Correlation of high CD49d expression with disease progression and need for therapy in chronic lymphocytic leukemia (CLL) patients

Abstract

7091 Background: CD49d mediates interaction of lymphocytes with microenvironmental components. We and others reported the correlated expression of CD49d and CD38 by CLL cells, and the complementary value of these molecules in predicting overall survival for CLL patients. However, nothing is known on the relationship of CD49d with other prognosticators and its impact in predicting disease progression and need for therapy in CLL. Methods: The study includes 232 CLLs (median age 64 yrs), all characterized for Rai stages, lymphocyte doubling time (LDT), CD49d, CD38 and ZAP-70 expression, serum levels for sCD23 and beta2-microglobulin (beta2-m), IgVH mutations (139/232), cytogenetics (151/232; FISH for 17p, 11q, 13q, 12). CD49d was measured in CD19/CD5 cells by three-color flow cytometry, choosing a 30% cut-off to discriminate CD49d-low vs. CD49d-high CLLs. NCI-working group criteria were used for CLL diagnosis, progression and therapy need. Results: Median time-to-progression (TTP) was 136 and 56 months in CD49d-low and CD49d-high CLL patients (p=0.00008), respectively; similarly, median time-to-treatment (TTT) was 108 and 46 months for the same patient groups (p=0.000008). Correlations were also observed among CD49d and CD38 (p=2.2x10exp-16) or ZAP-70 (p=0.00009) expression, sCD23 serum level (p=0.0017), LDT (p=0.0037), Rai stages (p=0.019), cytogenetics (p=0.011), IgVH mutations (p=0.00008). TTT and TTP were significantly shorter in CLLs in advanced Rai stages, or with high CD38 and ZAP-70 or low IgVH mutations. Within these cases, significantly longer TTP/TTT were observed in subsets expressing low CD49d. Serum levels of sCD23 and beta2-m, LDT, and FISH analyses had also predictive value for progression and treatment in our series. Within the better prognosis groups (i.e. <70 U/ml sCD23, 12 months, or a normal karyotype), high CD49d expression identified a subset of patients with significantly shorter TTP/TTT. Overall, the capability of CD49d to predict disease progression and need for therapy was statistically significant in younger patients (<64 y.o.; 115 cases; p=0.0001), but not in those older than 64 yrs (117 cases; p=0.09). Conclusions: We propone to include evaluation of CD49d expression in the prognostic assessment of CLL patients. No significant financial relationships to disclose.