Is B-chronic lymphocytic leukemia (B-CLL) a single entity? Important role of gender in prognostic power of B-CLL tumor distribution pattern points to different type of disease.

Purpose: B-cell chronic lymphocytic leukemia (B-CLL) has highly variable clinical presentation, course and prognosis. This may be due to both different type and/or different stage of the disease. In order to evaluate the impact of tumor cell distribution pattern on clinical course, the prognostic analysis was performed on 722 B-CLL patients (mean age 62.6p ; ; 0.4 ; 64% males). Design and methods: we introduced the model for tumor distribution (TD) assessment based on Total Tumor Mass (TTM) scoring system, where TD value represents percentage of total tumor mass infiltrating peripheral blood and bone marrow (TD=TM1/TTM). TD in B-CLL can be categorized into 3 subgroups: “ pure leukemia” if TD=100%, “ predominantly leukemia” if TD=50%-99% and “ predominantly lymphoma” TD 96, 58 and 43.76 months respectively (p=0.0000). TD parameter significantly correlates with TTM size, Rai and Binet stages, spleen size, beta-2 microglobulin, but failed to correlate with age, lymphocyte count, soluble CD23, and bcl-2/bax ratio. Highly significant association of TD with prognosis was found in overall population of B-CLL patients (p<0.0001). However, to our surprise, both in univariate prognostic analyses and in multivariate Cox analysis the distinction between predominantly leukemia and predominantly lymphoma like distribution is highly significant in female patients (MST 67.5 vs 38.0, p<0.0002), while virtually non-existent in male patients (MST 48 vs. 50, p=0.9, NS). In female patients DT is the strongest independent predictor of prognosis (p=0.000) followed by TTM size (p=0.001), age (p=0.024) and therapy (p=0.069). Conclusions: Tumor mass distribution pattern, a quantitative and simple clinical parameter is independent and strong prognostic parameter in B-CLL. Unexpected finding of substantial difference in prognostic power of DT between genders points out to an interesting, yet unexplained biological impact of gender in pathogenesis of B-CLL. This finding suggests that association of tumor distribution pattern subsets with gender is more likely linked to type then to stage of the disease.