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Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5\u2010year event\u2010free survival (EFS) and overall survival (OS) rates for the entire cohort were 72%\u00a0\u00b1\u00a08% and 77%\u00a0\u00b1\u00a07%, respectively. EFS and OS were 75%\u00a0\u00b1\u00a013% and 84%\u00a0\u00b1\u00a011%, respectively, for those receiving ALL chemotherapy alone without HSCT (n\u00a0=\u00a021).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and\/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.32552","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T08:38:28Z","timestamp":1572338308000},"page":"593-601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Mixed\u2010phenotype acute leukemia: A cohort and consensus research strategy from the Children\u2019s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-6818","authenticated-orcid":false,"given":"Etan","family":"Orgel","sequence":"first","affiliation":[{"name":"Department of Pediatrics Children's Hospital Los Angeles Los Angeles California"},{"name":"Department of Pediatrics University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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