The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.

Centro Hospitalar Săo Joăo Porto Portugal

Collegium Medicum Jagiellonian University Krakow Poland

Department of Hematology and Transplantology Gdynia Poland

Department of Hematology Blood Neoplasm and Bone Marrow Transplantation Wroclaw Medical University Wroclaw Poland

Department of Hematology Research Unit Hospital Universitario de Burgos Facultad de Ciencias de la Salud Universidad Isabel 1 Burgos Spain

Department of Mathematics and Computer Science Eindhoven University of Technology 5612 AZ Eindhoven The Netherlands

Faculty of Pure and Applied Mathematics Wrocław University of Science and Technology Wroclaw Poland

Hospital 12 de Octubre Madrid Spain

Hospital Central de Asturias Oviedo Spain

Hospital Clínico San Carlos Madrid Spain

Hospital de Cruces Barakaldo Spain

Hospital de Santa Maria Lisboa Portugal

Hospital Dr Peset Valencia Spain

Hospital General de Albacete Albacete Spain

Hospital Insular de Las Palmas Las Palmas de Gran Canaria Spain

Hospital Maciel Montevideo Uruguay

Hospital Morales Meseguer Murcia Spain

Hospital Puerta de Hierro Madrid Spain

Hospital San Pedro de Alcántara Caceres Spain

Hospital Sant Pau Barcelona Spain

Hospital Tornú Buenos Aires Argentina

Hospital U Germans Trias i Pujol ICO Badalona Spain

Hospital U Vall D'Hebron Barcelona Spain

Hospital U Virgen del Rocio Sevilla Spain

Hospital Universitario de Gran Canaria Doctor Negrin Las Palmas de Gran Canaria Spain

Hospital Universitario i Politècnico la Fe Valencia Spain

Medical University of Lodz Lodz Poland

Rydygiera Hospital Torun Poland

University Hospital Brno Masaryk University Brno Czechia

University Hospital of Salamanca Salamanca Spain

University Hospital Santiago de Compostela Spain

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