Skip to main content

Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Incidence of chronic myeloid leukemia in Calgary, Alberta, Canada

BMC Research Notes volume 11, Article number: 780 (2018) Cite this article

Abstract

Objective

The epidemiology of chronic myeloid leukemia is shifting due to the aging global population and the recent discovery and availability of targeted treatment options. This study provides recent data regarding the incidence of CML in Calgary, a major Canadian city. Data from patients diagnosed with CML by bone marrow sample analysis from 2011 to 2015 were collected from the database of the sole centralized cytogenetics facility in service of Calgary and its surrounding area.

Results

With an average of 10.2 newly diagnosed cases per year in Calgary from 2011 to 2015, the incidence rate was calculated to be 0.75 cases per 100,000 person-years (95% CI 0.57–0.99). With age standardization, the incidence was 0.87 cases per 100,000 person-years (95% CI 0.82–0.91) for the Canadian population, which was low compared to other developed Western nations. The highest incidence rates were observed in the older patient categories, however there was a broad age distribution for incident cases and the median age at diagnosis was 48. There was a general male bias for CML most pronounced at the younger ages. Our description of CML incidence will help to inform healthcare planners amidst the dramatically altered treatment of this hematological neoplasm.

Introduction

Chronic myeloid leukemia (CML) is a progressive clonal myeloproliferative disorder that accounts for roughly 15% of adult leukemias [1]. Most diagnoses occur in asymptomatic patients in the chronic stage, with a small proportion of cases having progressed to the accelerated phase or blast crisis depending on the blast count [2]. CML is more predominant in males than females and it is generally described to occur later in life, however the median age of diagnosis differs between cancer registries from the late 30’s in low and middle income countries up to 65 [3, 4]. There is no strong evidence for bias towards particular ethnicities despite lower incidence rates reported in several Asian countries and populations [5, 6]. Other associated risk factors include ionizing radiation, as most famously illustrated in Japanese atomic bomb survivors [7], and recently recognized lifestyle factors including smoking and body mass [8, 9].

The pathogenesis of CML stems from a distinct chromosomal translocation, named the Philadelphia (Ph) chromosome, which fuses the bcr and abl gene sequences from chromosomes 22 and 9, respectively [10]. The expressed Bcr–Abl chimeric product is an oncoprotein with constitutive tyrosine kinase activity, leading to the proliferation of myeloid cells in the bone marrow. There are rare cases of Ph-negative or atypical CML presenting with the same histopathological clinical features as BCR–ABL1 positive CML such as an elevated granulocyte count in a CBC and high proportion of myelocytes in a peripheral blood smear [11]. Otherwise, the Ph chromosome is detected by routine karyotyping in a cytogenetics facility, with FISH or RT-PCR as supporting techniques to show evidence of the translocation. The management of CML progressed extensively after imatinib was first described in 1996 as a tyrosine kinase inhibitor (TKI) specific to BCR–ABL1 [12, 13]. Since then, second- and third-generation TKIs have been developed as alternatives for patients who have become resistant to imatinib or had poor tolerability [14]. With these highly targeted treatment options, CML survival rates have improved drastically often to give a life expectancy approaching that of the general population [15]. Concurrently, its prevalence has increased in the last decade and the requirement of continuous TKI therapy in most cases will have an impact on future healthcare spending [6].

Here, we describe the incidence of CML in Calgary, a major Canadian city, for the recent years of 2011–2015. This will add to the global literature of epidemiological data for CML and aid clinician awareness as early diagnoses in the chronic phase with low BCR–ABL1 levels and blast counts will increase the likelihood of patients’ successful response to treatment [16].

Main text

Methods

Ethics approval

This study was approved by the Health Research Ethics Board of the Alberta Cancer Committee (ID HREBA.CC-16-0830).

Data source

Patient data for this retrospective observational study were obtained from the Calgary Laboratory Services (CLS) Cancer Cytogenetics Laboratory, which receives bone marrow samples from the city of Calgary and the surrounding Southern Alberta area. In accordance with the 2008 WHO guidelines for diagnosis [17], suspected CML cases from abnormal blood counts are followed by bone marrow biopsy for chromosomal banding analysis and/or fluorescence in situ hybridization to identify the t(9;22)(q34.1;q11.2) translocation. Newly diagnosed cases within the study period of January 1, 2011 to December 31, 2015 underwent postal code verification to exclude patients living outside the City of Calgary.

