Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia

Recent reports suggest that the expression of germline (GL) Ig variable region heavy-chain genes (V_H) is a negative prognostic factor for B-cell chronic lymphocytic leukaemia (B-CLL) patients and that CLL B-cell CD38 expression may be a surrogate marker of Ig V_H gene status. Currently, however, the usefulness of this surrogate marker is controversial. Therefore, our goal was to study the ability of CD38 to act as a surrogate marker for Ig V_H somatic mutation (SM), and to identify differences in overall survival (OS), progression-free survival (PFS) and response in B-CLL patients based on these two markers. We first assessed the relationship between CD38 expression and Ig V_H status on 131 B-CLL patients, including 66 patients enrolled in three North Central Cancer Treatment Group Trials. Although the mean percentages of CD38⁺ clonal B cells were significantly higher for patients classified as GL versus SM, CD38 was not a reliable marker for clonal B-cell SM. Overall, GL patients exhibited significantly shorter OS and PFS times than SM patients. Despite the inability of clonal B-cell CD38 expression to predict Ig V_H mutation status, patients with ≥ 30% CD38⁺ cells did have shorter PFS and OS times than did CLL patients with < 30% CD38⁺ cells. Thus, the relationship between CD38 expression and Ig V_H mutation status in B-CLL is not straightforward. Nevertheless, analysis in a co-operative group clinical trial setting suggests that both B-cell markers alone or in combination may have clinical usefulness. These data strongly encourage the study of these biological markers as they relate to disease heterogeneity in B-CLL.