{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T14:18:46Z","timestamp":1788013126401,"version":"build-2784847793"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    All\u2010trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) has become the international standard of care for newly diagnosed acute promyelocytic leukemia (APL), demonstrating superior efficacy and safety over ATRA\u2013chemotherapy regimens. However, in Japan, ATO has been approved only for relapsed\/refractory APL, and prospective data on its frontline use are lacking. We conducted FBMTG\u2010APL2017, a prospective multicenter phase II trial in Japan, to evaluate ATRA\u2013ATO in newly diagnosed APL patients, including both low\u2013intermediate\u2010risk and high\u2010risk groups. Eighty\u2010one patients were enrolled between 2017 and 2021 and treated with ATRA plus delayed ATO during induction, followed by four cycles of ATRA\u2013ATO consolidation. Complete remission was achieved in 95.1% of patients. With a median follow\u2010up of 55\u2009months, 3\u2010year disease\u2010free survival (DFS) and overall survival (OS) were 93.6% and 95.0%, respectively, consistent with international ATRA\u2013ATO trials. DFS was 96.9% in low\u2013intermediate\u2010risk and 80.0% in high\u2010risk patients, with no significant difference. Molecular remission was achieved in 99% after consolidation, and only two molecular relapses occurred. Differentiation syndrome developed in 56.8% but was generally manageable, with only one fatal case; early death occurred in 4.9%, comparable to international data. These results provide the first prospective evidence in Japan that frontline\n                    <jats:italic>chemo\u2010free<\/jats:italic>\n                    ATRA\u2013ATO is highly effective and safe across all risk groups. They support its adoption as a new standard therapy and bridge the gap with established global practice.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Japan Registry of Clinical Trials: jRCTs071180040\n                  <\/jats:p>","DOI":"10.1111\/cas.70328","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T23:03:42Z","timestamp":1769036622000},"page":"1117-1123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Frontline\n                    <scp>ATRA<\/scp>\n                    \u2010\n                    <scp>ATO<\/scp>\n                    Therapy for Acute Promyelocytic Leukemia in Japan: Results From the Prospective Multicenter\n                    <scp>FBMTG<\/scp>\n                    \u2010\n                    <scp>APL2017<\/scp>\n                    Trial"],"prefix":"10.1111","volume":"117","author":[{"given":"Ken","family":"Takase","sequence":"first","affiliation":[{"name":"Department of Hematology and Clinical Research Institute NHO Kyushu Medical Center  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Kamimura","sequence":"additional","affiliation":[{"name":"Department of Hematology Harasanshin Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Kuriyama","sequence":"additional","affiliation":[{"name":"Department of Hematology Hamanomachi Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Tokuyama","sequence":"additional","affiliation":[{"name":"Department of Hematology Matsuyama Red Cross Hospital  Matsuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideho","family":"Henzan","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine Fukuoka Red Cross Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikane","family":"Kikushige","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilseung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Cell Therapy NHO Kyushu Cancer Center  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Mary's Hospital, Our Lady of the Snow Social Medical Corporation  Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Hematology Aiiku Hospital  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuki","family":"Ohya","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine Kurume University Hospital  Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Miyazaki Prefectural Miyazaki Hospital  Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yonemoto","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Health Sciences, Faculty of Medicine University of the Ryukyus  Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mine","family":"Harada","sequence":"additional","affiliation":[{"name":"Karatsu Higashimatsuura Medical Center  Karatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-1594","authenticated-orcid":false,"given":"Toshihiro","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medicine  Fukuoka Japan"},{"name":"Department of Hematology, Faculty of Medicine Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V72.2.567.567"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1300874"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00193-X"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.1982"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-00535"},{"key":"e_1_2_12_7_1","volume-title":"Japanese Guidelines for the Management of Hematopoietic Malignancies","author":"Japanese Society of Hematology","year":"2024"},{"issue":"4","key":"e_1_2_12_8_1","first-page":"1247","article-title":"Definition of Relapse Risk and Role of Nonanthracycline Drugs for Consolidation in Patients With Acute Promyelocytic Leukemia: A Joint Study of the PETHEMA and GIMEMA Cooperative Groups","volume":"96","author":"Sanz M. A.","year":"2000","journal-title":"Blood"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176350951"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-020-02911-z"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.1533"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030624"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-025-02530-9"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-161000"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-05-851824"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70328","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70328","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:27:35Z","timestamp":1775122055000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/cas.70328"],"URL":"https:\/\/doi.org\/10.1111\/cas.70328","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}