{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:21:36Z","timestamp":1788776496900,"version":"build-2803163510"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005611","name":"University of Fukui","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005611","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. The safety of CPX-351 in Japanese patients was verified by comparing safety data from the Japanese phase 1\/2 study and the global phase 3 study. This analysis included 47 patients in the safety analysis set of the Japanese study and 153 patients who received CPX-351 and were included in the intention-to-treat analysis for the global study. In both the Japanese and global studies, the most frequent adverse events were febrile neutropenia (FN) (Japanese: 85.1%, global: 70.0%) and pneumonia (25.5% and 24.2%). Median time to occurrence was 8 and 11\u00a0days for FN, and 17 and 23\u00a0days for pneumonia. Median time to hematologic recovery was 36 and 41\u00a0days for neutrophils (&gt;\u20091000\/\u03bcL), and 36 and 44\u00a0days for platelets (&gt;\u2009100,000\/\u03bcL). In the global study, univariate analysis was performed after one cycle of induction therapy to investigate factors that delay neutrophil and platelet recovery, but no specific factors were identified. In these analyses, the pattern and frequency of adverse events were similar in Japanese and non-Japanese patients, with no need for race- or region-specific management.<\/jats:p>","DOI":"10.1007\/s12185-025-04047-4","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T14:35:54Z","timestamp":1755268554000},"page":"824-834","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Safety of liposomal daunorubicin-cytarabine (CPX-351) in secondary AML: Japanese phase 1\/2 study and global phase 3 study"],"prefix":"10.1007","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-3250","authenticated-orcid":false,"given":"Naoko","family":"Hosono","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusaku","family":"Tomiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanako","family":"Emori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Isogaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"4047_CR1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.blre.2019.04.005","volume":"36","author":"RM Shallis","year":"2019","unstructured":"Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70\u201387.","journal-title":"Blood Rev"},{"issue":"4","key":"4047_CR2","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1007\/s12185-024-03837-6","volume":"120","author":"H Yamaguchi","year":"2024","unstructured":"Yamaguchi H. Advances in pathogenesis research and challenges in treatment development for acute myeloid leukemia. Int J Hematol. 2024;120(4):414\u20136.","journal-title":"Int J Hematol"},{"issue":"2","key":"4047_CR3","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1159\/000536152","volume":"147","author":"F Wachter","year":"2024","unstructured":"Wachter F, Pikman Y. Pathophysiology of acute myeloid leukemia. Acta Haematol. 2024;147(2):229\u201346.","journal-title":"Acta Haematol"},{"issue":"31","key":"4047_CR4","doi-asserted-by":"publisher","first-page":"3641","DOI":"10.1200\/JCO.2014.60.0890","volume":"33","author":"LSG \u00d8stg\u00e5rd","year":"2015","unstructured":"\u00d8stg\u00e5rd LSG, Medeiros BC, Sengel\u00f8v H, N\u00f8rgaard M, Andersen MK, Dufva IH, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol. 2015;33(31):3641\u20139.","journal-title":"J Clin Oncol"},{"issue":"3","key":"4047_CR5","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/ajh.23908","volume":"90","author":"E Huleg\u00e5rdh","year":"2015","unstructured":"Huleg\u00e5rdh E, Nilsson C, Lazarevic V, Garelius H, Antunovic P, Rangert Derolf \u00c5, et al. Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish acute leukemia registry. Am J Hematol. 2015;90(3):208\u201314.","journal-title":"Am J Hematol"},{"issue":"9","key":"4047_CR6","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1002\/ajh.23772","volume":"89","author":"X-Q Xu","year":"2014","unstructured":"Xu X-Q, Wang J-M, Gao L, Qiu H-Y, Chen Li, Jia L, et al. Characteristics of acute myeloid leukemia with myelodysplasia-related changes: a retrospective analysis in a cohort of Chinese patients. Am J Hematol. 2014;89(9):874\u201381.","journal-title":"Am J Hematol"},{"issue":"7","key":"4047_CR7","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1182\/blood-2010-08-301713","volume":"117","author":"S Kayser","year":"2011","unstructured":"Kayser S, D\u00f6hner K, Krauter J, K\u00f6hne C-H, Horst HA, Held G, et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;117(7):2137\u201345.","journal-title":"Blood"},{"issue":"1","key":"4047_CR8","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.leukres.2008.06.028","volume":"33","author":"P Tardi","year":"2009","unstructured":"Tardi P, Johnstone S, Harasym N, Xie S, Harasym T, Zisman N, et al. In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy. Leuk Res. 2009;33(1):129\u201339.","journal-title":"Leuk Res"},{"issue":"9","key":"4047_CR9","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/j.leukres.2010.01.015","volume":"34","author":"W-S Lim","year":"2010","unstructured":"Lim W-S, Tardi PG, Dos Santos N, Xie X, Fan M, Liboiron BD, et al. Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine:daunorubicin formulation, in bone marrow xenografts. Leuk Res. 2010;34(9):1214\u201323.","journal-title":"Leuk Res"},{"issue":"26","key":"4047_CR10","doi-asserted-by":"publisher","first-page":"2684","DOI":"10.1200\/JCO.2017.77.6112","volume":"36","author":"JE Lancet","year":"2018","unstructured":"Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36(26):2684\u201392.","journal-title":"J Clin Oncol"},{"issue":"6","key":"4047_CR11","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s12185-024-03733-z","volume":"119","author":"K Usuki","year":"2024","unstructured":"Usuki K, Miyamoto T, Yamauchi T, Ando K, Ogawa Y, Onozawa M, et al. A phase 1\/2 study of NS-87\/CPX-351 (cytarabine and daunorubicin liposome) in Japanese patients with high-risk acute myeloid leukemia. Int J Hematol. 2024;119(6):647\u201359.","journal-title":"Int J Hematol"},{"issue":"1","key":"4047_CR12","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1182\/bloodadvances.2020003159","volume":"5","author":"E Chiche","year":"2021","unstructured":"Chiche E, Rahm\u00e9 R, Bertoli S, Dumas P-Y, Micol J-B, Hicheri Y, et al. Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort. Blood Adv. 2021;5(1):176\u201384.","journal-title":"Blood Adv"},{"issue":"10","key":"4047_CR13","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/s41408-021-00558-5","volume":"11","author":"C Rautenberg","year":"2021","unstructured":"Rautenberg C, St\u00f6lzel F, R\u00f6llig C, Stelljes M, Gaidzik V, Lauseker M, et al. Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia. Blood Cancer J. 2021;11(10):164.","journal-title":"Blood Cancer J"},{"issue":"4","key":"4047_CR14","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1111\/bjh.19622","volume":"205","author":"P Mehta","year":"2024","unstructured":"Mehta P, Campbell V, Maddox J, Floisand Y, Kalakonda AJM, O\u2019Nions J, et al. CREST-UK: Real-world effectiveness, safety and outpatient delivery of CPX-351 for first-line treatment of newly diagnosed therapy-related AML and AML with myelodysplasia-related changes in the UK. Br J Haematol. 2024;205(4):1326\u201336.","journal-title":"Br J Haematol"},{"issue":"21","key":"4047_CR15","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1182\/blood-2013-12-540971","volume":"123","author":"JE Lancet","year":"2014","unstructured":"Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, et al. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine\/daunorubicin, vs cytarabine\/daunorubicin in older adults with untreated AML. Blood. 2014;123(21):3239\u201346.","journal-title":"Blood"},{"key":"4047_CR16","doi-asserted-by":"crossref","unstructured":"Rondoni M, Minetto P, Puglisi B, Saraceni F, Brunetti L, Mianulli AM, et al. Late hematologic recovery after CPX-351 induction chemotherapy in AML: predictive disease and patient\u2019s factors and their impact on survival. In: 65th annual meeting of the American Society of Hematlogy; December 9\u201312, 2023; San Diego, America. Abstract 4275.","DOI":"10.1182\/blood-2023-182993"},{"issue":"13","key":"4047_CR17","doi-asserted-by":"publisher","first-page":"3457","DOI":"10.3390\/cancers15133457","volume":"15","author":"L Fianchi","year":"2023","unstructured":"Fianchi L, Guolo F, Marchesi F, Cattaneo C, Gottardi M, Restuccia F, et al. Multicenter observational retrospective study on febrile events in patients with acute myeloid leukemia treated with Cpx-351 in \u201cReal-Life\u201d: the SEIFEM experience. Cancers (Basel). 2023;15(13):3457.","journal-title":"Cancers (Basel)"},{"key":"4047_CR18","doi-asserted-by":"crossref","unstructured":"Mitchell J, Pfeiffer M, Boehmer J, Gorcsan J, Dronamraju N, Faderl S, et al. Cardiotoxicity of CPX-351 vs 7+3 in patients with untreated high-risk acute myeloid leukemia. In: 2023 American Society of Clinical Oncology (ASCO) Annual Meeting; June 2\u20136, 2023; Chicago, America. Abstract 7029.","DOI":"10.1200\/JCO.2023.41.16_suppl.7029"},{"key":"4047_CR19","doi-asserted-by":"publisher","first-page":"1347547","DOI":"10.3389\/fcvm.2024.1347547","volume":"11","author":"KJ Leger","year":"2024","unstructured":"Leger KJ, Absalon MJ, Demissei BG, Smith AM, Gerbing RB, Alonzo TA, et al. Cardiotoxicity of CPX-351 in children and adolescents with relapsed AML: a Children\u2019s Oncology Group report. Front Cardiovasc Med. 2024;11:1347547.","journal-title":"Front Cardiovasc Med."}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-04047-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-025-04047-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-04047-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:23:40Z","timestamp":1763713420000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-025-04047-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["4047"],"URL":"https:\/\/doi.org\/10.1007\/s12185-025-04047-4","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]},"assertion":[{"value":"4 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"NH reports honoraria from Abbvie Inc. and Astellas Pharma Inc. YT, NE and KI are employees of Nippon Shinyaku Co., Ltd. YT reports grant from Nippon Kayaku Co., Ltd., honoraria from Abbvie Inc., Nippon Shinyaku Co., Ltd., Astellas Pharma Inc., and Nippon Kayaku Co., Ltd.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}