Analysis of Stereotyped B-Cell Receptor Frequencies Among Portuguese De Novo-Diagnosed Chronic Lymphocytic Leukemia Patients (PAIS Study).

BACKGROUND/OBJECTIVES: Chronic lymphocytic leukemia (CLL) exhibits a heterogeneous clinical course influenced by genetic factors, such as the mutational status of immunoglobulin variable regions (). Recently, B-cell receptor (BcR) stereotypes have shown promising prognostic value, potentially surpassing status. The PAIS study analyzed BcR stereotypes and mutations in newly diagnosed Portuguese CLL patients to assess prognostic characteristics and disease progression.

METHODS

This cross-sectional study included 463 adult patients from 15 Portuguese centers, recruited between November 2020 and September 2023. The median age at diagnosis was 70.4 years. The most common clinical stages were 0 (54%) and 1 (32.83%).

RESULTS

A total of 15 different BcR stereotypes were identified in the cohort studied. Subtype #1, associated with a poorer prognosis, was the most prevalent, observed in 3.90% of newly diagnosed Portuguese CLL patients. Considering the 19 major stereotypes that could be assigned by the ARResT subsets tool, most patients exhibited a heterogeneous BcR profile (90.14%). A total of 57.24% of patients had mutated . The concentration of β2-microglobulin was significantly lower in patients with mutated (2.6 mg/L vs. 3.6 mg/L, < 0.001). Clinical stage, assessed by the RAI staging system, differed between subgroups, with a higher frequency of stage 0 in patients with mutated and stage 2 in unmutated patients ( = 0.009).

CONCLUSIONS

The PAIS study highlighted the predominance of a heterogeneous BcR profile in Portuguese CLL patients. The higher percentage of patients with mutated at diagnosis supports prior findings. This study improves the characterization of the 10% of Portuguese CLL patients with major BcR stereotypes, offering healthcare providers better predictive power for disease progression and potentially impacting clinical decision making.