{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:15:56Z","timestamp":1773036956491,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute promyelocytic leukemia (APL) has become a highly curable malignancy with the advent of targeted therapies. However, early death (ED), predominantly caused by severe hemorrhagic complications, continues to be the most significant obstacle to achieving high survival rates in real-world clinical practice, where outcomes often lag behind those reported in controlled trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This retrospective study aimed to identify the key clinical and laboratory factors associated with ED and overall survival (OS) in a cohort of newly diagnosed APL patients. The study also sought to evaluate the impact of current supportive care strategies and identify opportunities for improved management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center, retrospective analysis included 132 patients newly diagnosed with APL between June 2017 and January 2023. Data on demographics, baseline laboratory values, immunophenotyping, treatment, and outcomes were collected. Univariate and multivariate logistic regression analyses were used to identify independent predictors of ED, while Kaplan-Meier and Cox regression models were used to assess survival outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The ED rate was 12.88% (17 patients), with hemorrhage being the primary cause. Multivariate analysis identified three independent risk factors for ED: a high white blood cell (WBC) count (&amp;gt;201 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L), prolonged prothrombin time (PT), and CD2 positivity. While severe thrombocytopenia was common, it was not an independent predictor, likely due to an aggressive platelet transfusion policy. Elevated lactate dehydrogenase (LDH) levels were significantly associated with poorer OS. Furthermore, all relapses in the high-risk group involved the central nervous system (CNS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study found that high initial WBC count, prolonged PT, and CD2 positivity are critical independent predictors of ED in APL. The findings underscore the necessity of prompt diagnosis, risk-adapted therapy, and comprehensive multidisciplinary care, including aggressive management of coagulopathy. Enhanced CNS prophylaxis should be considered for high-risk patients to prevent relapse.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1752909","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:23:03Z","timestamp":1773033783000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Risk factors and management strategies in acute promyelocytic leukemia: a real-world single-center retrospective study"],"prefix":"10.3389","volume":"13","author":[{"given":"Yafeng","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiying","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huihui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doudou","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hunan Province Chest Hospital","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai NewCore Biotechnology Co., Ltd.","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongling","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangsen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yewei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/0092-8674(91)90113-D","article-title":"The PML-RAR\u03b1 fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR","volume":"66","author":"de The","year":"1991","journal-title":"Cell."},{"key":"B2","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/0092-8674(91)90112-C","article-title":"Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR\u03b1 with a novel putative transcription factor","volume":"66","author":"Kakizuka","year":"1991","journal-title":"PML Cell"},{"key":"B3","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1182\/blood.V72.2.567.567","article-title":"Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia","volume":"72","author":"Huang","year":"1988","journal-title":"Blood."},{"key":"B4","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1300874","article-title":"Retinoic acid and arsenic trioxide for acute promyelocytic leukemia","volume":"369","author":"Lo-Coco","year":"2013","journal-title":"N Engl J Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.1182\/blood-2007-07-102798","article-title":"Acute promyelocytic leukemia: from highly fatal to highly curable","volume":"111","author":"Wang","year":"2008","journal-title":"Blood."},{"key":"B6","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1182\/blood.2024026186","article-title":"Acute promyelocytic leukemia: long-term outcomes from the HARMONY project","volume":"145","author":"Voso","year":"2025","journal-title":"Blood."},{"key":"B7","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.ccell.2017.10.002","article-title":"Acute promyelocytic leukemia: a paradigm for oncoprotein-targeted cure","volume":"32","author":"de The","year":"2017","journal-title":"Cancer Cell."},{"key":"B8","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.blre.2017.09.001","article-title":"The global problem of early deaths in acute promyelocytic leukemia: A strategy to decrease induction mortality in the most curable leukemia","volume":"32","author":"Jillella","year":"2018","journal-title":"Blood Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1007\/s12185-024-03708-0","article-title":"Dysregulated hemostasis in acute promyelocytic leukemia","volume":"119","author":"Hisada","year":"2024","journal-title":"Int J Hematol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"S122","DOI":"10.1016\/j.htct.2024.02.020","article-title":"Causes and risk factors for early death in adult patients with acute promyelocytic leukemia: a real-life experience","volume":"46","author":"Fontes","year":"2024","journal-title":"Hematol Transfus Cell Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"169","DOI":"10.6004\/jnccn.2019.7351","article-title":"Improving outcomes of acute promyelocytic leukemia in the current era: analysis of the SEER database","volume":"18","author":"Guru Murthy","year":"2020","journal-title":"J Natl Compr Canc Netw."