ABSTRACTnosis was estimated by calculation of the creatinine clearance using the Modification of Diet in Renal Disease (MDRD) formula. For patients aged ≥70 years, the Cumulative Illness Rating Scale (CIRS) was retrospectively assessed at the time of diagnosis (CIRS-D) and first-line treatment (CIRS-T).12,13 The assessment of the CIRS is detailed in the Online Supplementary Appendix.

We investigated CD49d (also termed ITGA4) expression and its biological and clinical correlations in 415 patients with chronic lymphocytic leukaemia. CD49d expression was stable over the course of the disease. A high expression of CD49d (>30%) was found in 142/415 (34%) patients and was associated with progressive disease (advanced clinical stage, high serum lactate dehydrogenase or β2 -microglobulin levels; all p < 0·05) and aggressive disease biology (increased ZAP70 or CD38, unmutated IGHV, trisomy 12, mutations of NOTCH1 and SF3B1; all P < 0·05). A higher CD49d expression was also associated with a lower blood lymphocyte count and a higher number of lymphoid areas involved by the disease. Patients with high CD49d 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 CD49d expression. However, no significant differences in response rates were observed. In the subgroup of patients with mutated IGHV, high CD49d expression was predictive of a shorter TTT while other markers, such as ZAP70 and CD38, were not. In conclusion, in this study CD49d expression correlated with high-risk CLL biomarkers and proved to be useful for separating patients with mutated IGHV into two different prognostic groups.

ABSTRACTdeletion have a higher probability of remaining MRD-positive after therapy compared to patients without this chromosome abnormality.18 For all these reasons, current guidelines for the management of patients with CLL recommend MRD assessment only within clinical trials with "curative intention". 36

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