Case identification

Incident cases of CML were categorized by age and gender, and incidence rates were calculated with 95% confidence intervals. Calgary population data used in the calculations were taken from Statistics Canada in the form of updated population estimates determined by post-censal coverage studies [18]. Direct age standardization of the crude CMA incidence rate to the Canadian 2011–2015 population was calculated using published methods [19] and age-categorized population estimates from Statistics Canada [20]. 95% confidence intervals were calculated for each incidence rate by Wilson score interval for binomial proportions with sample sizes of 6,775,552 and 175,645,187 representing cumulative 2011–2015 population totals for Calgary and Canada, respectively.

Results

With an average 10.2 new cases over 2011–2015, the crude incidence of CML in Calgary was 0.75 cases per 100,000 person-years (95% CI 0.57–0.99) (Table 1). With age-standardization to the Canadian population, the incidence was 0.87 cases per 100,000 person-years (95% CI 0.82–0.91). 16 cases of Ph+ CML were observed for every Ph− CML. The strong male preference (1.83:1M:F) was reflected in the age distribution of incident cases (Fig. 1), which showed a broad distribution beginning in the early teenage years and peaking in the late 70–74 and 80–84 age categories for females and males, respectively.

Table 1 Incidence features of chronic myeloid leukemia in Calgary (2011–2015)
Full size table
Fig. 1
figure1

Age- and gender-stratified incidence of chronic myeloid leukemia in Calgary from 2011 to 2015

Full size image

Discussion

Given the breakthrough developments in available therapy, ongoing refinements in diagnostic criteria and aging populations, the epidemiology of CML is radically changing [6]. Our results describing the recent incidence of CML in Calgary, a major Canadian city with a catchment population of 1.4 million, contributes to the monitoring of these shifting statistics and serves as an indication for healthcare planners in their future management of patients and resources. Obtaining accurate counts of cancer cases is a challenge that is continuously faced by registries around the world [21].

The age-standardized incidence rate of 0.87 CML cases per 100,000 person-years in Canada is considerably higher than the crude incidence calculated for Calgary, which is a reflection of the relatively younger population in the latter. These rates are low compared to other Western nations and more alarmingly, they are roughly half that of the United States (Table 2). The median age at diagnosis of 48 is also considerably lower compared to the United States and Western Europe. Instead, it is closer to the developed Asian populations of Hong Kong and Singapore. This is also likely due to the young population of Calgary, and higher incidence is still largely observed in the elderly from 65 to 84 years old (Fig. 1). Low incidence rates and ages at diagnosis are usually associated with low and middle income countries where there may be possible environmental factors and underreporting [4], however these causes are unlikely to be applicable here. The 6% incidence of atypical CML (Ph−) is higher than the generally accepted rate of 1–2% [11].

Table 2 Incidence rates per 100,000 person-years, male to female ratio, and median age of diagnosis in select global populations
Full size table

Within the 5-year study period in Calgary, there is a strong pattern of new CML diagnoses in males over females that is higher than observed in other countries. This is most pronounced at young patient ages below 45 years old where male cases outnumber female cases by 4:1. For older patients, the male-to-female ratio is reduced to 1.21:1 and in a few of these mid-to-late age categories, there are higher female incidence rates of CML than males. Hematological neoplasms are usually more common in males than females due to genetic and hormonal differences [22].

In conclusion, we report a relatively low incidence of 0.75 cases of chronic myeloid leukemia per 100,000 person-years in Calgary, Canada from 2011 to 2015 (95% CI 0.57–0.99). The median age at diagnosis is also younger compared to other developed Western nations, and a strong male bias is observed.

Limitations

The data presented here were limited by the geography and study period being considered, which skews the cohort towards a young, nonsmoking urban population. Furthermore, the summary statistics do not specify incident CML cases by phase. However, the low number of reported cases is less likely to provide accurate statistics for such classification. Future studies may also include cohort stratification by sociodemographic characteristics such as ethnicity or lifestyle factors, and consider other updated epidemiological measures such as survival rates and prevalence for CML in the TKI era.

