Ig paraprotein in CLL. What does it mean?

Several people have asked whether having a paraprotein in the serum influences the outcome in CLL. A paper in Leukemia Research from China addresses this problem.

They studied 133 patients with CLL, 86 male and 47 female, median age at diagnosis 60 (range, 44–84). They identified 27 patients with Ig paraproteinemia (12 with IgG, 12 with IgM, 3 with both IgG and IgM, but none with IgA), frequency of 20.3%. The median level of serum IgG paraprotein was 28.2 g/l (range, 21.0–62.0 g/l), and IgM paraprotein was 18.1 g/l (range, 2.3–49.1 g/l). The serum monoclonal Ig light chain concordant with the monoclonal Ig light chain expressed by the neoplastic cells in all patients with Ig paraproteinemia.

Strong correlations of serum Ig paraprotein with advanced Binet stage, DAT-positivity, high level of Beta2-MG and TK1, absence of IGHV mutations, ZAP-70-positivity, CD38-positivity, and cytogenetic abnormalities of del(17p13) or del(11q22)were observed.

With a median follow-up of 36 months (range, 4–83 months), 13 patients (9.8%) died. The prognostic factors with statistical significance were considered in a multivariate Cox regression analysis, del(17p13) ZAP-70, and IgM paraproteinemia were the variables strongly associated with survival.

Ig paraproteinemia was associated with poor outcome. Six (22.2%) with Ig paraproteinemia died during the observation period (2 with IgG paraprotein, 2 with IgM paraprotein, 2 patients with both IgG and IgM, respectively), whereas among the 106 patients without Ig paraproteinemia, 7 (6.6%) died. Patients with Ig paraproteinemia had significantly shorter survival times than patients without serum Ig paraprotein.

Bernstein and colleagues], in a study of 111 patients, reported that the presence of serum monoclonal protein in patients with CLL was associated with a shorter median
survival: 63 months for patients with CLL with serum Ig paraprotein compared with 103 months for patients without serum Ig paraprotein. However, Yin and colleagues have not confirmed this observation. The unfavorable prognostic significance of serum Ig paraprotein was observed in this study.

The possible explanations of discrepancy in prognostic impact of serum Ig paraprotein might be different therapeutic regimens, shorter clinical follow-up and smaller number of patients. retained their capability of isotype switching, a process independent of immunoglobulin heavy chain gene mutation. As an alternative, these additional M components may represent biclonal or triclonal ymphoproliferative disorders as described in the literature or the development of a subclone within the original tumor cells due to clonal evolution.

For myself I'm not sure there is anything in this. Perhaps the Chinese population is strange, but this seems a very high incidence of a paraprotein in CLL, which we found at only about 2%. I wonder if in China there is a lymphoplasmacytoid lymphoma that closely resembles CLL.