Chronic lymphocytic leukemia in the elderly: clinico-biological features, outcomes, and proposal of a prognostic model

Abstract

We investigated the clinico-biological features, outcomes, and prognosis of 949 patients with chronic lymphocytic leukemia according to age. No biological differences (cytogenetics by fluorescent in situ hybridization, IGHV, ZAP-70, CD38, NOTCH1, SF3B1) were found across age groups. Elderly patients (>70 years; n=367) presented more frequently with advanced disease (Binet C/Rai III-IV: 10/12% versus 5/5%; P<0.001), were treated less frequently (23.8% versus 41.9% at 3 years; P<0.001) and in most cases did not receive highly effective regimens and thus had a lower overall response rate (49% with 14% having complete responses versus 69% with 31% having complete responses; P<0.001). The elderly patients also had a shorter overall survival (6.6 versus 13.3 years; P<0.001) and higher disease-unrelated mortality (34.9% versus 6.9% at 10 years; P<0.001). However, disease-attributable mortality was not significantly different between younger and older patients. A combination of Binet stage, ZAP-70 level, β2-microglobulin concentration and comorbidity identified two risk groups (low-risk: 0-1 parameters; high-risk: 2-4 parameters) with different overall survivals (median: 6.8 versus 11.4 years, P<0.001). In patients requiring treatment, comorbidity at treatment (Cumulative Illness Rating Scale-T>4; hazard ratio 2.2, P<0.001) and response (treatment failure versus response: hazard ratio 1.60, P<0.04) were the most important prognostic factors for overall survival. In conclusion, in our series, elderly patients with chronic lymphocytic leukemia did not present with any biological features distinct from those of younger patients, but did have a poorer clinical outcome. This study highlights the importance of comprehensive medical care, achieving response to therapy, and specific management strategies for elderly patients with chronic lymphocytic leukemia.

Figure 1.

Overall survival of the (A) whole series (median 9.7 years), and (B) according to age groups (<70 vs. ≥70 years) in patients with CLL (median 6.6 vs. 13.3 years; P<0.001).

Figure 2.

Estimates of overall survival since diagnosis for patients with CLL >70 years based on (A) Binet clinical stage (A, B, C) (median 7.2 vs. 4.9 vs. 2.1 years; P<0.001), (B) serum levels of β2-microglobulin (B2M) (median 10.2 vs. 6.2 years; P<0.001), (C) ZAP-70 expression (median 9.4 vs. 7.7 years; P<0.001), and (D) comorbidity assessed by CIRS at diagnosis (CIRS-D) (median 7.7 vs. 6.7 years; P=0.064). Univariate analysis was performed using the Kaplan-Meier method and log-rank test; P<0.05.

Figure 3.

Two different prognostic groups (low vs. high risk with median survivals of 11.4 vs. 6.8 years; P<0.001) of elderly patients with CLL based on four parameters of independent prognostic value for overall survival by multivariate analysis (advanced Binet clinical stage, increased levels of B2M, high expression of ZAP-70 and CIRS-D >6).