Abbreviations

CLS:

Calgary Laboratory Services

CML:

chronic myeloid leukemia

Ph:

Philadelphia chromosome

TKI:

tyrosine kinase inhibitor

References

  1. 1.

    American Cancer Society. Cancer facts & figures 2015. Atlanta: American Cancer Society; 2015.

  2. 2.

    Cortes JE, Talpaz M, O’Brien S, Faderl S, Garcia-Manero G, Ferrajoli A, et al. Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposal. Cancer. 2006;106(6):1306–15.

  3. 3.

    Rohrbacher M, Hasford J. Epidemiology of chronic myeloid leukaemia (CML). Best Pract Res Clin Haematol. 2009;22(3):295–302.

  4. 4.

    Mendizabal AM, Garcia-Gonzalez P, Levine PH. Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries. Cancer Epidemiol. 2013;37(3):247–54.

  5. 5.

    Au WY, Caguioa PB, Chuah C, Hsu SC, Jootar S, Kim DW, et al. Chronic myeloid leukemia in Asia. Int J Hematol. 2009;89(1):14–23.

  6. 6.

    Hoglund M, Sandin F, Simonsson B. Epidemiology of chronic myeloid leukaemia: an update. Ann Hematol. 2015;94(Suppl 2):S241–7.

  7. 7.

    Hsu WL, Preston DL, Soda M, Sugiyama H, Funamoto S, Kodama K, et al. The incidence of leukemia, lymphoma and multiple myeloma among atomic bomb survivors: 1950–2001. Radiat Res. 2013;179(3):361–82.

  8. 8.

    Kabat GC, Wu JW, Moore SC, Morton LM, Park Y, Hollenbeck AR, et al. Lifestyle and dietary factors in relation to risk of chronic myeloid leukemia in the NIH-AARP Diet and Health Study. Cancer Epidemiol Biomarkers Prev. 2013;22(5):848–54.

  9. 9.

    Lauseker M, Hasford J, Saussele S, Kremers S, Kraemer D, Linemann W, et al. Smokers with chronic myeloid leukemia are at a higher risk of disease progression and premature death. Cancer. 2017;123(13):2467–71.

  10. 10.

    Leibowitz D, Young KS. The molecular biology of CML: a review. Cancer Invest. 1989;7(2):195–203.

  11. 11.

    Giri S, Pathak R, Martin MG, Bhatt VR. Characteristics and survival of BCR/ABL negative chronic myeloid leukemia: a retrospective analysis of the surveillance, epidemiology and end results database. Ther Adv Hematol. 2015;6(6):308–12.

  12. 12.

    Dudley J, Chambers T. Why the resistance to diagnostic imaging in childhood urinary tract infections. Lancet. 1996;348(9020):71–2.

  13. 13.

    Stagno G, Stella S, Spitaleri A, Pennisi MS, Di Raimondo F, Vigneri P. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes. Expert Rev Anticancer Ther. 2016;16(3):273–8.

  14. 14.

    Jabbour E, Kantarjian H, Cortes J. Use of second- and third-generation tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia: an evolving treatment paradigm. Clin Lymphoma Myeloma Leuk. 2015;15(6):323–34.

  15. 15.

    Bower H, Bjorkholm M, Dickman PW, Hoglund M, Lambert PC, Andersson TM. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851–7.

  16. 16.

    Mandal E, Bolt DM, Shah BK. Disparities in chronic myeloid leukemia survival by age, gender, and ethnicity in pre- and post-imatinib eras in the US. Acta Oncol. 2013;52(4):837–41.

  17. 17.

    Sabattini E, Bacci F, Sagramoso C, Pileri SA. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica. 2010;102(3):83–7.

  18. 18.

    Statistics Canada. Table 17-10-0078-01 Annual demographic estimates by census metropolitan area, age and sex, based on the Standard Geographical Classification (SGC). 2011. https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1710007801. Accessed 3 Oct 2018.

  19. 19.

    Boniol M, Heanue M. Age-standardisation and denominators. In: Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P, editors. Cancer incidence in five continents, IARC scientific publication no160, vol. 9. Lyon: International Agency for Research on Cancer, World Health Organization; 2008. p. 99–101.

