Normal serum protein electrophoresis and mutated IGHV genes detect very slowly evolving chronic lymphocytic leukemia patients

摘要

More than 35 years after the Binet classification, there is still a need for simple prognostic markers in chronic lymphocytic leukemia (CLL). Here, we studied the treatment‐free survival (TFS) impact of normal serum protein electrophoresis (SPE) at diagnosis. One hundred twelve patients with CLL were analyzed. The main prognostic factors (Binet stage; lymphocytosis; IGHV mutation status; TP53,SF3B1,NOTCH1, and BIRC3 mutations; and cytogenetic abnormalities) were studied. The frequencies of IGHV mutation status, cytogenetic abnormalities, and TP53,SF3B1,NOTCH1, and BIRC3 mutations were not significantly different between normal and abnormal SPE. Normal SPE was associated with Binet stage A, nonprogressive disease for 6 months, lymphocytosis below 30 G/L, and the absence of the style="fixed-case">IGHV3‐21 gene rearrangement which is associated with poor prognosis. The style="fixed-case">TFS of patients with normal style="fixed-case">SPE was significantly longer than that of patients with abnormal style="fixed-case">SPE (log‐rank test: P = 0.0015, with 51% untreated patients at 5.6 years and a perfect plateau afterward vs. a median style="fixed-case">TFS at 2.64 years for abnormal style="fixed-case">SPE with no plateau). Multivariate analysis using two different Cox models and bootstrapping showed that normal style="fixed-case">SPE was an independent good prognostic marker for either Binet stage, lymphocytosis, or style="fixed-case">IGHV mutation status. style="fixed-case">TFS was further increased when both normal style="fixed-case">SPE and mutated style="fixed-case">IGHV were present (log‐rank test: P = 0.008, median not reached, plateau at 5.6 years and 66% untreated patients). A comparison with other prognostic markers suggested that normal style="fixed-case">SPE could reflect slowly advancing style="fixed-case">CLL disease. Altogether, our results show that a combination of normal style="fixed-case">SPE and mutated style="fixed-case">IGHV genes defines a subgroup of patients with style="fixed-case">CLL who evolve very slowly and who might never need treatment.