},{"key":"B12","doi-asserted-by":"publisher","first-page":"E370","DOI":"10.1002\/ajh.25252","article-title":"Complications and early mortality in patients with acute promyelocytic leukemia treated in California","volume":"93","author":"Ho","year":"2018","journal-title":"Am J Hematol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1182\/blood-2012-08-449918","article-title":"Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the international consortium on APL","volume":"121","author":"Rego","year":"2013","journal-title":"Blood."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1038\/leu.2017.71","article-title":"Early death rates remain high in high-risk APL: update from the Swedish acute leukemia registry 1997-2013","volume":"31","author":"Lehmann","year":"2017","journal-title":"Leukemia."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.3324\/haematol.2021.280093","article-title":"A risk score based on real-world data to predict early death in acute promyelocytic leukemia","volume":"107","author":"Osterroos","year":"2022","journal-title":"Haematologica."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5126","DOI":"10.1182\/blood-2009-07-216457","article-title":"How I treat acute promyelocytic leukemia","volume":"114","author":"Tallman","year":"2009","journal-title":"Blood."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4092","DOI":"10.3390\/cancers16234092","article-title":"Acute promyelocytic leukemia in the real world: understanding outcome differences and how we can improve Them","volume":"16","author":"Bidikian","year":"2024","journal-title":"Cancers (Basel)."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1182\/blood.2024023890","article-title":"Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia","volume":"144","author":"Koury","year":"2024","journal-title":"Blood."},{"key":"B19","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1182\/hematology.2023000477","article-title":"How to avoid early mortality in acute promyelocytic leukemia","volume":"2023","author":"Odetola","year":"2023","journal-title":"Hematology Am Soc Hematol Educ Program."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/j.leukres.2013.05.007","article-title":"Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death","volume":"37","author":"Altman","year":"2013","journal-title":"Leuk Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/leu.2011.78","article-title":"Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish adult acute leukemia registry","volume":"25","author":"Lehmann","year":"2011","journal-title":"Leukemia."},{"key":"B22","doi-asserted-by":"publisher","first-page":"762653","DOI":"10.3389\/fonc.2021.762653","article-title":"Early death and survival of patients with acute promyelocytic leukemia in ATRA plus arsenic era: a population-based study","volume":"11","author":"Zhu","year":"2021","journal-title":"Front Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1080\/10428194.2020.1742910","article-title":"An effective early death scoring system for predicting early death risk in de novo acute promyelocytic leukemia","volume":"61","author":"Cai","year":"2020","journal-title":"Leuk Lymphoma."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1182\/blood-2019-01-894980","article-title":"Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet","volume":"133","author":"Sanz","year":"2019","journal-title":"Blood."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0253-2727.2018.03.002","article-title":"Chinese guidelines for diagnosis and treatment of acute promyelocytic leukemia","year":"2018","journal-title":"Zhonghua Xue Ye Xue Za Zhi."},{"key":"B26","doi-asserted-by":"publisher","first-page":"5137","DOI":"10.1182\/blood-2010-01-266007","article-title":"de la Serna J, Milone G, et al. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome","volume":"115","author":"Sanz","year":"2010","journal-title":"Blood."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1182\/blood-2013-10-512640","article-title":"How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia","volume":"123","author":"Sanz","year":"2014","journal-title":"Blood."},{"key":"B28","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1182\/blood-2018-03-836528","article-title":"Risk-adapted treatment of acute promyelocytic leukemia: results from the international consortium for childhood APL","volume":"132","author":"Testi","year":"2018","journal-title":"Blood."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1007\/s00277-023-05422-z","article-title":"Predictors of very early death in acute promyelocytic leukemia: a retrospective real-world cohort study","volume":"102","author":"Infante","year":"2023","journal-title":"Ann Hematol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1309\/XC8P9M8NKQDT38LB","article-title":"Expression of CD2 in acute promyelocytic leukemia correlates with short form of PML-RARalpha transcripts and poorer prognosis","volume":"121","author":"Lin","year":"2004","journal-title":"Am J Clin Pathol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1111\/j.1365-2257.2005.00715.x","article-title":"CD2+ acute promyelocytic leukemia is associated with leukocytosis, variant morphology and poorer prognosis","volume":"27","author":"Kaito","year":"2005","journal-title":"Clin Lab Haematol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1080\/10428194.2020.1768386","article-title":"The prognostic value of CD2, CD4, and HLA-DR expression and FLT3-ITD mutation in adult acute promyelocytic leukemia","volume":"61","author":"Nie","year":"2020","journal-title":"Leuk Lymphoma."