Skip to main content
Top
Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

Association between multiple sclerosis, cancer risk, and immunosuppressant treatment: a cohort study

Authors: Paolo Ragonese, Paolo Aridon, Giulia Vazzoler, Maria Antonietta Mazzola, Vincenzina Lo Re, Marianna Lo Re, Sabrina Realmuto, Simona Alessi, Marco D’Amelio, Giovanni Savettieri, Giuseppe Salemi

Published in: BMC Neurology | Issue 1/2017

Login to get access

Abstract

Background

The association between multiple sclerosis (MS) and cancer has long been investigated with conflicting results. Several reports suggest an increased cancer risk among MS patients treated with immunosuppressant (IS) drugs.

Methods

We performed a cohort study including MS patients recruited at the Neurological Department of the University of Palermo. Mean follow-up period was ten years for the whole cohort. We calculated cancer incidence among patients treated with IS. Incidence rates were compared in the cohort by calculating the relative risk according to length and dose of exposure to IS. Cancer incidence among MS patients was compared to cancer incidence in the general population of Sicily in similar age groups.

Results

On an overall cohort of 531 MS patients (346 women and 185 men) exposed to IS, we estimated a crude incidence rate for cancer of 2.26% (2.02% in women, 2.7% in men). Cancer risk was higher compared to rates observed among an equal number of patients not exposed to IS, and to the risk in the general population in Sicily at similar age groups (adjusted HR: 11.05; CI 1.67–73.3; p = 0.013).

