Myeloid leukaemia of Down syndrome

WHO-HAEM5 keeps myeloid leukaemia associated with Down syndrome as a distinct entity, defined by trisomy 21, a GATA1 mutation and onset usually before age five, often after transient abnormal myelopoiesis in the newborn (Khoury 2022). Nearly half of the leukaemias of children with Down syndrome are acute megakaryoblastic, a rare subtype in other children; GATA1 mutations and trisomy 21 cooperate in leukaemogenesis (Critical Reviews in Oncogenesis 2011). The blasts are unusually sensitive to cytarabine and daunorubicin, so the Children's Oncology Group trial AAML0431 reduced anthracycline exposure and moved high-dose cytarabine into induction: for 204 eligible patients five-year event-free survival was 89.9 percent and overall survival 93.0 percent, while the 17 with refractory or relapsed disease had 34.3 percent overall survival; measurable residual disease by flow cytometry after the first induction cycle was highly predictive of outcome (Taub 2017).

How it differs from its parent: it is the paediatric acute myeloid leukaemia with the best outlook and the least treatment, because of drug sensitivity, but with heavy treatment-related toxicity in children with Down syndrome, so dose reduction rather than intensification is the direction; relapse, though rare, is hard to salvage.

How common: no population figure in the sources read; it accounts for a large share of leukaemia in children with Down syndrome.

Treatment: reduced-intensity chemotherapy on the AAML0431 model (cytarabine and daunorubicin-based induction with high-dose cytarabine, fewer anthracycline courses, no transplant in first remission), with measurable residual disease guiding further reduction in current trials such as the response-based trial linked here; relapsed disease has no standard (Taub 2017).