},{"key":"B33","doi-asserted-by":"publisher","first-page":"421906","DOI":"10.1155\/2014\/421906","article-title":"Immunophenotypes and immune markers associated with acute promyelocytic leukemia prognosis","volume":"2014","author":"Xu","year":"2014","journal-title":"Dis Markers."},{"key":"B34","first-page":"4730","article-title":"The T-lineage-affiliated CD2 gene lies within an open chromatin environment in acute promyelocytic leukemia cells","volume":"62","author":"Grimwade","year":"2002","journal-title":"Cancer Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/s41375-025-02530-9","article-title":"Distinct leukemogenic mechanism of acute promyelocytic leukemia based on genomic structure of PML: RARalpha","volume":"39","author":"Minami","year":"2025","journal-title":"Leukemia."},{"key":"B36","doi-asserted-by":"publisher","first-page":"4917","DOI":"10.2147\/OTT.S144438","article-title":"Low platelet count is potentially the most important contributor to severe bleeding in patients newly diagnosed with acute promyelocytic leukemia","volume":"10","author":"Song","year":"2017","journal-title":"Onco Targets Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1080\/09537104.2020.1799969","article-title":"Investigation of fibrinogen in early bleeding of patients with newly diagnosed acute promyelocytic leukemia","volume":"32","author":"Chu","year":"2021","journal-title":"Platelets."},{"key":"B38","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/j.1600-0609.2011.01747.x","article-title":"Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia","volume":"88","author":"Chang","year":"2012","journal-title":"Eur J Haematol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"S63","DOI":"10.1016\/S0049-3848(20)30399-6","article-title":"Advances in the management of coagulopathy in acute promyelocytic leukemia","volume":"1","author":"Sanz","year":"2020","journal-title":"Thromb Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"S82","DOI":"10.1016\/j.thromres.2018.01.041","article-title":"Mechanisms and management of coagulopathy in acute promyelocytic leukemia","volume":"1","author":"David","year":"2018","journal-title":"Thromb Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.3390\/cancers15133477","article-title":"The coagulopathy of acute promyelocytic leukemia: an updated review of pathophysiology, risk stratification, and clinical management","volume":"15","author":"Hermsen","year":"2023","journal-title":"Cancers (Basel)."},{"key":"B42","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.leukres.2010.05.022","article-title":"Significance of fibrinogen, D-dimer, and LDH levels in predicting the risk of bleeding in patients with acute promyelocytic leukemia","volume":"35","author":"Kim","year":"2011","journal-title":"Leuk Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1080\/10428194.2019.1581187","article-title":"Predictors of early hemorrhage in acute promyelocytic leukemia","volume":"60","author":"Naymagon","year":"2019","journal-title":"Leuk Lymphoma."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1007\/s00277-022-04798-8","article-title":"The evaluation of risk factors leading to early deaths in patients with acute promyelocytic leukemia: a retrospective study","volume":"101","author":"Baysal","year":"2022","journal-title":"Ann Hematol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1182\/bloodadvances.2021004789","article-title":"Characteristics and predictors of early hospital deaths in newly diagnosed APL: a 13-year population-wide study","volume":"5","author":"Gill","year":"2021","journal-title":"Blood Adv."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.3324\/haematol.2009.007872","article-title":"Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis","volume":"94","author":"Montesinos","year":"2009","journal-title":"Haematologica."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1007\/s00277-023-05154-0","article-title":"Epidemiology and early mortality patterns of acute promyelocytic leukemia in the United States","volume":"102","author":"Sharma","year":"2023","journal-title":"Ann Hematol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1080\/10428194.2021.1894651","article-title":"Early mortality and overall survival in acute promyelocytic leukemia: do real-world data match results of the clinical trials?","volume":"62","author":"Dhakal","year":"2021","journal-title":"Leuk Lymphoma."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1182\/blood-2011-04-346437","article-title":"Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid","volume":"118","author":"Park","year":"2011","journal-title":"Blood."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1038\/leu.2014.240","article-title":"Early death in acute promyelocytic leukemia (APL) in French centers: a multicenter study in 399 patients","volume":"28","author":"Rahme","year":"2014","journal-title":"Leukemia."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.3324\/haematol.10874","article-title":"Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines","volume":"92","author":"Jacomo","year":"2007","journal-title":"Haematologica."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1752909\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:23:05Z","timestamp":1773033785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1752909\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":51,"alternative-id":["10.3389\/fmed.2026.1752909"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1752909","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]},"article-number":"1752909"}}