{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:06:53Z","timestamp":1792325213056,"version":"4.4.0"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>All\u2010<jats:italic>trans<\/jats:italic>\u2010retinoic acid (ATRA) and arsenic trioxide (ATO) represent the standard of care for low\u2010intermediate risk acute promyelocytic leukaemia (APL). Leucocytosis during induction with ATRA\u2010ATO represents a common complication with an incidence of up to 60%. To identify predictive factors for this complication, we studied a cohort of 65 low\u2010intermediate risk APL patients treated with ATRA\u2010ATO in three highly specialized Italian centres. Overall, 39\/65 (60%) patients developed leucocytosis, with a peak in leucocyte count being most frequent in the second week from diagnosis. All cases were successfully managed with hydroxyurea. Predictive factors for leucocytosis in univariate analysis were lower platelet counts (odds ratio [OR] 0.98, 0.97\u20131.00, <jats:italic>p<\/jats:italic>\u2009=\u20090.018), lower fibrinogen levels (OR 0.36, 0.17\u20130.66, <jats:italic>p<\/jats:italic>\u2009=\u20090.003), higher bone marrow blast infiltration (OR 1.03, 1.01\u20131.07, <jats:italic>p<\/jats:italic>\u2009=\u20090.021) and CD117 expression by flow (OR 1.04, 1.01\u20131.08, <jats:italic>p<\/jats:italic>\u2009=\u20090.012). Multivariate analysis confirmed lower levels of fibrinogen at diagnosis as the strongest predictive factor for the development of leucocytosis (OR 0.36, 0.15\u20130.72, <jats:italic>p<\/jats:italic>\u2009=\u20090.009). Differentiation syndrome (DS) occurred only in patients developing leucocytosis showing a strict correlation with rising leucocytes counts (16\/39 vs. 0\/26, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In addition, other treatment\u2010related complications including QTc prolongation, cardiac events, liver, and haematological toxicities were significantly more frequent in patients experiencing leucocytosis (22\/39 vs. 3\/26, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In conclusion, APL patients undergoing ATRA\u2010ATO therapy with lower fibrinogen levels and platelet counts at diagnosis and with a massive bone marrow blast infiltrate should be carefully monitored for the development of leucocytosis during induction. DS and other treatment\u2010related complications seem to occur almost exclusively in patients developing leucocytosis, who should necessarily receive DS prophylaxis and more intensive monitoring and supportive therapy to prevent treatment complications.<\/jats:p>","DOI":"10.1111\/bjh.19759","type":"journal-article","created":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T04:30:04Z","timestamp":1726288204000},"page":"1727-1733","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Leucocytosis during induction therapy with all\u2010<i>trans<\/i>\u2010retinoic acid and arsenic trioxide in acute promyelocytic leukaemia predicts differentiation syndrome and treatment\u2010related complications"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-3051","authenticated-orcid":false,"given":"Laura","family":"Cicconi","sequence":"first","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialaura","family":"Bisegna","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine University \"La Sapienza\"  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-5544","authenticated-orcid":false,"given":"Carmelo","family":"Gurnari","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention University of Rome Tor Vergata  Rome Italy"},{"name":"Department of Translational Hematology and Oncology Research Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fanciullo","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Piciocchi","sequence":"additional","affiliation":[{"name":"GIMEMA Foundation  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Marsili","sequence":"additional","affiliation":[{"name":"GIMEMA Foundation  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Minotti","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine University \"La Sapienza\"  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Scalzulli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine University \"La Sapienza\"  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Mandelli","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Guarnera","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention University of Rome Tor Vergata  Rome Italy"},{"name":"Department of Translational Hematology and Oncology Research Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elettra","family":"Ortu\u00a0La\u00a0Barbera","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mecarocci","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Biagi","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Cenfra","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Corbingi","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Scerpa","sequence":"additional","affiliation":[{"name":"Department of Hematology, SM Goretti Hospital University Polo Pontino  Latina 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