VITAMIN D Insufficiency Affects Time to FIRST TREATMENT (TFT) In EARLY CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Abstract 4601

Recent data suggest that vitamin D insufficiency is related to inferior prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated whether 25(OH)D serum levels affect time to first treatment (TFT), a disease-specific end point, in 130 previously untreated CLL patients with early disease (i.e., Binet stage A). Measurement of 25(OH)D was conducted by means of a direct, competitive chemiluminescence immunoassay using the DiaSorin LIAISON 25(OH)D TOTAL assay (DiaSorin, Inc., Stillwater, Minnesota). Levels of 25(OH)D did not reflect Rai substages (P=0.27), Beta2-microglobulin (P=0.52), absolute lymphocyte count (P=0.21), FISH chromosome abnormalities (P=0.11), mutational status of IgVH (P=0.43), ZAP-70- (P=0.53) or CD38-expression (P=0.82).Overall, 42 patients (31.8%) had severe vitamin D insufficiency (< 10 ng/mL), 66 (50%) had mild to moderate insufficiency (10–24 ng/mL), and 24 (18.1%) had 25(OH)D levels within the optimal range(25–80 ng/mL), with no relationship between the month of sample collection and 25(OH)D level (P=0.188). A patient stratification according to these 3 groups led to significant difference in terms of TFT, with vitamin D insufficient patients having the shortest TFT (P=0.02). With respect to continuous 25(OH)D levels and clinical outcome, TFT was shorter as 25(OH)D decreased until a value of 13.5 ng/mL at which point the association of 25(OH)D and TFT remained constant. As a matter of fact, the 25(OH)D value of 13.5 ng/mL identified two patients subsets with different TFT risk (HR=1.91; 95%CI=1.06–3.44;P=0.03). In multivariate analysis the variable entering the model at a significant level were mutational status of IgVH (P<0.0001), serum thymidine kinase ((P=0.02) and absolute lymphocyte count (P=0.03). Thus confirming the Mayo clinic experience, our data provide further evidence that 25(OH)D levels may be an important host factor influencing TFT of Binet stage A patients. Since the effect of 25(OH)D insufficiency may be may be relevant in this subset of patients who are generally observed for years before starting therapy future trials should address the role of vitamin D therapy in delaying disease-progression.