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Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Sundsvall Research Unit, Umeå University)
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
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2016 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 7, p. 1562-1567Article in journal (Refereed) Published
Abstract [en]

We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

Place, publisher, year, edition, pages
2016. Vol. 30, no 7, p. 1562-1567
National Category
Hematology
Identifiers
URN: urn:nbn:se:umu:diva-127522DOI: 10.1038/leu.2016.59ISI: 000379504400013PubMedID: 27080811OAI: oai:DiVA.org:umu-127522DiVA, id: diva2:1046710
Available from: 2016-11-15 Created: 2016-11-15 Last updated: 2018-06-09Bibliographically approved
In thesis
1. Chronic myeloid leukemia and cancer
Open this publication in new window or tab >>Chronic myeloid leukemia and cancer
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

Chronic myeloid leukemia (CML) is a relatively rare hematological malignancy with a constant incidence of approximately 90 new cases each year in Sweden (0.9 cases/100 000 inhabitants). The etiology is largely unknown but high doses of ionizing radiation are a known but rare risk factor. The treatment options were for a long time limited to chemotherapies i.e. hydroxyurea and busulfan, interferon’s and allogeneic hematopoietic stem cell transplantation and the median survival were only about four years.

Since the beginning of the 21st century a new way of treating CML has been introduced, the tyrosine kinase inhibitors (TKI), leading to a rapid decrease in leukemic cells and symptoms. Due to the TKIs, the overall 5-year survival is nowadays approximately 85 % and CML patients have time to develop other diseases, including other malignancies.

The aims of this thesis was to investigate the present and future prevalence of CML and the prevalence of other malignancies prior and subsequent to the diagnosis of CML, malignancies among first-degree relatives of persons with CML. In addition, the incidence of autoimmune and chronic inflammatory diseases among patients with CML was also investigated.

 

Methods

From the Swedish CML register, data over nearly all Swedish CML patients from 2002 and forward were obtained for paper II-IV.

For paper I, the Swedish cancer register was used to identify all Swedish CML patients since 1970 and the Swedish cause of death register was used to identify an eventual date of death for these patients. With a constant incidence and the relative survival rates for CML patients between 2006 and 2012 as a model, the present and future prevalence was calculated.

For paper II-IV, data from the Swedish cancer register was used to identify other malignancies than CML. For paper II, information about autoimmune and chronic inflammatory diseases was retrieved from the Swedish national patient register.

For paper II and IV, five controls matched for year of birth, gender and county of residence were randomly selected from the Swedish register of the total population. To calculate odds ratio (OR), conditional logistic regression was used.

To calculate the risk of a second malignancy for paper III, Standardized incidence ratio (SIR) was used.

In paper IV, first-degree relatives (parents, siblings and offsprings) for both cases and controls were retrieved from the Swedish multi-Generation Register, where persons born later than 1932 and registered in Sweden at some time since 1961 are registered.

 

Results

Prevalence and survival

As shown in paper I, the 5-year overall survival for CML patients increased remarkably from 0.18 to 0.82 between 1970 and 2012. The prevalence increased from 3.9 to 11.9 per 100 000 inhabitants in Sweden between 1985 and 2012. By assuming no further improvements in relative survival as compared to the survival rates between 2006 and 2012, the prevalence by 2060 is expected to increase to 22.0 per 100 000 inhabitants. This corresponds to 2 587 CML patients as compared to 1 137 CML patients in 2012.

 

Malignancies, autoimmune and chronic inflammatory diseases prior to CML

In study II, more than 45 000 person-years of follow-up were evaluated in 984 CML patients diagnosed between 2002 and 2012. With an OR of 1.47 (95 % CI 1.20–1.82) and 1.55 (95 % CI 1.21–1.98), respectively, the prevalence of prior malignancies and autoimmune diseases were significantly increased as compared to matched controls. On the other hand, no association between CML and chronic inflammatory diseases was shown.

 

Second malignancies

In 868 CML patients, diagnosed between 2002 and 2011, 52 malignancies were observed in the Swedish cancer register, as shown in paper III. When compared to expected rates in the background population, a significantly increased risk of second malignancies with a SIR of 1.52 (95 % CI 1.13–1.99) was shown. When looking at specific cancer types, gastrointestinal as well as nose and throat cancer were significantly increased.

 

Familial aggregation of malignancies

984 CML patients were identified in paper IV. However, 184 had a birth date prior to 1932, subsequently only 800 patients were analyzed. Among them, 4 287 first-degree relatives were identified, compared to 20 930 first-degree relatives of the matched controls. 611 malignancies were retrieved; no significant increase of malignancies in first-degree relatives of CML patients was shown (OR 1.06; 95 % CI: 0.96–1.16).

 

Conclusion

Since CML patients nowadays have a high survival rate, the calculations in this thesis shows that the prevalence of CML will almost double by 2060. CML patients have an increased risk of developing malignancies prior and subsequent to the diagnosis of CML, suggesting a hereditary or acquired predisposition to develop cancer. Since there is no familial aggregation of malignancies in CML patients, a hereditary predisposition to develop cancer is unlikely to be part of the pathogenesis of CML, leaving an acquired predisposition more likely.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2017. p. 70
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1925
Keywords
Chronic myeloid leukemia, Prevalence, Malignancies, Odds ratio, Standardized Incidence Ratio, Outcome, Autoimmune diseases, Survival
National Category
Hematology Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology; Medicine
Identifiers
urn:nbn:se:umu:diva-141144 (URN)978-91-7601-781-4 (ISBN)
Public defence
2017-11-24, Hörsal D, Unod T9, 9 tr, Norrlands Universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-11-02 Created: 2017-10-26 Last updated: 2018-06-09Bibliographically approved

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Gunnarsson, NiklasWållberg-Jonsson, SolveigSjälander, Anders

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