Optimizing therapy for myeloid disorders of Down syndrome

Summary Children with Down syndrome (DS) are at increased risk of leukaemia. Myeloid disorders include transient abnormal myelopoiesis (TAM), myelodysplasia (MDS) and acute myeloid leukaemia (AML). Mutations in the GATA‐1 gene, which encodes for a transcription factor central to the normal development of the erythroid and megakaryocytic lineages, are found in cases of TAM, MDS and AML in DS children. DS children with MDS/AML mostly present between the ages of 1 and 4 years, and have a large predominance of megakaryoblastic disease (French–American–British type M7). The MDS and AML are part of a single disease entity (myeloid leukaemia of Down syndrome) that is extremely sensitive to chemotherapy. Resistant disease and relapse are rare, but treatment‐related toxicity is high, and deaths in remission have exceeded those due to disease in most series. Accordingly, controlled dosage reduction is the focus of contemporary treatment studies.