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

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Abstract
Recent reports suggest that the expression of germline (GL) Ig variable region heavy‐chain genes (VH) 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 VH 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 VH 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 VH 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 VH 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 VH 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.