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Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib

Annals of Hematology volume 100, pages 2005–2014 (2021)Cite this article

Abstract

Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12 months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200 mg/dL and LDL > 70 mg/dL 3 months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P = 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P < 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P = 0.008; HR = 3.5; 95% CI = 1.4–8.7 and P < 0.001; HR = 4.4; 95% CI = 2–9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins.

Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.

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Acknowledgments

We are deeply grateful to the patients who participated in this study and to Emanuela Morelli for English writing assistance.

Funding

This article was carried out within the framework of the research project financed by P.O.R. SARDEGNA F.S.E. 2014–2020 - Asse III “Istruzione e Formazione, Obiettivo Tematico: 10, Obiettivo Specifico: 10.5, Azione dell’accordo fi Partenariato:10.5.12 “Avviso di chiamata per il finanziamento di Progetti di ricerca – Anno 2017”.

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Authors and Affiliations

  1. Hematology Unit, Businco Hospital, ARNAS Brotzu, Cagliari, Italy

    Giovanni Caocci, Olga Mulas, Maria Pina Simula & Giorgio La Nasa

  2. Dipartimento di Scienze Mediche e Sanità Pubblica, Università di Cagliari, Cagliari, Italy

    Giovanni Caocci, Olga Mulas & Giorgio La Nasa

  3. Hematology Unit, Azienda Unità Sanitaria Locale –IRCCS, Reggio Emilia, Italy

    Isabella Capodanno

  4. Department of Medicine, Section of Hematology, University of Verona, Verona, Italy

    Massimiliano Bonifacio & Luigi Scaffidi

  5. Hematology Unit, Cardarelli Hospital, Naples, Italy

    Mario Annunziata

  6. Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy

    Sara Galimberti & Claudia Baratè

  7. Hematology Unit, “Federico II” University of Naples, Naples, Italy

    Luigiana Luciano & Fiorenza De Gregorio

  8. Division of Hematology and BMT, University of Udine, Udine, Italy

    Mario Tiribelli & Rossella Stella

  9. Hematology Unit, Azienda Ospedaliera “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy

    Bruno Martino

  10. Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    Fausto Castagnetti & Gabriele Gugliotta

  11. Hematology Unit, University of Padova, Padua, Italy

    Gianni Binotto

  12. Hematology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy

    Patrizia Pregno & Francesca Pirillo

  13. Hematology Unit, AOU Policlinico -V. Emanuele, Rodolico Hospital, Catania, Italy

    Fabio Stagno

  14. Hematology Unit, Sant’Eugenio Hospital Tor Vergata University, Rome, Italy

    Elisabetta Abruzzese & Malgorzata Monika Trawinska

  15. Haematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy

    Monica Bocchia & Anna Sicuranza

  16. Hematology Unit, AOU Careggi, University of Florence, Florence, Italy

    Antonella Gozzini

  17. Department of Emergency and Organ Transplantation – Hematology Section, University of Bari, Bari, Italy

    Francesco Albano & Immacolata Attolico

  18. Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy

    Claudio Fozza

  19. Division of Hematology, Hematology Unit, Santa Maria Hospital, Terni, Italy

    Debora Luzi

  20. Data Center and Health Outcomes Research Unit, Italian Group for Adult Hematologic Diseases (GIMEMA), Rome, Italy

    Fabio Efficace

  21. Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Daniele Cattaneo & Alessandra Iurlo

  22. Hematology, Department of Translational and Precision Medicine, Sapienza University, Policlinico Umberto 1, Rome, Italy

    Emilia Scalzulli, Robin Foà & Massimo Breccia

Authors
  1. Giovanni Caocci
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  2. Olga Mulas
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  3. Isabella Capodanno
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  4. Massimiliano Bonifacio
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  5. Mario Annunziata
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  7. Luigiana Luciano
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  34. Robin Foà
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  35. Massimo Breccia
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  36. Giorgio La Nasa
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Contributions

GC, OM, and MB conceptualized and designed the study; GC, OM, IC, MB, MA, SG, LL, MT, FC, GB, PP, FS, EA, MB, AG, FA, CF, DL, MPS, LS, CB, FDG, RS, GG, FP, MMT, AS, DC, IA, ES, AI, RF, MB, and GLN collected and assembled the data; GC, OM, and FE performed the statistical analysis; GC wrote the manuscript; GC, OM, IC, MB, MA, SG, LL, MT, FC, GB, PP, FS, EA, MB, AG, FA, CF, DL, FE, MPS, LS, CB, FDG, RS, GG, FP, MMT, AS, DC, IA, ES, AI, RF, MB, and GLN were responsible for the final approval of the manuscript.

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Correspondence to Giovanni Caocci.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Caocci, G., Mulas, O., Capodanno, I. et al. Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib. Ann Hematol 100, 2005–2014 (2021). https://doi.org/10.1007/s00277-020-04392-w

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Keywords

  • Chronic myeloid leukemia
  • Nilotinib
  • Arterial occlusive event
  • LDL
  • Cholesterol
  • Triglycerides