{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:05:05Z","timestamp":1790831105534,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82141125"],"award-info":[{"award-number":["82141125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["21Y31900302"],"award-info":[{"award-number":["21Y31900302"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["24Y12800602"],"award-info":[{"award-number":["24Y12800602"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008750","name":"Shanghai Municipal Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC12019121"],"award-info":[{"award-number":["SHDC12019121"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2705003"],"award-info":[{"award-number":["2022YFC2705003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2706301"],"award-info":[{"award-number":["2023YFC2706301"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This retrospective secondary analysis of the multicenter randomized CALS III\u2010AML18 trial evaluated the efficacy and safety of low\u2010dose chemotherapy (LDC) compared with standard\u2010dose chemotherapy (SDC) in children with M2 acute myeloid leukemia (AML\u2010M2). A total of 221 children were included, with 109 in the LDC arm and 112 in the SDC arm. The complete remission (CR)\/CR with incomplete recovery (CRi) rates after induction I and II were 67.0% versus 70.5% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.568) and 84.4% versus 89.3% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.740), respectively. The 3\u2009year overall survival (OS) rates were 81.2%\u2009\u00b1\u20093.9% and 86.9%\u2009\u00b1\u20093.3% in the LDC and SDC arms, respectively (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.304). The corresponding 3\u2009year relapse\u2010free survival (RFS) rates were 82.0%\u2009\u00b1\u20093.8% and 88.1%\u2009\u00b1\u20093.1% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.205), and the 3\u2009year event\u2010free survival (EFS) rates were 62.1%\u2009\u00b1\u20094.8% and 70.8%\u2009\u00b1\u20094.4% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.218). Among patients with KIT mutations, outcomes were poorer in the LDC arm than in the SDC arm, including 3\u2009year OS (67.1%\u2009\u00b1\u20098.7% vs. 91.5%\u2009\u00b1\u20094.1%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.011), RFS (70.6%\u2009\u00b1\u20097.8% vs. 87.5%\u2009\u00b1\u20094.8%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.038), and EFS (49.2%\u2009\u00b1\u20098.7% vs. 81.0%\u2009\u00b1\u20095.7%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002). Among patients who developed sepsis, grade 3\u20135 events were less frequent in the LDC arm than in the SDC arm (33.3% vs. 78.8%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). LDC was also associated with faster neutrophil and platelet recovery, lower transfusion requirements, and reduced treatment costs during induction. No statistically significant differences in remission or survival outcomes were observed between LDC and SDC, while the LDC regimen showed a lower treatment\u2010related burden. These findings support further evaluation of LDC as a toxicity\u2010sparing induction strategy in selected pediatric patients with AML\u2010M2. The poorer outcomes observed among patients with KIT mutations warrant caution when considering treatment de\u2010intensification in this subgroup.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72349","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:51:08Z","timestamp":1790830268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low\u2010Dose Cytarabine Plus G\u2010\n                    <scp>CSF<\/scp>\n                    Induction in Pediatric\n                    <scp>M2<\/scp>\n                    Acute Myeloid Leukemia: A Multicenter Study"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9929-5619","authenticated-orcid":false,"given":"Wenxin","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Fudan University, National Children's Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Fudan University, National Children's Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0831-9641","authenticated-orcid":false,"given":"Hongsheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Fudan University, National Children's Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4552-0785","authenticated-orcid":false,"given":"Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Guangzhou Women and Children's Medical Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"An","sequence":"additional","affiliation":[{"name":"Department of Hematology Xuzhou Children's Hospital, Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-6790","authenticated-orcid":false,"given":"Xiaojun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Anhui Medical University Second Affiliated Hospital  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixia","family":"Luo","sequence":"additional","affiliation":[{"name":"Children's Hospital of Kaifeng City  Kaifeng City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-2626","authenticated-orcid":false,"given":"Qian\u2010Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"China National Center for Bioinformation Beijing Institute of Genomics, Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-1209","authenticated-orcid":false,"given":"Minghua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Third Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-7930","authenticated-orcid":false,"given":"Peifang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangchun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9188-9236","authenticated-orcid":false,"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"Medical Center of Hematology Xinqiao Hospital, Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9956-5647","authenticated-orcid":false,"given":"Raul C.