Regional Standardization of CLL Management: Results of a Delphi Consensus Process

The therapeutic landscape of chronic lymphocytic leukemia (CLL) has been profoundly transformed by the introduction of Bruton tyrosine kinase and BCL-2 inhibitors. Despite improved survival outcomes, treatment selection remains complex, particularly in older patients with comorbidities, frailty, and increased infectious vulnerability. To address areas of clinical heterogeneity and support real-world decision-making, a two-round Delphi consensus process was conducted among 15 hematologists from 15 hematology departments across two Italian regions, Calabria and Sicily. A steering committee developed 12 statements covering key clinical and organizational aspects of CLL management, including infectious risk assessment, frailty evaluation, and the role of TP53 alterations in therapeutic choice. Agreement was assessed using a four-point Likert scale, with consensus predefined as ≥ 70% agreement or disagreement. All invited clinicians participated in both rounds (100% response rate). In the first round, consensus was achieved for 8 of 12 statements (66.7%). Following reformulation of unresolved items, two additional statements reached consensus in the second round. Overall, strong agreement was observed for five statements, while moderate convergence persisted for others. Panelists emphasized that infectious risk assessment should systematically inform treatment decisions and that structured frailty tools, including ECOG Performance Status and the Clinical Frailty Scale, may improve patient stratification. Although TP53 alterations were recognized as critical biological determinants, therapeutic decisions in older patients should balance genetic risk with age, comorbidities, frailty, and socioeconomic context. This regional initiative highlights priorities for patient-centered, multidimensional CLL management and may inform the development of optimized care pathways within coordinated regional networks.