{ "abstract": "Introduction: The prognosis of myeloid leukaemia associated with Down syndrome (ML-DS) is excellent with reduced-intensity chemotherapy; however, that of refractory or relapsed ML-DS remains dismal. These contrasting outcomes highlight the importance of risk-stratified therapy, based on reliable prognostic factors, to prevent treatment-related mortality and relapse. In addition, novel therapeutic strategies capable of overcoming the poor prognosis of high-risk patients are eagerly anticipated. Based on the results of molecular analyses, in vitro functional assays and anecdotal case reports, azacitidine (AZA), a hypomethylating agent, is a promising candidate for novel therapeutic strategies for high-risk ML-DS.\n\nMethods and analysis: In this multicentre, single-arm phase II clinical trial, the Japan Children’s Cancer Group AML-D24, we will stratify patients with newly diagnosed ML-DS according to age at diagnosis, GATA1 mutation status and treatment response. Patients <24 months of age at the diagnosis with a GATA1 mutation who achieve morphological complete remission and are negative for flow cytometric measurable residual disease at the end of induction will be classified as the low-risk (LR) group and receive less intensive chemotherapy. The other participants, stratified into the non-LR group, will be treated with AZA-combined chemotherapy. The objective of this trial is to evaluate the efficacy and safety of AZA-combined chemotherapy in children with non-LR ML-DS. The primary endpoint is the 3-year event-free survival in the non-LR group. The planned enrolment is 145 patients, including 47 non-LR patients. The study period consists of a 7-year accrual period (including an enrolment suspension period for interim analysis) followed by a 3-year follow-up period for a total duration of 10 years.\n\nEthics and dissemination: This study was approved by the National Hospital Organization Review Board for Clinical Trials (Nagoya, Japan) on 12 May 2025 and was registered in the Japan Registry of Clinical Trials ( https://jrct.mhlw.go.jp/latest-detail/jRCTs041250031 ). Written informed consent will be obtained from all patients and/or their guardians. The results of this study will be disseminated through publication in peer-reviewed journals and presentation at national and international scientific conferences.\n\nTrial registration number: jRCTs041250031.", "abstract_shown": true, "affiliations": [ "Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan", "Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan", "Center for Clinical Research and Advanced Medicine, Shiga University of Medical Science, Otsu, Japan", "Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan", "Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Aichi Medical Center Nagoya First Hospital, Nagoya, Japan", "Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan", "Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan", "Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan", "Department of Pediatrics, Ehime Prefectural Central Hospital, Matsuyama, Japan", "Department of Pediatrics, Oita University Faculty Of Medicine, Oita, Japan", "Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan", "Division of Cancer Immunodiagnostics, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan", "Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan", "Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan", "Department of Pediatrics, Kindai University Faculty of Medicine, Sakai, Japan", "Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan", "Division of Cancer Evolution, National Cancer Center Research Institute, Tokyo, Japan", "Division of Fetal Development, National Research Institute for Child Health and Development, Tokyo, Japan", "Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan", "Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan", "Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan", "Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan", "Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan" ], "article_type": null, "arxiv": null, "author_total": 24, "authors": [ { "affs": [ 0 ], "name": "Kentaro Nakashima", "orcid": "0000-0002-4633-110X" }, { "affs": [ 1 ], "name": "Daisuke Hasegawa" }, { "affs": [ 2 ], "name": "Jun Matsubayashi", "orcid": "0000-0003-4104-6833" }, { "affs": [ 3 ], "name": "Shiro Tanaka" }, { "affs": [ 4 ], "name": "Asahito Hama" }, { "affs": [ 5 ], "name": "Genki Yamato" }, { "affs": [ 6 ], "name": "Shota Kato", "orcid": "0000-0003-3656-2665" }, { "affs": [ 7 ], "name": "Mamoru Honda" }, { "affs": [ 8 ], "name": "Kozo Nagai" }, { "affs": [ 9 ], "name": "Hironori Goto" }, { "affs": [ 10 ], "name": "Shin-Ichi Tsujimoto" }, { "affs": [ 11 ], "name": "Takao Deguchi" }, { "affs": [ 12 ], "name": "Kaori Niwa" }, { "affs": [ 13, 14 ], "name": "Hidefumi Hiramatsu" }, { "affs": [ 15 ], "name": "Kiminori Terui" }, { "affs": [ 15 ], "name": "Tsutomu Toki" }, { "affs": [ 16 ], "name": "Kenichi Yoshida" }, { "affs": [ 17 ], "name": "Tomoko Kawai" }, { "affs": [ 18 ], "name": "Akiko M Saito" }, { "affs": [ 19 ], "name": "Hiroshi Moritake" }, { "affs": [ 20 ], "name": "Takashi Taga" }, { "affs": [ 21 ], "name": "Yasuhiro Okamoto" }, { "affs": [ 7 ], "name": "Katsuyoshi Koh" }, { "affs": [ 22 ], "name": "Daisuke Tomizawa" } ], "bibtex": "https://research.draconitic.com/paper/evjxw36x99190.bib", "cited_by": 0, "doi": "10.1136/bmjopen-2025-115972", "fulltext_url": null, "id": "evjxw36x99190", "issns": [ "2044-6055", "2044-6055" ], "landing_url": "https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2025-115972", "language": null, "licence": "CC-BY-NC-4.0", "licence_label": "CC BY-NC 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2720|Acute Myeloid Leukemia Research" ] ], "openalex": "W7214986798", "pdf_url": "https://bmjopen.bmj.com/content/bmjopen/16/9/e115972.full.pdf", "pmcid": null, "pmid": null, "published": "2026-09-30", "publisher": "BMJ", "ris": "https://research.draconitic.com/paper/evjxw36x99190.ris", "sources": [ { "first_seen": "2026-10-30T12:19:44Z", "native_id": "10.1136/bmjopen-2025-115972", "source": "crossref", "url": "https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2025-115972" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2720|Acute Myeloid Leukemia Research", "subfield": "general" } ], "title": "Efficacy and safety of risk-stratified chemotherapy with azacitidine for children with myeloid leukaemia with Down syndrome: protocol for a multicentre phase II trial (JCCG AML-D24)", "title_text": "Efficacy and safety of risk-stratified chemotherapy with azacitidine for children with myeloid leukaemia with Down syndrome: protocol for a multicentre phase II trial (JCCG AML-D24)", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:44Z", "url": "https://research.draconitic.com/paper/evjxw36x99190", "venue": "BMJ Open", "versions": [] }