Prognostic Value of Seric Immunoglobulins in CLL: Analysis of 331 Patients with a Median Follow-Up Time of 7.5 Years.

Prognostic value of seric immunoglobulins in CLL has been rarely studied. So we look at all our CLL and we find 331 pts with an initial dosage of IgG, IgA and IgM without M component at diagnosis or during the first year of survey. Ages at diagnosis range from 38 to 93 yrs and median age is 66 yrs. Sex ratio M/F is 1.55 and staging according to Binet’s system notes 264 stages A (188 stages A0), 43 stages B and 24 stages C. IgG levels range from 0.9 to 22.2 g per l with a mean value of 9.38±3.18 g. In logistic regression, IgG level is linked with sex, age, number of lymphoid area according to Binet’s system, blood lymphocytosis and hemoglobin levels used as continuous values. IgA range from 0.1 to 7.8 g (mean value=1.66±1.03 g) and is linked with the same parameters and platelet level too. At least, IgM range from 0 to 3.4 g (mean value=0.78±0.63 g) and is linked with age, number of lymphoid area, blood lymphocytosis and platelet levels. Immunoglobulins levels are also linked with LDH, β2-microglobulin, sCD23 and sCD25 values.

Looking at “corrected” survival after exclusion of not CLL-related deaths including those due to a solid tumor because this complication is independent of initial prognostic factors of CLL, we find that the best cut-off values are 7 g for IgG and 2 g for IgA. For IgG, median survival time is 14.6 yrs for the 268 pts with initial IgG ≥ 7 g versus 6.5 yrs for the 63 other pts (p=0.00004). For IgA, the best cut-off value is 2 g: median survival time is >13.3 yrs for the 100 pts with IgA ≥ 2 g versus 10 yrs for the 231 other pts (p=0.04). These 2 cut-off values are independent and so we can build a prognostic system: 98 pts with IgG ≥ 7 g and IgA ≥ 2 g - 172 pts with IgG < 7 g or IgA < 2 g - 61 pts with low IgG and IgA levels. Median “corrected” survival times of these 3 groups are statistically different: > 13.3, 10.6 and 6.8 yrs (p=0.0009) and when we look at global survival, rates are more different: >13.3, 8.6 and 5.7 yrs (p=0.00009). Same data are noted among stage A patients only and among stage A0 too. So when we opposite this system and with Binet’s and Rai’s classifications, only Rai’s system is ruled out by Cox model looking at “corrected” or global survival. Curiously, this new system has no impact of initiation on treatment among stage A pts while it is linked to evolution to stage C (p=0.05). Finally, we find no correlation with occurrence of an M component or an immunological complication, and also with occurrence of a zoster infection or a Richter syndrome while it is a trend for occurrence of a second neoplasia (p=0.06).