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-6957","authenticated-orcid":false,"given":"Shaoyan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3505-0302","authenticated-orcid":false,"given":"Xiaowen","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Children's Hospital of Fudan University, National Children's Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"3","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11030504","article-title":"Pediatric Acute Myeloid Leukemia\u2010Past, Present, and Future","volume":"11","author":"Reinhardt D.","year":"2022","journal-title":"Journal of Clinical Medicine"},{"issue":"12","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1182\/blood.2021011694","article-title":"How I Treat Pediatric Acute Myeloid Leukemia","volume":"138","author":"Rubnitz J. E.","year":"2021","journal-title":"Blood"},{"issue":"6","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.30584","article-title":"Children's Oncology Group's 2023 Blueprint for Research: Myeloid Neoplasms","volume":"70","author":"Cooper T. M.","year":"2023","journal-title":"Pediatric Blood & Cancer"},{"issue":"16","key":"e_1_2_13_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15164171","article-title":"Risk\u2010Stratified Therapy for Pediatric Acute Myeloid Leukemia","volume":"15","author":"Tomizawa D.","year":"2023","journal-title":"Cancers"},{"issue":"3","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/nsr\/nwz006","article-title":"Ecological Principle Meets Cancer Treatment: Treating Children With Acute Myeloid Leukemia With Low\u2010Dose Chemotherapy","volume":"6","author":"Hu Y.","year":"2019","journal-title":"National Science Review"},{"issue":"7","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1182\/bloodadvances.2020003453","article-title":"Minimally Myelosuppressive Regimen for Remission Induction in Pediatric AML: Long\u2010Term Results of an Observational Study","volume":"5","author":"Hu Y.","year":"2021","journal-title":"Blood Advances"},{"issue":"1","key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1182\/blood.2025030972","article-title":"A Low\u2010 Versus Standard\u2010Dose Regimen as Induction for Pediatric AML: A Multicenter, Randomized Noninferiority Trial","volume":"148","author":"Gao L.","year":"2026","journal-title":"Blood"},{"issue":"1","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1038\/s41467-022-29336-y","article-title":"Distinct Genomic Landscape of Chinese Pediatric Acute Myeloid Leukemia Impacts Clinical Risk Classification","volume":"13","author":"Liu T.","year":"2022","journal-title":"Nature Communications"},{"issue":"4","key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0145-2126(93)90026-H","article-title":"Acute Myeloblastic Leukemia (ANLL\u2010M2) With t(8;21)(q22;q22) Variant Expressing Lymphoid but Not Myeloid Surface Antigens With a High Number of G\u2010CSF Receptors","volume":"17","author":"Tsuchiya H.","year":"1993","journal-title":"Leukemia Research"},{"issue":"8","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1056\/NEJMoa025406","article-title":"Effect of Priming With Granulocyte Colony\u2010Stimulating Factor on the Outcome of Chemotherapy for Acute Myeloid Leukemia","volume":"349","author":"L\u00f6wenberg B.","year":"2003","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12935-015-0272-3","article-title":"Treatment With G\u2010CSF Reduces Acute Myeloid Leukemia Blast Viability in the Presence of Bone Marrow Stroma","volume":"15","author":"Nomdedeu M.","year":"2015","journal-title":"Cancer Cell International"},{"issue":"27","key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1200\/JCO.2006.06.5037","article-title":"Less Toxicity by Optimizing Chemotherapy, but Not by Addition of Granulocyte Colony\u2010Stimulating Factor in Children and Adolescents With Acute Myeloid Leukemia: Results of AML\u2010BFM 98","volume":"24","author":"Creutzig U.","year":"2006","journal-title":"Journal of Clinical Oncology"},{"issue":"3","key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1182\/blood-2006-07-035915","article-title":"Prophylactic Human Granulocyte Colony\u2010Stimulating Factor After Induction Therapy in Pediatric Acute Myeloid Leukemia","volume":"109","author":"Lehrnbecher T.","year":"2007","journal-title":"Blood"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","DOI":"10.1038\/bcj.2015.110","article-title":"Infectious Complications in Children With Acute Myeloid Leukemia: Decreased Mortality in Multicenter Trial AML\u2010BFM 2004","volume":"6","author":"Bochennek K.","year":"2016","journal-title":"Blood Cancer Journal"},{"key":"e_1_2_13_16_1","article-title":"Clinical Profiling of AML1:ETO and KIT Exon 17 Mutation in Pediatric AML by High\u2010Throughput Drug Sensitivity","author":"Hu Z.","year":"2026","journal-title":"BMC Cancer"},{"issue":"1","key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41408-023-00941-4","article-title":"Risk\u2010Directed Therapy Based on Genetics and MRD Improves the Outcomes of AML1\u2010ETO\u2010Positive AML Patients, a Multi\u2010Center Prospective Cohort Study","volume":"13","author":"Xu D.","year":"2023","journal-title":"Blood Cancer Journal"},{"issue":"1","key":"e_1_2_13_18_1","doi-asserted-by":"crossref","DOI":"10.1007\/s12672-026-05009-w","article-title":"Overexpression of TREM1 Predicts Poor Prognosis and Chemotherapy Resistance in Egyptian Acute Myeloid Leukemia Associated With FLT3 Internal Tandem Duplication and CD123 Expression and Stemness Signatures","volume":"17","author":"Mansor S. G.","year":"2026","journal-title":"Discover Oncology"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72349","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.72349","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:51:25Z","timestamp":1790830285000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.72349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":17,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/cam4.72349"],"URL":"https:\/\/doi.org\/10.1002\/cam4.72349","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"assertion":[{"value":"2026-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72349"}}