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.

Center for Translational and Clinical Research Aachen University Hospital RWTH Aachen Aachen Germany

Centre for Medical Education Queen's University Belfast Belfast UK

CRIMM Center of Research and Innovation of Myeloproliferative Neoplasms Azienda Ospedaliera Universitaria Careggi Firenze Italy

Deparment of Hematology Hospital Clínico Universitario de Santiago de Compostela Santiago de Compostela Spain

Department Experimental and Clinical Medicine University of Florence Firenze Italy

Department of Hemato oncology University Hospital Olomouc Olomouc Czech Republic

Department of Hematology Hospital Clínic Barcelona Spain

Department of Hematology Hospital Clínico Universitario Valencia Spain

Department of Hematology Hospital del Mar Barcelona Spain

Department of Hematology Hospital Universitario Miguel Servet Zaragoza Spain

Department of Hematology Hospital Universitario Vall d'Hebron Barcelona Spain

Department of Hematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Pavia Italy

Department of Medicine and Surgery Hematology and Hematopoietic Stem Cell Transplant Center University of Naples Federico 2 Naples Italy

Department of Medicine Section of Hematology University of Verona Verona Italy

Department of Molecular Medicine University of Pavia Pavia Italy

Division of Hematology Città della Salute e della Scienza Hospital Torino Italy

Division of Hematology Department of Translational Medicine University of Eastern Piedmont Novara Italy

Division of Hematology Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan Milan Italy

Division of Hematology Ospedale San Gerardo ASST Monza Italy

Division of Hematology Papa Giovanni XXIII Hospital Bergamo Italy

Division of Hematology San Bortolo Hospital Vicenza Italy

Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

FROM Research Foundation Papa Giovanni XXIII Hospital Bergamo Italy

Guy's and St Thomas' NHS Foundation Trust London UK

Haemostasis Unit Department of Clinical and Experimental Medicine University of Catania Policlinico Vittorio Emanuele Hospital Catania Italy

Hematology and Bone Marrow Transplantation Unit IRCCS San Raffaele Scientific Institute Milan Italy

Hematology Institute and Blood Bank Meir Medical Center Kfar Saba Israel

Hematology Unit Azienda Unità Sanitaria Locale IRCCS di Reggio Emilia Reggio Emilia Italy

Institute of Hematology Catholic University Rome Italy

Institute of Hematology L and A Seràgnoli S Orsola Malpighi Hospital Bologna Italy

Oncology Unit Cardinal Massaia Hospital Asti Italy

Rete Laziale MPN Rome Italy

S C Ematologia Azienda Ospedaliera S Croce e Carle Cuneo Italy

Sackler School of Medicine Tel Aviv University Tel Aviv Israel

Unit of Hematology Department of Oncology University of Torino Torino Italy

University Clinic for Hematology and Oncology Minden University of Bochum Minden Germany

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