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

Valerio De Stefano; 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 Imogen Methven Stephenson; Paola Guglielmelli; Elena Maria Elli; Miroslava Palova; Davide Rapezzi; Daniel Erez; Montse Gomez; Kai Wille; Manuel Perez-Encinas; Francesca Lunghi; Anna Angona; María-Laura Fox; Eloise Beggiato; Giulia Benevolo; Giuseppe Carli; Rossella Cacciola; Mary Frances McMullin; Alessia Tieghi; Valle Recasens; Susanne Isfort; Monia Marchetti; Martin Griesshammer; Alberto Alvarez-Larran; Alessandro Maria Vannucchi; Alessandro Rambaldi; Tiziano Barbui

doi:10.1182/blood.2019002614

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

Valerio De Stefano, 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 Imogen Methven Stephenson, Paola Guglielmelli, Elena Maria ElliMiroslava Palova, Davide Rapezzi, Daniel Erez, Montse Gomez, Kai Wille, Manuel Perez-Encinas, Francesca Lunghi, Anna Angona, María-Laura Fox, Eloise Beggiato, Giulia Benevolo, Giuseppe Carli, Rossella Cacciola, Mary Frances McMullin, Alessia Tieghi, Valle Recasens, Susanne Isfort, Monia Marchetti, Martin Griesshammer, Alberto Alvarez-Larran, Alessandro Maria Vannucchi, Alessandro Rambaldi, Tiziano Barbui

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Abstract

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.

Original language	English
Journal	Blood
Early online date	23 Dec 2019
DOIs	https://doi.org/10.1182/blood.2019002614
Publication status	Early online date - 23 Dec 2019

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Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer. A case-control study
Copyright 2019 American Society of Hematology. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 1.04 MBLicence: Unspecified

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De Stefano, V., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Rossi, E., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C. I. M., Guglielmelli, P., ... Barbui, T. (2019). Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer. A case-control study. Blood. Advance online publication. https://doi.org/10.1182/blood.2019002614

@article{7b378c0776c44565ac9349946de44d19,

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

abstract = "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.",

author = "{De Stefano}, Valerio and Arianna Ghirardi and Arianna Masciulli and Alessandra Carobbio and Francesca Palandri and Nicola Vianelli and Elena Rossi and Silvia Betti and {Di Veroli}, Ambra and Alessandra Iurlo and Daniele Cattaneo and Guido Finazzi and Massimiliano Bonifacio and Luigi Scaffidi and Andrea Patriarca and Elisa Rumi and Casetti, {Ilaria Carola} and Stephenson, {Clemency Imogen Methven} and Paola Guglielmelli and Elli, {Elena Maria} and Miroslava Palova and Davide Rapezzi and Daniel Erez and Montse Gomez and Kai Wille and Manuel Perez-Encinas and Francesca Lunghi and Anna Angona and Mar{\'i}a-Laura Fox and Eloise Beggiato and Giulia Benevolo and Giuseppe Carli and Rossella Cacciola and McMullin, {Mary Frances} and Alessia Tieghi and Valle Recasens and Susanne Isfort and Monia Marchetti and Martin Griesshammer and Alberto Alvarez-Larran and Vannucchi, {Alessandro Maria} and Alessandro Rambaldi and Tiziano Barbui",

note = "Copyright {\textcopyright} 2019 American Society of Hematology.",

year = "2019",

month = dec,

day = "23",

doi = "10.1182/blood.2019002614",

language = "English",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier B.V.",

}

De Stefano, V, Ghirardi, A, Masciulli, A, Carobbio, A, Palandri, F, Vianelli, N, Rossi, E, Betti, S, Di Veroli, A, Iurlo, A, Cattaneo, D, Finazzi, G, Bonifacio, M, Scaffidi, L, Patriarca, A, Rumi, E, Casetti, IC, Stephenson, CIM, Guglielmelli, P, Elli, EM, Palova, M, Rapezzi, D, Erez, D, Gomez, M, Wille, K, Perez-Encinas, M, Lunghi, F, Angona, A, Fox, M-L, Beggiato, E, Benevolo, G, Carli, G, Cacciola, R, McMullin, MF, Tieghi, A, Recasens, V, Isfort, S, Marchetti, M, Griesshammer, M, Alvarez-Larran, A, Vannucchi, AM, Rambaldi, A & Barbui, T 2019, 'Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer. A case-control study', Blood. https://doi.org/10.1182/blood.2019002614

TY - JOUR

T1 - Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer. A case-control study

AU - De Stefano, Valerio

AU - Ghirardi, Arianna

AU - Masciulli, Arianna

AU - Carobbio, Alessandra

AU - Palandri, Francesca

AU - Vianelli, Nicola

AU - Rossi, Elena

AU - Betti, Silvia

AU - Di Veroli, Ambra

AU - Iurlo, Alessandra

AU - Cattaneo, Daniele

AU - Finazzi, Guido

AU - Bonifacio, Massimiliano

AU - Scaffidi, Luigi

AU - Patriarca, Andrea

AU - Rumi, Elisa

AU - Casetti, Ilaria Carola

AU - Stephenson, Clemency Imogen Methven

AU - Guglielmelli, Paola

AU - Elli, Elena Maria

AU - Palova, Miroslava

AU - Rapezzi, Davide

AU - Erez, Daniel

AU - Gomez, Montse

AU - Wille, Kai

AU - Perez-Encinas, Manuel

AU - Lunghi, Francesca

AU - Angona, Anna

AU - Fox, María-Laura

AU - Beggiato, Eloise

AU - Benevolo, Giulia

AU - Carli, Giuseppe

AU - Cacciola, Rossella

AU - McMullin, Mary Frances

AU - Tieghi, Alessia

AU - Recasens, Valle

AU - Isfort, Susanne

AU - Marchetti, Monia

AU - Griesshammer, Martin

AU - Alvarez-Larran, Alberto

AU - Vannucchi, Alessandro Maria

AU - Rambaldi, Alessandro

AU - Barbui, Tiziano

PY - 2019/12/23

Y1 - 2019/12/23

N2 - 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.

AB - 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.

U2 - 10.1182/blood.2019002614

DO - 10.1182/blood.2019002614

M3 - Article

C2 - 31869407

SN - 0006-4971

JO - Blood

JF - Blood

ER -

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

Abstract

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