CD 49d ( ITGA 4) expression is a predictor of time to first treatment in patients with chronic lymphocytic leukaemia and mutated IGHV status

We investigated CD 49d (also termed ITGA 4) expression and its biological and clinical correlations in 415 patients with chronic lymphocytic leukaemia. CD 49d expression was stable over the course of the disease. A high expression of CD 49d (>30%) was found in 142/415 (34%) patients and was associated with progressive disease (advanced clinical stage, high serum lactate dehydrogenase or β 2 ‐microglobulin levels; all p < 0·05) and aggressive disease biology (increased ZAP 70 or CD 38, unmutated IGHV , trisomy 12, mutations of NOTCH 1 and SF 3B1 ; all P < 0·05). A higher CD 49d expression was also associated with a lower blood lymphocyte count and a higher number of lymphoid areas involved by the disease. Patients with high CD 49d expression were treated more frequently (55% vs. 27%; P < 0·001) and earlier (median time to treatment [ TTT ] 65·4 months vs. not reached; P < 0·001) than those with low CD 49d expression. However, no significant differences in response rates were observed. In the subgroup of patients with mutated IGHV , high CD 49d expression was predictive of a shorter TTT while other markers, such as ZAP 70 and CD 38, were not. In conclusion, in this study CD 49d expression correlated with high‐risk CLL biomarkers and proved to be useful for separating patients with mutated IGHV into two different prognostic groups.