Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study

Tiziano Barbui; Arianna Ghirardi; Arianna Masciulli; Alessandra Carobbio; Francesca Palandri; Nicola Vianelli; Valerio De Stefano; Silvia Betti; Ambra Di Veroli; Alessandra Iurlo; Daniele Cattaneo; Federica Delaini; Massimiliano Bonifacio; Luigi Scaffidi; Andrea Patriarca; Elisa Rumi; Ilaria Carola Casetti; Clemency Stephenson; Paola Guglielmelli; Elena Maria Elli; Miroslava Palova; Laura Bertolotti; 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; Monia Marchetti; Martin Griesshammer; Alberto Alvarez-Larran; Alessandro Maria Vannucchi; Guido Finazzi

doi:10.1038/s41375-019-0487-8

Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study

Tiziano Barbui^*, Arianna Ghirardi, Arianna Masciulli, Alessandra Carobbio, Francesca Palandri, Nicola Vianelli, Valerio De Stefano, Silvia Betti, Ambra Di Veroli, Alessandra Iurlo, Daniele Cattaneo, Federica Delaini, Massimiliano Bonifacio, Luigi Scaffidi, Andrea Patriarca, Elisa Rumi, Ilaria Carola Casetti, Clemency Stephenson, Paola Guglielmelli, Elena Maria ElliMiroslava Palova, Laura Bertolotti, 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, Monia Marchetti, Martin Griesshammer, Alberto Alvarez-Larran, Alessandro Maria Vannucchi, Guido Finazzi

^*Corresponding author for this work

Internal Medicine

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Abstract

We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82–1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15–4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00–14.01), ruxolitinib (OR = 3.87, 95% CI 1.18–12.75), and for drug combination (OR = 3.47, 95% CI 1.55–7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

Original language	English
Pages (from-to)	1996-2005
Number of pages	10
Journal	Leukemia
Volume	33
Issue number	8
DOIs	https://doi.org/10.1038/s41375-019-0487-8
State	Published - 1 Aug 2019

Funding

Funders	Funder number
FROM Research Foundation
Amgen Foundation
AMGEN
Bayer
Novartis
Gilead Sciences
Celgene
Janssen Pharmaceuticals
Associazione Italiana per la Ricerca sul Cancro

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41375-019-0487-8

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Barbui, T., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., De Stefano, V., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Delaini, F., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., ... Finazzi, G. (2019). Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study. Leukemia, 33(8), 1996-2005. https://doi.org/10.1038/s41375-019-0487-8

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title = "Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study",

abstract = "We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82–1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15–4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00–14.01), ruxolitinib (OR = 3.87, 95% CI 1.18–12.75), and for drug combination (OR = 3.47, 95% CI 1.55–7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.",

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

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doi = "10.1038/s41375-019-0487-8",

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pages = "1996--2005",

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Barbui, T, Ghirardi, A, Masciulli, A, Carobbio, A, Palandri, F, Vianelli, N, De Stefano, V, Betti, S, Di Veroli, A, Iurlo, A, Cattaneo, D, Delaini, F, Bonifacio, M, Scaffidi, L, Patriarca, A, Rumi, E, Casetti, IC, Stephenson, C, Guglielmelli, P, Elli, EM, Palova, M, Bertolotti, L, Erez, D, Gomez, M, Wille, K, Perez-Encinas, M, Lunghi, F, Angona, A, Fox, ML, Beggiato, E, Benevolo, G, Carli, G, Cacciola, R, McMullin, MF, Tieghi, A, Recasens, V, Marchetti, M, Griesshammer, M, Alvarez-Larran, A, Vannucchi, AM & Finazzi, G 2019, 'Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study', Leukemia, vol. 33, no. 8, pp. 1996-2005. https://doi.org/10.1038/s41375-019-0487-8

TY - JOUR

T1 - Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study

AU - Barbui, Tiziano

AU - Ghirardi, Arianna

AU - Masciulli, Arianna

AU - Carobbio, Alessandra

AU - Palandri, Francesca

AU - Vianelli, Nicola

AU - De Stefano, Valerio

AU - Betti, Silvia

AU - Di Veroli, Ambra

AU - Iurlo, Alessandra

AU - Cattaneo, Daniele

AU - Delaini, Federica

AU - Bonifacio, Massimiliano

AU - Scaffidi, Luigi

AU - Patriarca, Andrea

AU - Rumi, Elisa

AU - Casetti, Ilaria Carola

AU - Stephenson, Clemency

AU - Guglielmelli, Paola

AU - Elli, Elena Maria

AU - Palova, Miroslava

AU - Bertolotti, Laura

AU - Erez, Daniel

AU - Gomez, Montse

AU - Wille, Kai

AU - Perez-Encinas, Manuel

AU - Lunghi, Francesca

AU - Angona, Anna

AU - Fox, Maria Laura

AU - Beggiato, Eloise

AU - Benevolo, Giulia

AU - Carli, Giuseppe

AU - Cacciola, Rossella

AU - McMullin, Mary Frances

AU - Tieghi, Alessia

AU - Recasens, Valle

AU - Marchetti, Monia

AU - Griesshammer, Martin

AU - Alvarez-Larran, Alberto

AU - Vannucchi, Alessandro Maria

AU - Finazzi, Guido

PY - 2019/8/1

Y1 - 2019/8/1

N2 - We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82–1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15–4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00–14.01), ruxolitinib (OR = 3.87, 95% CI 1.18–12.75), and for drug combination (OR = 3.47, 95% CI 1.55–7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

AB - We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82–1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15–4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00–14.01), ruxolitinib (OR = 3.87, 95% CI 1.18–12.75), and for drug combination (OR = 3.47, 95% CI 1.55–7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

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AN - SCOPUS:85066502819

SN - 0887-6924

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EP - 2005

JO - Leukemia

JF - Leukemia

IS - 8

ER -

Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study

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UN SDGs

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