  20. 20.

    Statistics Canada. Table 17-10-0005-01 Population estimates on July 1st, by age and sex. https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1710000501. Accessed 3 Oct 2018.

  21. 21.

    Craig BM, Rollison DE, List AF, Cogle CR. Underreporting of myeloid malignancies by United States cancer registries. Cancer Epidemiol Biomarkers Prev. 2012;21(3):474–81.

  22. 22.

    Kim HI, Lim H, Moon A. Sex differences in cancer: epidemiology, genetics and therapy. Biomol Ther (Seoul). 2018;26(4):335–42.

  23. 23.

    Chen Y, Wang H, Kantarjian H, Cortes J. Trends in chronic myeloid leukemia incidence and survival in the United States from 1975 to 2009. Leuk Lymphoma. 2013;54(7):1411–7.

  24. 24.

    Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116(19):3724–34.

  25. 25.

    Osorio S, Casado LF, Giraldo P, Maestro B, Andrade M, Redondo S, et al. Chronic myeloid leukaemia in Spain: its presentation characteristics have changed. Spanish section of the EUTOS population-based registry. Rev Clin Esp. 2016;216(6):293–300.

  26. 26.

    Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the haematological malignancy research network. Br J Cancer. 2011;105(11):1684–92.

  27. 27.

    Beinortas T, Tavoriene I, Zvirblis T, Gerbutavicius R, Jurgutis M, Griskevicius L. Chronic myeloid leukemia incidence, survival and accessibility of tyrosine kinase inhibitors: a report from population-based Lithuanian haematological disease registry 2000–2013. BMC Cancer. 2016;16:198.

  28. 28.

    Kulikov SM, Vinogradova O, Chelysheva E, Tishchenko IA, Galaiko MA, Lazareva OV, et al. [Incidence of chronic myeloid leukemia in 6 regions of Russia according to the data of the 2009–2012 population-based study]. Ter Arkh. 2014;86(7):24–30 (Russian).

  29. 29.

    Dikshit RP, Nagrani R, Yeole B, Koyande S, Banawali S. Changing trends of chronic myeloid leukemia in greater Mumbai, India over a period of 30 years. Indian J Med Paediatr Oncol. 2011;32(2):96–100.

Download references

Authors’ contributions

LN analyzed the data and wrote the manuscript draft. MG analyzed the data. CN and FRK conceived of the study, extracted the data and gave feedback on the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors thank Marcus Vaska for assistance in literature searching.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Ethics approval for this study was obtained from the Health Research Ethics Board of Alberta Cancer Committee (Ethics ID HREBA.CC-16-0830). As approved by the ethics committee, consent for participation was waived. No individual patient data were reported here.

Funding

Support for data collection and analysis was provided by a Canadian Institutes of Health Research Foundation Scheme Grant to CN [RN254781-333204].

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Author information

Affiliations

  1. Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
    • Leonard Tu Nguyen
    • , Maggie Guo
    • , Christopher Naugler
    •  & Fariborz Rashid-Kolvear
  2. Departments of Family Medicine and Community Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
    • Christopher Naugler
  3. Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
    • Fariborz Rashid-Kolvear
  4. Diagnostic and Scientific Centre, 2E-415, 9 3535 Research Road NW, Calgary, AB, T2L2K8, Canada
    • Fariborz Rashid-Kolvear
Authors
  1. Search for Leonard Tu Nguyen in:
  2. Search for Maggie Guo in:
  3. Search for Christopher Naugler in:
  4. Search for Fariborz Rashid-Kolvear in:

Corresponding author

Correspondence to Fariborz Rashid-Kolvear.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nguyen, L.T., Guo, M., Naugler, C. et al. Incidence of chronic myeloid leukemia in Calgary, Alberta, Canada. BMC Res Notes 11, 780 (2018). https://doi.org/10.1186/s13104-018-3890-8

Download citation

Keywords

  • Chronic myeloid leukemia
  • Chronic myelogenous leukemia
  • Myeloproliferative neoplasm
  • Cancer epidemiology
  • Hematological neoplasm, incidence
  • Canada

BMC Research Notes

ISSN: 1756-0500

Contact us