Epidemiology

Epidemiology

  • It is estimated that there were approximately 21,000 new cases of chronic lymphocytic leukemia (CLL) in the United States in 2018. CLL cases make up 1.2% of all new cancer cases in the US.1
  • Approximately 4,500 individuals died in 2018 from CLL. CLL-related deaths account for 0.7% of all cancer deaths in the US.1
  • CLL accounts for approximately one-quarter of all new leukemia cases. It is the most common leukemia in adults in western countries.2
  • The percentage of individuals who survive 5 years or more after being diagnosed with CLL is 84.2%.1
  • CLL is most frequently diagnosed in people between the ages of 65 and 74, with a median age at diagnosis of 70 years.1
  • The median age at death is 80 years for CLL patients, with the highest rate of death among patients older than 85 years.1
  • With the exception of patients aged 75 or older with Rai stage 0 disease, all CLL patients have a reduced life expectancy relative to age-matched controls.3
  • Over the last 10 years, the rates for new CLL cases have been falling on average 1.0% each year and death rates have been declining by 2.8% on average each year.1
  • CLL is more common in males, with 12,990 estimate new cases in males each year and 7,950 new cases in females.4
  • The incidence of CLL is highest among Caucasians, intermediate among Africans and African-Americans, and low among Asians and Pacific Islanders.5,6
  • African-American patients are diagnosed with CLL at a younger age than white Americans (67 vs 70 years) and have poorer survival rates (63.9% vs 77.1%).5,7
  • A study of cancer development in patients who survived >10 years with CLL found that 36% of these long-term survivors will develop a second primary cancer. The most common cancers were non-melanoma skin cancer, prostate cancer, breast cancer, melanoma, lung cancer, [other] leukemia[s], and gastrointestinal tumors. The rate of cancer development was similar between patients who received treatment for CLL and those who were untreated.8

Risk Factors

  • Age: older individuals are at a greater risk of developing CLL. Approximately 90% of CLL patients are over the age of 50.9,10
  • Gender: Males are more likely to develop CLL than females.9,10
  • Race: CLL is more common in white individuals in Europe and North America. Asians in North America and Asia have a low risk of developing CLL.9,10
  • Certain chemical exposures: some studies have linked a higher risk of CLL to exposure to Agent Orange, certain pesticides, and radon.9,10
  • Family history: individuals with first-degree family members (parents, siblings, children) with CLL have twice the risk of developing this cancer.9,10
  • Monoclonal B-cell lymphocytosis: This condition occurs when an individual has a higher than normal number of lymphocytes. There is a slight risk that these cells can develop into CLL.9
  • There are five independent prognostic factors that predict the aggressiveness of CLL:11
    • TP53 status (no abnormalities vs. del(17p) or TP53 mutation or both): a mutation in TP53 is associated with a poorer prognosis. The 30-month estimated progression-free survival for patients with del(17p) is 48% compared to 87% for patients without the deletion.12
    • Mutational status of the variable portion of the immunoglobulin gene (IGHV) (mutated vs unmutated): an unmutated IGHV gene is associated with a poorer prognosis.
    • Serum β2-microglobulin concentration (β2-m) (<5 mg/L vs. >3.5 mg/L): β2-m is constantly released by lymphocytes and serum levels of this protein increase with increasing tumor burdens. 
      Higher β2-m levels are associated with a poorer prognosis.13
    • Clinical stage (Binet A or Rai 0 vs Binet B to C or Rai I to IV): a higher stage is associated with a poorer prognosis.
    • Age (<65 years vs >65 years): older individuals have a poorer prognosis than younger patients.

References

  1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER). https://seer.cancer.gov/statfacts/html/clyl.html. Accessed March 19, 2019.
  2. American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/key-statistics.html. Accessed March 19, 2019.
  3. Shanafelt TD, Rabe KG, Kay NE, et al. Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia. Cancer. 2010;116:4777-4787.
  4. Siegel RL, Miller KD, Jemal A. Cancer statistics. 2018. CA Cancer J Clin. 2018;68(1):7-30.
  5. Shenoy PJ, Malik N, Sinha R, et al. Racial differences in the presentation and outcomes of chronic lymphocytic leukemia and variants in the United States. Clin Lymphoma Myeloma Leuk. 2011;11:498-506.
  6. Lenartova A, Johannesen TB, Tjønnfjord GE. National trends in incidence and survival of chronic lymphocytic leukemia in Norway for 1953–2012: a systematic analysis of population‐based data. Cancer Med. 2016;5(12):3588-3595.
  7. Falchi L, Keating MJ, Wang X. Clinical characteristics, response to therapy, and survival of African American patients diagnosed with chronic lymphocytic leukemia: joint experience of the MD Anderson Cancer Center and Duke University Medical Center. Cancer. 2013;119(17):3177–3185.
  8. Falchi L, Vitale C, Keating MJ, et al. Incidence and prognostic impact of other cancers in a population of long-term survivors of chronic lymphocytic leukemia. Ann Oncol. 2016;27(6):1100-1106.
  9. Cancer.net Leukemia – Chronic Lymphocytic – CLL: Risk Factors. https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/risk-factors. Accessed March 19, 2019.
  10. American Cancer Society. What are the Risk Factors for Chronic Lymphocytic Leukemia? https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/causes-risks-prevention/risk-factors.html. Accessed March 19, 2019.
  11. International CLL-IPI Working Group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17:779- 790.
  12. Jones JA, Mato AR, Wierda WG, et al. Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicenter, open-label, phase 2 trial. Lancet. 2018;19(1):65-75.
  13. Gentile M, Cutrona G, Neri A, et al. Predictive value of β2-microglobulin (β2-m) levels in chronic lymphocytic leukemia since Binet A stages. Haematologica. 2009;94(6):887-888.