{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:39:03Z","timestamp":1792931943536,"version":"4.5.0"},"reference-count":77,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:sec id=\"ab-crv230006-1\"><jats:title>Importance<\/jats:title><jats:p>Down syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recognized for decades, consisting of an approximately 150-fold higher risk of acute myeloid leukemia (AML) before age 4 years, and a 10- to 20-fold higher risk of acute lymphoblastic leukemia (ALL), compared with children without DS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-crv230006-2\"><jats:title>Observations<\/jats:title><jats:p>A recent National Institutes of Health-sponsored conference, ImpacT21, reviewed research and clinical trials in children, adolescents, and young adults (AYAs) with DS-AL and are presented herein, including presentation and treatment, clinical trial design, and ethical considerations for this unique population. Between 10% to 30% of infants with DS are diagnosed with transient abnormal myelopoiesis (TAM), which spontaneously regresses. After a latency period of up to 4 years, 20% to 30% develop myeloid leukemia associated with DS (ML-DS). Recent studies have characterized somatic mutations associated with progression from TAM to ML-DS, but predicting which patients will progress to ML-DS remains elusive. Clinical trials for DS-AL have aimed to reduce treatment-related mortality (TRM) and improve survival. Children with ML-DS have better outcomes compared with non-DS AML, but outcomes remain dismal in relapse. In contrast, patients with DS-ALL have inferior outcomes compared with those without DS, due to both higher TRM and relapse. Management of relapsed leukemia poses unique challenges owing to disease biology and increased vulnerability to toxic effects. Late effects in survivors of DS-AL are an important area in need of further study because they may demonstrate unique patterns in the setting of chronic medical conditions associated with DS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-crv230006-3\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Optimal management of DS-AL requires specific molecular testing, meticulous supportive care, and tailored therapy to reduce TRM while optimizing survival. There is no standard approach to treatment of relapsed disease. Future work should include identification of biomarkers predictive of toxic effects; enhanced clinical and scientific collaborations; promotion of access to novel agents through innovative clinical trial design; and dedicated studies of late effects of treatment.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2023.2163","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T15:07:59Z","timestamp":1689260879000},"page":"1283","source":"Crossref","is-referenced-by-count":27,"title":["Management of Down Syndrome\u2013Associated Leukemias"],"prefix":"10.1001","volume":"9","author":[{"given":"Anupam","family":"Verma","sequence":"first","affiliation":[{"name":"Pediatric Oncology Branch, Center for Cancer Research (CCR), NCI, NIH, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Lupo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology-Oncology, Baylor College 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