Conclusion

The present study showed a higher cancer risk in MS patients associated only to previous IS exposure. Studies on long-term outcomes are essential to evaluate the possibility that treatment options that need to be considered for a long time-period may modify risk for life threatening diseases.
Literature
1.
go back to reference Compston ACC, Lassmann H, McDonald I, Miller D, Noseworthy J, Smith K, et al. McAlpine’s Multiple Sclerosis. fourth ed. Philadelphia: Churchill Livingstone Elsevier; 2004. Compston ACC, Lassmann H, McDonald I, Miller D, Noseworthy J, Smith K, et al. McAlpine’s Multiple Sclerosis. fourth ed. Philadelphia: Churchill Livingstone Elsevier; 2004.
2.
go back to reference Wingerchuk DM, Carter JL. Multiple Sclerosis: Current and Emerging Disease-Modifying Therapies and Treatment Strategies. Mayo Clinic Procedings. 2014;89:225–40.CrossRef Wingerchuk DM, Carter JL. Multiple Sclerosis: Current and Emerging Disease-Modifying Therapies and Treatment Strategies. Mayo Clinic Procedings. 2014;89:225–40.CrossRef
3.
go back to reference Casetta I, Iuliano G, Filippini G. Azathioprine for multiple sclerosis. Cochrane Database Syst Rev. 2007;4:CD003982. Casetta I, Iuliano G, Filippini G. Azathioprine for multiple sclerosis. Cochrane Database Syst Rev. 2007;4:CD003982.
4.
go back to reference Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G. Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev. 2013;4:CD002127. Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G. Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev. 2013;4:CD002127.
5.
go back to reference The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet. 1991;337:441–6. The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet. 1991;337:441–6.
6.
go back to reference Hauser SL, Dawson DM, Lehrich JR, Lerich JL, Beal MF, Kevy SV, Propper RD, Mills JA, Weiner HL. Intensive immunosuppression in progressive multiple sclerosis: a randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med. 1983;308:173–80.CrossRefPubMed Hauser SL, Dawson DM, Lehrich JR, Lerich JL, Beal MF, Kevy SV, Propper RD, Mills JA, Weiner HL. Intensive immunosuppression in progressive multiple sclerosis: a randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med. 1983;308:173–80.CrossRefPubMed
7.
go back to reference Marriott JJ, Miyasaki JM, Gronseth G, O'Connor PW. Evidence report: the efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1463–70.CrossRefPubMedPubMedCentral Marriott JJ, Miyasaki JM, Gronseth G, O'Connor PW. Evidence report: the efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1463–70.CrossRefPubMedPubMedCentral
8.
go back to reference Bahmanyar S, Montgomery SM, Hillert J, Ekbom A, Olsson T. Cancer risk among patients with multiple sclerosis and their parents. Neurology. 2009;72:1170–7.CrossRefPubMed Bahmanyar S, Montgomery SM, Hillert J, Ekbom A, Olsson T. Cancer risk among patients with multiple sclerosis and their parents. Neurology. 2009;72:1170–7.CrossRefPubMed
9.
go back to reference Kingwell E, Bajdik C, Phillips N, Zhu F, Oger J, Hashimoto S, Tremlett H. Cancer risk in multiple sclerosis: findings from British Columbia, Canada. Brain. 2012;135:2973–9.CrossRefPubMed Kingwell E, Bajdik C, Phillips N, Zhu F, Oger J, Hashimoto S, Tremlett H. Cancer risk in multiple sclerosis: findings from British Columbia, Canada. Brain. 2012;135:2973–9.CrossRefPubMed
10.
go back to reference Martinelli V, Cocco E, Capra R, Salemi G, Gallo P, Capobianco M, Pesci I, Ghezzi A, Pozzilli C, Lugaresi A, Bellantonio P, Amato MP, Grimaldi LM, Trojano M, Mancardi GL, Bergamaschi R, Gasperini C, Rodegher M, Straffi L, Ponzio M, Comi G. Italian Mitoxantrone Group. Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone. Neurology. 2011;77:1887–95.CrossRefPubMed Martinelli V, Cocco E, Capra R, Salemi G, Gallo P, Capobianco M, Pesci I, Ghezzi A, Pozzilli C, Lugaresi A, Bellantonio P, Amato MP, Grimaldi LM, Trojano M, Mancardi GL, Bergamaschi R, Gasperini C, Rodegher M, Straffi L, Ponzio M, Comi G. Italian Mitoxantrone Group. Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone. Neurology. 2011;77:1887–95.CrossRefPubMed
11.
go back to reference Stroet A, Hemmelmann C, Starck M, Zettl U, Dörr J, Friedemann P, Flachenecker P, Fleischer V, Zipp F, Nückel H, Kieseier BC, Ziegler A, Gold R, Chan A. Incidence of therapy-related acute leukaemia in mitoxantrone-treated multiple sclerosis patients in Germany. Ther Adv Neurol Disord. 2012;5:75–9.CrossRefPubMedPubMedCentral Stroet A, Hemmelmann C, Starck M, Zettl U, Dörr J, Friedemann P, Flachenecker P, Fleischer V, Zipp F, Nückel H, Kieseier BC, Ziegler A, Gold R, Chan A. Incidence of therapy-related acute leukaemia in mitoxantrone-treated multiple sclerosis patients in Germany. Ther Adv Neurol Disord. 2012;5:75–9.CrossRefPubMedPubMedCentral
