and should be considered in all patients based on clinical and genetic features.
Comprehensive next-generation sequencing–based studies are starting to reveal novel and unique aspects of biology in pediatric MDS.
Clinical and laboratory parameters
Approximately 20% of pediatric myelodysplastic syndrome (MDS) cases are detected incidentally on routine laboratory investigation, or during the work-up for a suspected inherited bone marrow failure (IBMF) syndrome. More frequently, patients present with symptoms related to occult cytopenias, including fatigue, fever, infection, and/or bleeding. In contrast with adults, pediatric patients with MDS more often present with bicytopenias, rather than isolated anemia. Given the association with IBMF syndromes in many cases, physical examination findings may be particularly informative, and may reveal skeletal, cutaneous, genitourinary, cardiovascular, and/or gastrointestinal anomalies. The combination of cytopenias and a hypocellular bone marrow is alone nonspecific, and therefore the following differential diagnostic considerations warrant exclusion: vitamin and/or mineral deficiencies and zinc toxicity , viral infections; toxin or drug exposures ; autoimmune and other rheumatologic disorders, such as juvenile rheumatoid arthritis; mitochondrial disorders (eg, Pearson syndrome); various metabolic disorders; inherited anemias; and IBMF syndromes.
In a recent retrospective review of laboratory data collected from 246 patients suspected of presenting with either an IBMF or MDS, the investigators analyzed morphologic, flow cytometric, karyotypic, and fluorescence in situ hybridization (FISH) data from 595 specimens (246 total patients) to evaluate their potential diagnostic utility. The number of bone marrow biopsy samples examined per patient ranged from 1 to 24 (median, 1). Interestingly, of the 595 total cases evaluated, 506 (85.0%) were associated with completely normal bone marrow examinations (ie, dysplasia <10%, normal flow cytometry results, normal karyotype, no aberrations by MDS-specific FISH studies). Out of all patients in the study, 194 (78.9%) had normal results for all of their bone marrow samples examined during the study period. Approximately 30% of the total cases ultimately had no diagnostic evidence of an IBMF syndrome, germline mutation-related syndrome, or myeloid neoplasm.