Abstract
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 IGHV3‐21 gene rearrangement which is associated with poor prognosis. The TFS of patients with normal SPE was significantly longer than that of patients with abnormal SPE (log‐rank test: P = 0.0015, with 51% untreated patients at 5.6 years and a perfect plateau afterward vs. a median TFS at 2.64 years for abnormal SPE with no plateau). Multivariate analysis using two different Cox models and bootstrapping showed that normal SPE was an independent good prognostic marker for either Binet stage, lymphocytosis, or IGHV mutation status. TFS was further increased when both normal SPE and mutated 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 SPE could reflect slowly advancing CLL disease. Altogether, our results show that a combination of normal SPE and mutated IGHV genes defines a subgroup of patients with CLL who evolve very slowly and who might never need treatment.
Highlights
Chronic lymphocytic leukemia (CLL), the most frequent indolent B-cell cancer with blood passage of tumor cells in the elderly in western countries, is characterized by a lymphocytosis exceeding five gene mutation (M-CLL) Lymphocytosis (G/L) comprising small circulating monomorphic round B lymphocytes, with constant infiltration of bone marrow and secondary lymphoid organs [1, 2]
The number of patients with lymphocytosis above 30 G/L at diagnosis was significantly lower in patients with normal serum protein electrophoresis (SPE) (14.3% in normal SPE vs. 34.9% in abnormal SPE, Student’s t test: P = 0.017) (Table 1)
We looked at the relationship between SPE and either the immunoglobulin heavy chain gene (IGHV) mutation status or Rossi’s score
Summary
Chronic lymphocytic leukemia (CLL), the most frequent indolent B-cell cancer with blood passage of tumor cells in the elderly in western countries, is characterized by a lymphocytosis exceeding five G/L comprising small circulating monomorphic round B lymphocytes, with constant infiltration of bone marrow and secondary lymphoid organs [1, 2]. CLL is typically characterized by a Matutes score of 4 or 5 [3, Normal SPE detects slowly evolving CLL. Disease progression is heterogeneous with overall survival (OS) ranging from a few years to decades. Because some patients with CLL may have a life expectancy as long as healthy subjects of the same age without treatment while others will rapidly evolve, it has been recognized for a long time that finding reliable prognostic factors is necessary. Patients with Binet Stage A CLL exhibit good treatment-free survival (TFS), with a life expectancy close to that of healthy subjects of the same age. It is well known that the progression of these patients is rather heterogeneous [7]
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