Lymphocyte count and risk of chronic lymphocytic leukaemia

Background Elevated absolute lymphocyte cell (ALC) count is often used as a first indication for diagnostic investigation of chronic lymphocytic leukaemia (CLL). The absolute risk of CLL as a function of age, sex and ALC has not been described. Methods We used information on pre-diagnostic ALC 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 pre-diagnostic ALC using flexible parametric survival modelling. Results Compared to research participants with ALC below 2 x109 cells/L, the risk of CLL was almost 8 times higher for those with ALC of 3 to 4x109 cells/L (HR 7.76, 95% CI: 6.24-9.65). The absolute risk of CLL was two-fold higher in males than in females. For 60-year-olds with ALC of 5x109 cells/L, 10-year CLL risk was estimated at 6.5% (95% CI: 5.6%-7.5%) for men and 3.5% (3.0%-4.1%) for women. The 10-year risk of CLL for participants with ALC of 5x109 cells/L varied between 0.91% (95% CI: 0.68-1.2%) for a 40-year-old female and 12% (95% CI: 11-15%) for a 70-year-old male. Conclusion The absolute risk of CLL is strongly influenced by age, sex and ALC. A crude ALC cut-off 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 of patients with elevated ALC.