{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:02:33Z","timestamp":1782824553439,"version":"3.54.5"},"reference-count":23,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T00:00:00Z","timestamp":1726876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying effective salvage therapies for relapsed APL is crucial to improve patient outcomes. Methods: A retrospective analysis was performed on a multicentric cohort of 67 APL patients in first relapse, treated in three Italian hematology centers from June 1981 to November 2021. The overall survival (OS) and cumulative incidence of relapse (CIR) were calculated, and predictive factors were assessed using Cox regression models. Results: Overall, 61 patients (91%) received ATO \u00b1 ATRA (40.3%), chemo-based regimens (40.3%), or ATRA \u00b1 Gemtuzumab ozogamicin (GO) (10.4%). Complete remission (CR) was achieved in 98.2% of patients (molecular CR, n = 71.4%). With a median follow-up time of 54.5 months, the 5-year OS was 73% in the ATO \u00b1 ATRA group, 44% in the chemo-based group, and 29% in the ATRA \u00b1 GO group (p = 0.035). The 5-year OS rate was also higher for transplant recipients vs. non-recipients within the chemo-based cohort (50% vs. 33%, p = 0.017), but not in the ATO-based cohort (p = 0.12). ATO-based salvage therapy resulted in better OS in both univariate (p = 0.025) and multivariate analyses (p = 0.026). The 2-year CIR was higher in patients without molecular CR vs. patients in molecular CR (66% vs. 24%, p = 0.034). Molecular CR was a significant predictor of second relapse in both univariate (p = 0.035) and multivariate analyses (p = 0.036). Conclusions: Our findings support the efficacy of ATO-based therapies in first relapse of APL and confirm the achievement of molecular remission as an independent outcome predictor in both first and second APL relapse.<\/jats:p>","DOI":"10.3390\/cancers16183214","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:15:07Z","timestamp":1727082907000},"page":"3214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Response Rates and Transplantation Impact in Patients with Relapsed Acute Promyelocytic Leukemia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-2936","authenticated-orcid":false,"given":"Alessandro","family":"Costa","sequence":"first","affiliation":[{"name":"Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, 09121 Cagliari, 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, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Scalzulli","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-3051","authenticated-orcid":false,"given":"Laura","family":"Cicconi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Polo Universitario Pontino, S.M. Goretti Hospital, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-0663","authenticated-orcid":false,"given":"Luca","family":"Guarnera","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Carmosino","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3638-0650","authenticated-orcid":false,"given":"Raffaella","family":"Cerretti","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Bisegna","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saveria","family":"Capria","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Minotti","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Paola","family":"Iori","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Torrieri","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0245-0553","authenticated-orcid":false,"given":"Adriano","family":"Venditti","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7429-8004","authenticated-orcid":false,"given":"Alessandro","family":"Pulsoni","sequence":"additional","affiliation":[{"name":"Department of Hematology, Polo Universitario Pontino, S.M. Goretti Hospital, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Martelli","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-4761","authenticated-orcid":false,"given":"Maria Teresa","family":"Voso","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-6162","authenticated-orcid":false,"given":"Massimo","family":"Breccia","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.beha.2014.04.006","article-title":"Understanding the molecular pathogenesis of acute promyelocytic leukemia","volume":"27","author":"Hasan","year":"2014","journal-title":"Best Pract. Res. Clin. 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