Cleaved lymphocytes in chronic lymphocytic leukemia: a detailed retrospective analysis of diagnostic features

Through a global analysis of diagnostic features, the aim was to profile CLL patients with circulating cleaved lymphocytes at diagnosis, a controversial prognostic factor. Although some of them could have been considered today as having Non-Hodgkin's lymphoma, all 106 patients of our retrospective series have had CLL treatments. Slide review distinguished seven lymphocyte morphotypes. With minimal a priori assumptions, excluding in particular clinical staging systems, forty-five diagnostic features were analyzed in 37 patients. CORICO (Correlations Iconography), a purely geometric method, deciphered the multidimensional structure of the raw data. Probabilistic monoparametric tests were made on the 106 patients. In ten patients (Binet stages: 3A, 6B, 1C), at least 8% of the lymphocytes were cleaved. Unrelated to the prolymphocytes, this morphotype had neither links with the CD5+CD23+ (9/10 vs 80/86), FMC7+ (5/10 vs 22/62), CD38 (1/7 vs 7/64) markers nor with any major CLL laboratory values; only three links characterized it: no cases of mixed marrow infiltrate (nodular: 1, interstitial: 6, diffuse: 3; ns), a lower percentage of eosinophils (ns), and predominance of CD11c (7/10 vs 20/66, p < 0.02). In conclusion, in contrast to the PLL morphotype, or to the lactic dehydrogenase (LDH) activity, which was a strong prognostic factor in this series, an independent detrimental value of the cleaved morphotype has not yet been found. Our study shows that free of modeling constraints, this method makes possible a rapid and objective insight into variable interrelations. If further explored in a prospective study, this approach may contribute to the understanding of discrepancies in the literature.