Incidence, risk factors, and outcomes of second neoplasms in patients with acute promyelocytic leukemia: the PETHEMA-PALG experience

Marta Sobas (Corresponding author), Wanda Knopinska-Posluszny, Beata Piątkowska-Jakubas, Flor García-Álvarez, María Elena Amutio Díez, Mar Caballero, David Martínez-Cuadrón, Eliana Aguiar, Jose González-Campos, Ana Garrido, Lorenzo Algarra, Olga Salamero, Javier de la Serna, Maria Jose Sayas, Manuel Mateo Perez-Encinas, Susana Vives, Belén Vidriales, Jorge Labrador, Ana Inés Prado, Lucía CelebrinJiri Mayer, Joana Brioso, Almudena de Laiglesia, Juan Miguel Bergua, Maria Luz Amigo, Carlos Rodriguez-Medina, Marta Polo, Agnieszka Pluta, Edyta Cichocka, Marek Skarupski, Miguel A. Sanz, Agnieszka Wierzbowska, Pau Montesinos

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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.

Original languageEnglish
Pages (from-to)451-461
Number of pages11
JournalAnnals of Hematology
Issue number2
Publication statusPublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).


This work was partially financed with FEDER funds (CIBERONC (CB16/12/00284)) and with Instituto de Investigación Sanitaria La Fe funds (2016/0158).

FundersFunder number
Instituto de Investigación Sanitaria La Fe funds2016/0158
European Regional Development FundCB16/12/00284


    • Acute promyelocytic leukemia
    • Chemotherapy based and chemotherapy free regimens
    • Outcomes
    • Risk factors
    • Second neoplasms


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