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Second cancers in MPN: Survival analysis from an international study
Authors:Monia Marchetti  Arianna Ghirardi  Arianna Masciulli  Alessandra Carobbio  Francesca Palandri  Nicola Vianelli  Elena Rossi  Silvia Betti  Ambra Di Veroli  Alessandra Iurlo  Daniele Cattaneo  Guido Finazzi  Massimiliano Bonifacio  Luigi Scaffidi  Andrea Patriarca  Elisa Rumi  Ilaria Carola Casetti  Clemency Stephenson  Paola Guglielmelli  Elena Maria Elli  Miroslava Palova  Davide Rapezzi  Daniel Erez  Montse Gomez  Kai Wille  Manuel Perez-Encinas  Francesca Lunghi  Anna Angona  Maria Laura Fox  Eloise Beggiato  Giulia Benevolo  Giuseppe Carli  Rossella Cacciola  Mary Frances McMullin  Alessia Tieghi  Valle Recasens  Susanne Isfort  Fabrizio Pane  Valerio De Stefano  Martin Griesshammer  Alberto Alvarez-Larran  Alessandro Maria Vannucchi  Alessandro Rambaldi  Tiziano Barbui
Institution:1. Oncology Unit, Cardinal Massaia Hospital, Asti, Italy;2. FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy;3. Institute of Hematology “L. and A. Seràgnoli”, S. Orsola-Malpighi Hospital, Bologna, Italy;4. Institute of Hematology, Catholic University, Rome, Italy;5. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;6. Rete Laziale MPN, Rome, Italy;7. Division of Hematology, Foundation IRCCS Caʼ Granda Ospedale Maggiore Policlinico, and University of Milan, Milan, Italy;8. Division of Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy;9. Department of Medicine, Section of Hematology, University of Verona, Verona, Italy;10. Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy;11. Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo Pavia, Pavia, Italy;12. Department of Molecular Medicine, University of Pavia, Pavia, Italy;13. Guyʼs and St Thomasʼ NHS Foundation Trust, London, UK;14. CRIMM-Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy;15. Division of Hematology, Ospedale San Gerardo, ASST, Monza, Italy;16. Department of Hemato-oncology, University Hospital Olomouc, Olomouc, Czech Republic;17. S.C. Ematologia, Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy;18. Hematology Institute and Blood Bank, Meir Medical Center, Kfar Saba, Israel

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;19. Department of Hematology, Hospital Clínico Universitario, Valencia, Spain;20. University Clinic for Hematology and Oncology Minden, University of Bochum, Minden, Germany;21. Deparment of Hematology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain;22. Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy;23. Department of Hematology, Hospital del Mar, Barcelona, Spain;24. Department of Hematology, Hospital Universitario Vall dʼHebron, Barcelona, Spain;25. Unit of Hematology, Department of Oncology, University of Torino, Torino, Italy;26. Division of Hematology, Città della Salute e della Scienza Hospital, Torino, Italy;27. Division of Hematology, San Bortolo Hospital, Vicenza, Italy;28. Haemostasis Unit, Department of Clinical and Experimental Medicine, University of Catania, “Policlinico-Vittorio Emanuele” Hospital, Catania, Italy;29. Centre for Medical Education, Queenʼs University Belfast, Belfast, UK;30. Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy;31. Department of Hematology, Hospital Universitario Miguel Servet, Zaragoza, Spain;32. Center for Translational & Clinical Research Aachen (CTC-A), University Hospital RWTH Aachen, Aachen, Germany;33. Department of Medicine and Surgery, Hematology and Hematopoietic Stem Cell Transplant Center, University of Naples Federico II, Naples, Italy;34. Department of Hematology, Hospital Clínic, Barcelona, Spain;35. CRIMM-Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy

Department Experimental and Clinical Medicine, University of Florence, Firenze, Italy

Abstract:One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.
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