Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer. A case-control study

Patients with Philadelphia-negative myeloproliferative neoplasms (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma (n=426), non-melanoma skin cancer (n=127), hematological second cancer (n=62) and melanoma (n=32) diagnosed concurrently or after the diagnosis of MPN. Up to 3 controls (n=1,234) without history of cancer matched with each case for center, sex, age at MPN diagnosis, date of diagnosis and MPN disease duration were included. Cases were comparable to controls for MPN type, exposure to driver mutations, and cardiovascular risk factors. The frequency of thrombosis preceding MPN diagnosis was similar for cases (19.8%) and controls (21.2%) (p=0.462). Thrombotic events recorded after MPN diagnosis and before second cancer were higher in cases than in controls (75/647, 11.6%, vs. 100/1234. 8.1%, p=0.013), because of a higher proportion of arterial thromboses (40/647, 6.2% vs. 46/1234, 3.7%, p=0.015). After adjusting for many confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio 1.97, 95% CI 1.14-3.41, p=0.015), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance to detect early carcinoma.