CD49d associates with nodal presentation and subsequent development of lymphadenopathy in patients with chronic lymphocytic leukaemia

Abstract

CD49d is a surface integrin that is expressed on chronic lymphocytic leukaemia (CLL) cells, and strongly correlates with more aggressive disease. Given its association with cell-cell adhesion and leucocyte trafficking, we hypothesized that patients with high CD49d expression would experience a clinical course dominated by lymphadenopathy. CD49d expression was measured by flow cytometry and considered positive if expressed by ≥30% of CLL cells. The study included 797 newly diagnosed CLL/small lymphocytic leukaemia patients; 279 (35%) were CD49d positive. CD49d-positive patients were more likely to present with lymphadenopathy (P < 0·001); a finding that persisted after adjusting for fluorescence in situ hybridisation (FISH) and IGHV mutation status [odds ratio (OR) 2·51; 95% confidence interval (CI) 1·64-3·83; P < 0·001]. Among CLL Rai 0 patients, CD49d positivity was associated with shorter time to development of lymphadenopathy (3·2 years vs not reached, P < 0·01). This association was maintained after adjusting for either FISH [hazard ratio (HR) 2·18; 95% CI 1·25-3·81; P = 0·006) or IGHV status (HR 2·02; 95% CI 1·11-3·69; P = 0·02) individually, but was attenuated when adjusting by both (HR 1·72; 95% CI 0·88-3·38; P = 0·11).These data demonstrate that CD49d-positive CLL patients experience a disease course dominated by lymphadenopathy. These findings could have implications for therapy selection and disease monitoring.

Keywords: CD49d; chronic lymphocytic leukaemia; lymphadenopathy; small lymphocytic lymphoma.

Fig 1

Association between CD49d expression at time of diagnosis and type of CLL presentation. The percentage of lymphocytes expressing CD49d is shown on the y-axis (each bar shows median, first, and third quartiles). (A) By Rai stage; (B) By lymphadenopathy. CLL, chronic lymphocytic leukaemia; LN, lymphadenopathy; SLL, small lymphocytic leukaemia; w/o, without.

Fig 2

Time from diagnosis to lymphadenopathy development by CD49d negative (<30% expression), CD49d positive (>30% expression) among newly diagnosed chronic lymphocytic leukaemia patients presenting with Rai stage 0 disease.