Pediatric myelodysplastic syndrome (MDS) is a rare disorder with an annual incidence of only 2-4 per million children. It comprises a heterogeneous group of clonal stem cell disorders characterized by peripheral blood cytopenias, and ineffective and dysplastic hematopoiesis. MDS can be classified as primary de novo MDS and secondary MDS following congenital or acquired bone marrow failure (BMF) syndromes, radiation therapy, or cytotoxic therapies for both malignant and non-malignant conditions.
|Primary MDS||MDS in a first degree relative (familial MDS) All others not described below|
|Secondary MDS||Prior malignancy and/or prior chemo- or radiation therapy Known congenital bone marrow failure disorders Prior aplastic anemia|
TYPES OF PEDIATRIC MDS
The hallmark of MDS is dysplasia that can be observed in the bone marrow and peripheral blood of affected patients.
In 2008, the World Health Organization (WHO) classification of neoplastic diseases of the hematopoietic and lymphoid tissue revised the MDS classification system and acknowledged that pediatric MDS has some distinct differences from adult MDS. Therefore, the WHO added a separate category for childhood MDS. The following disease entities are described:
|Refractory cytopenia of childhood (RCC) Refractory anemia with excess blasts (RAEB) RAEB in transformation (RAEB-T)|
The specific subtype of childhood MDS is mostly defined based on the number of blasts observed in the peripheral blood and bone marrow. While RAEB is defined by 2-19% of blast in the peripheral blood and 5-19% of blast in the bone marrow, RAEB-T shows 20-29% of blasts in the blood or bone marrow. In these cases, children are often diagnosed with Acute Myeloid Leukemia (AML) where the marrow demonstrates myelodysplastic changes and often shows cytogentic changes associated with MDS.
In 2004, the European Working Group on childhood MDS (EWOG-MDS) published their findings on prospective studies of pediatric MDS and showed that about 54% of all childhood MDS are classified as Refractory Cytopenia (RC), whereas RAEB and RAEB-T only contribute 26% and 20% respectively. RC is diagnosed in all age groups and affects boys and girls with equal frequency.
MDS associated with Down syndrome is now considered a completely separate disease entity. In addition, the pediatric overlap syndromes between MDS and myeloproliferative disorders (MPD), in particular Juvenile Myelomonocytic Leukemia (JMML), are now also considered distinct disease entities and are no longer grouped together with MDS.