Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia

Cellular immunophenotypic studies were performed on a cohort of randomly se lected IgM(+) B-chronic lymphocytic leukemia (B-CLL) cases for which Ig V-H and V-L gene sequences were available. The cases were categorized based on V gene mutation status and CD38 expression and analyzed for treatment hist ory and survival. The B-CLL cases could be divided into 2 groups. Those pat ients with unmutated V genes displayed higher percentages of CD38(+) B-CLL cells (greater than or equal to 30%) than those with mutated V genes that h ad lower percentages of CD38(+) cells (<30%). Patients in both the unmutate d and the greater than or equal to 30% CD38(+) groups responded poorly to c ontinuous multiregimen chemotherapy (including fludarabine) and had shorter survival. In contrast, the mutated and the <30% CD38(+) groups required mi nimal or no chemotherapy and had prolonged survival. These observations wer e true also for those patients who stratified to the Rai intermediate risk category. In the mutated and the <30% CD38(+) groups, males and females wer e virtually equally distributed, whereas in the unmutated and the greater t han or equal to 30% CD38(+) groups, a marked male predominance was found. T hus, Ig V gene mutation status and the percentages of CD38(+) B-CLL cells a ppear to be accurate predictors of clinical outcome in B-CLL patients. Thes e parameters, especially CD38 expression that can be analyzed conveniently in most clinical laboratories, should be valuable adjuncts to the present s taging systems for predicting the clinical course in individual B-CLL cases , Future evaluations of new therapeutic strategies and drugs should take in to account the different natural histories of patients categorized in these manners. (C) 1999 by The American Society of Hematology.