{"entity":{"id":"myeloid-leukaemia-of-down-syndrome","kind":"cancer","name":"Myeloid leukaemia of Down syndrome","aka":["ML-DS","Myeloid leukemia of Down syndrome","Myeloid leukaemia associated with Down syndrome","Down syndrome acute megakaryoblastic leukaemia","DS-AMKL","Myeloid leukaemia of Down syndrome (GATA1-mutated; reduced-intensity chemotherapy)"],"tldr":"Myeloid leukaemia of Down syndrome is a form of acute myeloid leukaemia in young children with Down syndrome, driven by a GATA1 mutation on top of the extra chromosome 21 and often preceded by a transient leukaemia-like illness in the newborn. Its cells are unusually sensitive to chemotherapy, so children are cured about nine times in ten with gentler treatment than other childhood leukaemia.","summary":"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).\n\nHow 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.\n\nHow common: no population figure in the sources read; it accounts for a large share of leukaemia in children with Down syndrome.\n\nTreatment: 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).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Transient_myeloproliferative_disease","links":[{"label":"NCI PDQ: childhood acute myeloid leukaemia treatment","url":"https://www.cancer.gov/types/leukemia/patient/child-aml-treatment-pdq"},{"label":"Khoury 2022, Leukemia: the 5th edition WHO classification of haematolymphoid tumours, myeloid and histiocytic neoplasms","url":"https://doi.org/10.1038/s41375-022-01613-1"},{"label":"Taub 2017, Blood: improved outcomes for myeloid leukaemia of Down syndrome, COG AAML0431","url":"https://doi.org/10.1182/blood-2017-01-764324"},{"label":"Critical Reviews in Oncogenesis 2011: myeloid leukaemia in Down syndrome","url":"https://doi.org/10.1615/critrevoncog.v16.i1-2.40"}],"tags":["subtype-page","wave4","haematologic","rare"],"related":["aml-paediatric","aml","childhood-cancers","mixed-phenotype-acute-leukaemia"],"cancers":[],"sections":[],"technologies":["mrd-testing"],"targets":["gata1"],"drugs":["cytarabine","daunorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02521493"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Children with Down syndrome have a much higher risk of leukaemia than other children, and nearly half of their leukaemias are acute megakaryoblastic (Critical Reviews in Oncogenesis 2011); the COG AAML0431 trial enrolled 204 eligible patients (Taub 2017). No population figure is in the sources read.","subtypes":["Myeloid leukaemia of Down syndrome, megakaryoblastic (the usual form)","Myeloid leukaemia of Down syndrome with prior transient abnormal myelopoiesis","Myelodysplasia-related presentation of myeloid leukaemia of Down syndrome","Refractory or relapsed myeloid leukaemia of Down syndrome (poor outlook)"],"biomarkers":["Trisomy 21 with somatic GATA1 mutation","Megakaryoblastic morphology and markers (CD41, CD61)","Measurable residual disease by flow cytometry on day 28 of induction","History of transient abnormal myelopoiesis"],"standardOfCare":[{"setting":"Newly diagnosed","approach":"Reduced-intensity cytarabine and daunorubicin-based chemotherapy on the AAML0431 model, with measurable residual disease guiding further reduction; no transplant in first remission.","refs":["cytarabine","daunorubicin","mrd-testing","aml-paediatric","nct02521493"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"aml-paediatric"},"route":"/cancers/myeloid-leukaemia-of-down-syndrome/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"mixed-phenotype-acute-leukaemia","kind":"cancer","name":"Mixed-phenotype acute leukaemia","route":"/cancers/mixed-phenotype-acute-leukaemia/"}],"technology":[{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"target":[{"id":"gata1","kind":"target","name":"GATA1","route":"/targets/gata1/"}],"drug":[{"id":"cytarabine","kind":"drug","name":"Cytarabine","route":"/drugs/cytarabine/"},{"id":"daunorubicin","kind":"drug","name":"Daunorubicin","route":"/drugs/daunorubicin/"}],"trial":[{"id":"nct02521493","kind":"trial","name":"Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome","route":"/trials/nct02521493/"}]}}