Myeloid Proliferation Associated with Down Syndrome (ML-DS, TAM)

Children with Down syndrome have a high risk to develop transient abnormal myelopoiesis (TAM) characterized by dysplastic changes in peripheral blood. This myeloproliferative disorder is caused by a mutation in the hematopoietic transcription factor GATA1, which is strongly associated with Down syndrome. Despite spontaneous remission without therapy within the first 3 months in most patients, serious complications occur in 5–10% of patients resulting in death, usually caused by liver infiltration and subsequent liver and organ failure. Another 16–23% of patients progress to acute myeloid leukemia (myeloid proliferation associated with Down syndrome [ML-DS]) within the first 4 years of life. Patients with ML-DS have a good prognosis due to high sensitivity of the leukemic blasts to cytarabine and anthracyclines. However, therapy-related mortality remains high. In addition, relapse is associated with a very poor prognosis. Therefore, optimal therapy intensity is crucial to balance the complication rate and prognosis in these patients. The objective of current research is to establish a successful risk stratification to identify prognostic factors and patient groups who are eligible for intensity-reduced treatments.