DP054 | INFECTIONS, SECOND PRIMARY MALIGNANCIES AND AUTOIMMUNE DISEASES IN MONOCLONAL B-CELL LYMPHOCYTOSIS AND EARLY-STAGE CHRONIC LYMPHOCYTIC LEUKEMIA: INSIGHTS FROM A RETROSPECTIVE COHORT OF A TERTIARY CARE CENTRE

Background. Monoclonal B-cell Lymphocytosis (MBL) is a premalignant phase of Chronic Lymphocytic Leukemia (CLL), defined by less than 5x10^9 clonal B-cells/L in the peripheral blood of otherwise healthy individuals. MBL is further classified into low-count (LC-MBL) (< 0.5x10^9 clonal B-cells/L) and high-count (HC-MBL) subgroups. While CLL-associated risks of infections, second primary malignancies (SPM), and autoimmune diseases (AD) are well documented, the incidence of these conditions in MBL patients is less understood. Aim. The primary aim of this study was to investigate potential differences in the incidence of infections, SPMs, and ADs between MBL CLL-like and early-stage CLL patients. Methods. We analysed 200 MBL patients (of which 114 HC-MBL and 20 LC-MBL) diagnosed between 2004-2024 at the University of Padua Hematology Unit (Italy) and subsequently a matched cohort of 200 early-stage CLL patients was selected. The prevalence of ADs was compared with the χ2 test, the cumulative incidence (CI) of SPMs was evaluated with the Fine and Grey’s method, and infection incidence was assessed with an Andersen-Gill model, accounting for recurrent events and care intensity. Results. The features of patients are reported in Table 1. After a median follow-up of almost 10 years, 88 MBL progressed to CLL (3 LC-MBL vs 85 HC-MBL) and 39 started a therapy (1 LC-MBL vs 38 HC-MBL), while 78 CLL patients required treatment. AD prevalence was 23% (46 patients) in the MBL group and 22.5% (45) in the CLL group (p 0.91), with autoimmune thyroiditis being the most frequent in both groups (45.7% in MBL vs 42.2% in CLL groups). The 10-years CI of SPMs was similar in both groups, 13% for MBL and 16% for CLL individuals (p 0.80). The most frequent SPMs were solid tumors (61.3% of 31 patients with MBL vs 66.7% of 33 individuals with CLL, who developed a SPM), with pulmonary cancer being the most prevalent in MBL patients (6) and colon cancer in CLL patients (8). The risk of infections is 2-fold higher in patients with CLL compared to those with MBL (HR 1.49-3.04 p <0.001), while no significant difference was found between the two MBL subgroups (HR 0,153-1,08 p 0.058). Discussion. We found that early-stage CLL patients have a higher risk of infections, but not ADs or SPMs compared to the MBL group, while no difference emerges comparing the two MBL subgroups. Our preliminary data suggest that immune dysfunction in CLL may develop as early as the premalignant stage of MBL, although further multicentre prospective studies are needed.