<i>SLC28A3 </i>expression and fludarabine-emergent autoimmune hemolytic anemia in chronic lymphocytic leukemia: A new player in an old equation

Fludarabine treatment in patients with chronic lymphocytic leukemia (CLL) has been associated with immune dysregulation and the development of autoimmune hemolytic anemia (AIHA). Prior research indicates a potential correlation between the expression of the SLC28A3 gene, which encodes human concentrative nucleoside transporter 3 (responsible for fludarabine uptake), and treatment response. This retrospective study investigated the relationship between baseline SLC28A3 expression levels, quantified via reverse-transcriptase polymerase chain reaction (qRT-PCR), and the incidence of AIHA in a cohort of CLL patients receiving fludarabine and cyclophosphamide (FC) therapy. Patients were categorized into two groups: "FC-emergent AIHA," encompassing patients who developed AIHA during or following FC therapy, and "no FC-emergent AIHA," which included patients with pre-existing AIHA prior to any treatment and those who remained AIHA-free throughout follow-up. A comparative analysis of these groups revealed no significant differences in most clinical and biological variables. However, a statistically significant difference was observed in median baseline SLC28A3 expression, which was sevenfold lower in the "FC-emergent AIHA" group compared to the "no FC-emergent AIHA" group. Furthermore, SLC28A3 expression did not significantly correlate with most of the other clinical or biological parameters, including time to first treatment or overall survival. These findings suggest that diminished baseline SLC28A3 expression may correlate with an elevated risk of fludarabine-emergent AIHA in CLL patients. Further validation through larger, prospective cohorts is essential to confirm the predictive utility of SLC28A3 expression for optimizing fludarabine-based therapeutic strategies.