Topics in Pediatric Leukemia -- Myelodysplastic and Myeloproliferative Disorders of Childhood

Joseph Lasky, MD; Kathleen M. Sakamoto, MD, PhD

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In This Article

Introduction

The myelodysplastic and myeloproliferative syndromes are rare in childhood, accounting for about 3% of childhood malignancies.[1] They consist of a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis; impaired maturation of hematopoietic cells; progressive cytopenias or erythro-, leuko-, or thrombocytosis; and an increased risk of developing acute myeloid leukemia (AML). Conceptually, it is helpful to consider these syndromes as part of a continuum with the myelodysplastic syndromes (MDS) on one end and the myeloproliferative syndromes (MPS) on the other, with a group of "bridging" syndromes in between.[2]

The MPS disease most commonly seen in children is the adult form of chronic myelogenous leukemia (CML) (t[9:22] or BCR/ABL containing CML). This is the subject of a separate review and is not discussed here. Other MPS seen in adults with some frequency are exceedingly rare in children, such as polycythemia vera, essential thrombocythemia, and agnogenic myeloid metaplasia. The transient myeloproliferative disorder in children with Down syndrome is a unique entity recently linked to mutations of the GATA1 transcription factor.[3]

The MDS entities of childhood can be divided into de novo (primary) forms of MDS or secondary MDS. The secondary forms are either a result of exposure to chemotherapy or radiation, secondary to a congenital or constitutional disorder (eg, Down syndrome), or the result of associated bone marrow failure syndromes (eg, Fanconi anemia). These disorders are often considered "preleukemic" conditions, and differentiating some forms of MDS from de novo AML can be difficult. Indeed, the conversion rate for the MDS conditions approaches 40%.[1] However, multiple studies have suggested that AML developing after a period of myelodysplasia may be a distinct clinicopathological entity, often with a worse prognosis than true de novo AML.[4,5,6] Although there is a close link between these 2 diseases, this review focuses on MDS as a separate classifiable disease. Classification of primary MDS in childhood mirrors that of the adult classification.

Finally, there are the bridging disorders, such as juvenile myelomonocytic leukemia (JMML), which is the most common of these disorders, although accounting only for 2% of childhood hematologic malignancies.[7] Chronic myelomonocytic leukemia (CMML) is also included in this classification, but it is exceedingly rare in children. The adult form of CMML accounts for about 16% of adult cases of MDS.[8] The pediatric incidence has not been quantified. CMML was originally grouped together with JMML, but it has recently been defined as an entity similar to the adult form of CMML, and is reserved for cases secondary to previous chemotherapy.[7]

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