Lymphocyte count and risk of chronic lymphocytic leukemia

Elevated absolute lymphocyte count is often used as a first indication for diagnostic investigation of chronic lymphocytic leukemia (CLL). The absolute risk of CLL as a function of age, sex, and absolute lymphocyte count has not been described.

We used information about prediagnostic absolute lymphocyte cell count on 475 399 longitudinally followed research participants from UK Biobank, with a median follow-up of 11.6 years, during which 854 participants were diagnosed with CLL. A CLL risk model was developed based on sex, age at recruitment, and prediagnostic absolute lymphocyte count using flexible parametric survival modelling.

Compared with research participants who had absolute lymphocyte counts below 2 × 109/L, the risk of CLL was almost 8 times higher for individuals with absolute lymphocyte counts of 3 to 4 × 109/L (hazard ratio = 7.76, 95% CI = 6.24 to 9.65). The absolute risk of CLL was 2-fold higher in male than in female individuals. For 60-year-old persons with absolute lymphocyte counts of 5 ×109/L, 10-year CLL risk was estimated at 6.5% (95% CI = 5.6% to 7.5%) for men and 3.5% (95% CI = 3.0% to 4.1%) for women. The 10-year risk of CLL for participants with absolute lymphocyte counts of 5 ×109/L varied between 0.91% (95% CI = 0.68% to 1.2%) for a 40-year-old woman and 12% (95% CI = 11% to 15%) for a 70-year-old man.

The absolute risk of CLL is strongly influenced by age, sex, and absolute lymphocyte count. A crude absolute lymphocyte count cutoff to indicate further investigation for CLL without taking age and sex into consideration will identify some individuals who are at low risk. These results may be considered when establishing guidelines for clinical management in patients with elevated absolute lymphocyte counts.