A proliferation-inducing ligand (APRIL) serum levels predict time to first treatment in patients affected by B-cell chronic lymphocytic leukemia

Purpose: A proliferation‐inducing ligand (APRIL), a tumor necrosis factor superfamily member involved in B‐lymphocytes differentiation and survival, plays a role in protecting B‐Cell Chronic lymphocytic leukemia (B‐CLL) cells from apoptosis. Having observed that APRIL serum (sAPRIL) levels were higher in B‐CLL patients with CLL at diagnosis as compared to healthy donors (14.61 ± 32.65 vs. 4.19 ± 3.42 ng/mL; P < 0.001), we tested the correlation existing in these patients between sAPRIL, clinical–biological parameters and disease progression. Experimental design: sAPRIL levels were measured by ELISA in 130 patients with B‐CLL at diagnosis and in 25 healthy donors. Results: sAPRIL levels did not correlate with gender, age, clinical stage, blood cell counts, β2‐microglobulin (β2M) levels, ZAP‐70 and CD38 expression. Using median sAPRIL natural logarithm (ln) as cutoff, we distinguished two groups of patients (APRIL_LOW and APRIL_HIGH) who were comparable with regard to clinical–biological parameters and overall survival, but different with regard to time to the first treatment (TTFT; P = 0.035). According to univariate analysis, high lymphocyte count, high β2M, Binet stage B–C, ZAP‐70 expression and ln(sAPRIL) above median were associated with earlier TTFT. Advanced clinical stage, high β2M, ZAP‐70 expression and ln(sAPRIL) above median remained independently predictive of shorter TTFT at multivariate analysis. Moreover, sAPRIL increased its prognostic significance when patients were stratified according to independent favorable clinical–biological characteristics (low β2M, stage A and lack of ZAP‐70 expression). Conclusions: sAPRIL is a novel indicator of shorter TTFT in B‐CLL and a predictor of progression especially in patients otherwise considered at low risk according to validated prognostic factors.