Refractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory cytopenia of childhood. (The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered at clinicaltrials.gov identifiers 00499070 and 00662090, respectively).

Department of Hematology University Children's Hospital Zurich Switzerland

Department of Immunology Erasmus MC Erasmus University Medical Center Rotterdam The Netherlands

Department of Immunology Erasmus MC Erasmus University Medical Center Rotterdam The Netherlands Department of Pediatric Oncology Hematology Sophia Children's Hospital Erasmus University Medical Center Rotterdam The Netherlands

Department of Pathology Clinical Centre South West Böblingen Clinics Germany

Department of Pediatric Hematology Oncology Charles University and University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology Oncology Ghent University Hospital Ghent Belgium

Department of Pediatric Hematology Oncology IRCCS Ospedale Bambino Gesù Rome University of Pavia Italy

Department of Pediatric Oncology Hematology Sophia Children's Hospital Erasmus University Medical Center Rotterdam The Netherlands

Department of Pediatrics Aarhus University Hospital Skejby Aarhus Denmark

Department of Pediatrics and Adolescent Medicine Division of Pediatric Hematology and Oncology University of Freiburg Germany

Pediatric Hematology Fondazione IRCCS Policlinico San Matteo Pavia Italy

St Anna Children's Hospital and Children's Cancer Research Institute Department of Pediatrics Medical University of Vienna Austria

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Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia

Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome

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ClinicalTrials.gov
NCT00499070, NCT00662090