Chronic lymphocytic leukemia in young (≤ 55 years) patients: a comprehensive analysis of prognostic factors and outcomes

Abstract

The clinical characteristics and outcomes of younger (≤ 55 years) patients with chronic lymphocytic leukemia in the era of modern prognostic biomarkers and chemoimmunotherapy are not well understood. Baseline characteristics and outcomes of patients with chronic lymphocytic leukemia ≤ 55 years who were seen at the Mayo Clinic between January 1995 and April 2012 were compared with those of patients >55 years. The overall survival of patients ≤ 55 years was compared to that of the age- and sex-matched normal population. The characteristics of 844 newly diagnosed chronic lymphocytic leukemia patients ≤ 55 years old (median, 50 years) were compared to those of 2324 patients >55 years old (median, 67 years). Younger patients were more likely to have Rai stage I or II disease (P<0.0001), be IGHV unmutated (P=0.002) and express ZAP-70 (P=0.009). These differences became more pronounced when the ≤ 55 age group was sub-stratified into age ≤ 45, 46-50 and 51-55 years. After a median follow-up of 5.5 years, 426 (51%) patients ≤ 55 years old had received treatment, and 192 (23%) had died. The time to treatment was shorter in patients ≤ 55 years than in those older than 55 years (4.0 years versus 5.2 years; P=0.001) and those ≤ 55 years had longer survival (12.5 years versus 9.5 years; P<0.0001). However, patients ≤ 55 years had significantly shorter survival than the age- and sex-matched normal population (12.5 years versus not reached; P<0.0001). Our study is the first comprehensive analysis of younger patients with chronic lymphocytic leukemia in the modern era. Adverse prognostic markers appear more common among young patients. Although the survival of young chronic lymphocytic leukemia patients is longer than that of those >55 years old, their survival relative to the age- and sex-matched normal population is profoundly shortened.

Figure 1.

(A) Time to first treatment in patients ≤ 55 years vs. >55 years. (B) Overall survival of patients ≤ 55 years vs. >55 years

Figure 2.

(A) Time to first treatment in ≤ 45 vs. 46–50 vs. 51–55 years the age groups. (B) Overall survival in the age groups ≤ 45 vs. 46–50 vs. 51–55 years.

Figure 3.

(A) Overall survival of young (≤55 years) CLL patients relative to that of the age- and sex-matched normal population. (B) Overall survival of young (≤55 years) CLL patients with Rai stage 0 and mutated IGHV gene (red solid line) compared to that of the age-and sex-matched normal population (black dashed line). (C) Overall survival of young (≤55 years) CLL patients with Rai stage 0 and favorable-risk FISH category (normal or 13q-, red solid line) compared to an age-and sex-matched normal population (black dashed line). (D) Overall survival of young (≤55 years) CLL patients with Rai stage 0 stratified by IGHV mutation status and FISH analysis. Black solid line represents 0 unfavorable factors (mutated IGHV and favorable FISH), the red dashed line represents one unfavorable factor and the green dashed line represents two unfavorable factors.