13.
go back to reference Nielsen NM, Rostgaard K, Rasmussen S, Koch-Henriksen N, Storm HH, Melbye M, Hjalgrim H. Cancer risk among patients with multiple sclerosis: a population-based register study. Int J Cancer. 2006;118:979–84.CrossRefPubMed Nielsen NM, Rostgaard K, Rasmussen S, Koch-Henriksen N, Storm HH, Melbye M, Hjalgrim H. Cancer risk among patients with multiple sclerosis: a population-based register study. Int J Cancer. 2006;118:979–84.CrossRefPubMed
14.
go back to reference Landgren AM, Landgren O, Gridley G, Dores GM, Linet MS, Morton LM. Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans. Cancer. 2011;117:1163–71.CrossRefPubMed Landgren AM, Landgren O, Gridley G, Dores GM, Linet MS, Morton LM. Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans. Cancer. 2011;117:1163–71.CrossRefPubMed
15.
go back to reference Le Bouc R, Zéphir H, Majed B, Vérier A, Marcel M, Vermersch P. No increase in cancer incidence detected after cyclophosphamide in a French cohort of patients with progressive multiple sclerosis. Mult Scler. 2012;18:55–63.CrossRefPubMed Le Bouc R, Zéphir H, Majed B, Vérier A, Marcel M, Vermersch P. No increase in cancer incidence detected after cyclophosphamide in a French cohort of patients with progressive multiple sclerosis. Mult Scler. 2012;18:55–63.CrossRefPubMed
17.
go back to reference Achiron A, Barak Y, Gail M, Mandel M, Pee D, Ayyagari R, Rotstein Z. Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments. Breast Cancer Res Treat. 2005;89:265–70.CrossRefPubMed Achiron A, Barak Y, Gail M, Mandel M, Pee D, Ayyagari R, Rotstein Z. Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments. Breast Cancer Res Treat. 2005;89:265–70.CrossRefPubMed
18.
go back to reference Lalmohamed A, Bazelier MT, Van Staa TP, Uitdehaag BM, Leufkens HG, De Boer A, De Vries F. Causes of death in patients with multiple sclerosis and matched referent subjects: a population-based cohort study. Eur J Neurol. 2012;19:1007–14.CrossRefPubMed Lalmohamed A, Bazelier MT, Van Staa TP, Uitdehaag BM, Leufkens HG, De Boer A, De Vries F. Causes of death in patients with multiple sclerosis and matched referent subjects: a population-based cohort study. Eur J Neurol. 2012;19:1007–14.CrossRefPubMed
19.
go back to reference Marcus A, Gowen BG, Thompson TW, Iannello A, Ardolino M, Deng W, Wang L, Shifrin N, Raulet DH. Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol. 2014;122:91–128.CrossRefPubMedPubMedCentral Marcus A, Gowen BG, Thompson TW, Iannello A, Ardolino M, Deng W, Wang L, Shifrin N, Raulet DH. Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol. 2014;122:91–128.CrossRefPubMedPubMedCentral
20.
go back to reference Gale RP, Opelz G. Commentary: does immune suppression increase risk of developing acute myeloid leukemia? Leukemia. 2012;26:422–3.CrossRefPubMed Gale RP, Opelz G. Commentary: does immune suppression increase risk of developing acute myeloid leukemia? Leukemia. 2012;26:422–3.CrossRefPubMed
21.
go back to reference Marrie RA, Cohen J, Stuve O, Trojano M, Sørensen PS, Reingold S, Cutter G, Reider N. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: Overview. Mult Scler J. 2015;3:294–304.CrossRef Marrie RA, Cohen J, Stuve O, Trojano M, Sørensen PS, Reingold S, Cutter G, Reider N. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: Overview. Mult Scler J. 2015;3:294–304.CrossRef
22.
go back to reference Kingwell E, Evans C, Zhu F, Oger J, Hashimoto S, Tremlett H. Assessment of cancer risk with β-interferon treatment for multiple sclerosis. J Neurol Neurosurg Psychiatr. 2014;85:1096–102.CrossRefPubMed Kingwell E, Evans C, Zhu F, Oger J, Hashimoto S, Tremlett H. Assessment of cancer risk with β-interferon treatment for multiple sclerosis. J Neurol Neurosurg Psychiatr. 2014;85:1096–102.CrossRefPubMed
Metadata
Title
Association between multiple sclerosis, cancer risk, and immunosuppressant treatment: a cohort study
Authors
Paolo Ragonese
Paolo Aridon
Giulia Vazzoler
Maria Antonietta Mazzola
Vincenzina Lo Re
Marianna Lo Re
Sabrina Realmuto
Simona Alessi
Marco D’Amelio
Giovanni Savettieri
Giuseppe Salemi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0932-0

Other articles of this Issue 1/2017

BMC Neurology 1/2017 Go to the issue