Serum Adiponectin Compared with ZAP-70, CD38 and Immunoglobulin Heavy-Chain Mutation Status as a Predictor of Time to First Treatment in Early B-Cell Chronic Lymphocytic Leukemia.

We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia [CLL] (i.e, mutational status of the immunoglobulin heavy chain variable region [IgV_H], ZAP-70- and CD38-expression) and serum levels of adiponectin by evaluating the impact of these variables on the time to first treatment [TFT] in a series of 69 previously untreated Binet stage A B-cell CLL patients. Higher levels of adiponectin inversely correlated with peripheral blood lymphocytosis (r=−0.254; P=0.03), male gender (P=0.0002), percentage of ZAP−70-positive (r=− 0.285; P=0.04) and CD38-positive (r=−0.294; P=0.04) B-CLL cells.

After a median follow-up time of 32 months (range, 2–120 months) 28 (40.5%) out of 69 patients experienced a need for chemotherapy. Kaplan-Meier estimates of patients’ TFT, plotted after searching the best cut-off for adiponectin (i.e., 5.88 μg/mL ), demonstrated that low adiponectin concentration was associated with a shorter TFT (median TFT 32 months; P=0.01). The relationship among the various bio-pathological parameters, analyzed by the multiple correspondence analysis (MCA), showed two different clinico-biological profiles. The first, characterized by higher adiponectin serum levels (i.e., > 5.88 μg/mL), higher platelet count (> 174 x 10⁹/L), lower β₂-microglobulin [β₂-m] (< 2.35 mg/L), presence of mutation in the IgV_H and low percentage of either CD38-positive (< 20%) or ZAP-70-positive (< 20%) B-CLL cells, was associated with a stable pattern of disease generally not requiring therapy. The second, defined by lower adiponectin levels, lower platelet count, high β₂-m concentration, absence of mutation in the IgV_H, high percentage of CD38- and ZAP-70 positive B-cells, was associated with a more progressive pattern of disease and a shorter TFT. The univariate Cox proportional hazard model demonstrated that in addition with lower serum levels of adiponectin (Hazard Ratio [HR], 2.936; P=0.01), the absence of IgV_H mutational status (HR, 6.378; P=0.002) and ZAP-70-positivity (HR, 3.314; P=0.02) were associated with a shorter TFT. However, in multivariate analysis only ZAP-70 positivity emerged as predictor of the TFT (HR, 5.187; P=0.008).

Our results indicate that in early B-cell CLL clinico-biological profile including among other parameters adiponectin may provide a useful insight into the complex interrelationship of prognostic variables and semplify their interpretation. However, adiponectin may not replace the need for the determination of ZAP-70 and IgV_H mutational status.