Abstract
Familial chronic lymphocytic leukemia (CLL) constitutes 5% to 7% of CLL and has previously shown a more aggressive pattern of evolution than sporadic CLL, even if no difference in overall survival (OS) has been observed. This multicenter case-control study aimed to compare clinical features, molecular biomarkers, and patient outcomes of familial and sporadic CLL. Adult patients with CLL were enrolled from 18 Italian centers, with familial CLL defined as having at least 1 first-degree relative affected by CLL. Patients with sporadic CLL were matched for biological sex and age at diagnosis within 4 years (1:2 ratio). The Kaplan-Meier method was used to evaluate time-to-event outcomes. Of 480 enrolled patients, 160 had familial CLL and 320 sporadic CLL. Significant clinical and molecular differences between familial and sporadic CLL included the presence of lymphadenopathies at diagnosis >5 cm (7.2% vs 2.8%; P = .027) and unmutated immunoglobulin heavy chain variable gene (55.5% vs 36.2%; P < .001). First- and second-line treatments were required in 55.6% and 46.1% of familial CLL and 43.1% (P = .001) and 29.6% of sporadic CLL (P = .034), respectively. Both time to first treatment (TTFT) and time to next treatment (TTNT) were shorter for familial CLL than for sporadic CLL (median TTFT, 66 months vs 108 months; P = .005; median TTNT, 60 months vs 94 months; P = .030, respectively), although familiarity has not emerged as an independent prognostic factor. No difference in OS was observed. Considering the more aggressive course of familial CLL but similar OS, CLL screening in relatives is not recommended.