CLONAL B-CELL LYMPHOCYTOSIS OF MARGINAL ZONE ORIGIN (CBL-MZ): DESCRIPTION OF MAIN CLINICAL FEATURES, DISEASE EVOLUTION AND OUTCOME IN A SERIES OF 100 PATIENTS

Introduction: CBL-MZ has been recognized in WHO classification as a provisional entity. In the present analysis we describe CBL-MZ patients’ (pts) characteristics, disease evolution and prognostic factors for outcome after a long follow-up. Methods: Pts were selected based on the presence of circulating CD5-clonal B-cells with MZ features, without B-symptoms, no evidence of disease elsewhere than the bone marrow (BM), and no cytopenias. Results: 100 consecutive pts were analyzed. The median age was 70y (33-90). Referral reasons: incidental lymphocytosis (77%) or paraproteinemia (13%) or inverted differential (10%). Median # of absolute lymphocyte counts (ALCs) and circulating CBL were 6780/μL (1000-150.000) and 3447/μl (185-145.000), respectively. Elevated LDH and paraproteinemia were found in 10% and 38%, respectively. All but one pts presented BM infiltration by small lymphoid cells (median 30%) with an intrasinusoidal pattern in 1/3 of pts. Immunophenotyping revealed positivity for CD23, CD11c and CD38 in 31%, 43% and 11%, respectively. MYD-88 was positive in 9/84 (11%). The presence of paraprotein was significantly associated with MYD-88 positivity (p<0.0001), lower ALCs (p = 0.002) and CBL (p = 0.001) counts, higher frequency of CD38 expression (p = 0.03) and lymphoplasmacytic differentiation in the BM (p = 0.001). The degree of BM infiltration was associated with the level of ALCs (p = 0.003). At a median follow-up time of 42.3 mos, 30 pts progressed but only 10 required treatment. Progression included: worsening lymphocytosis (17%), cytopenias (4%), splenomegaly (5%), nodal MZL (1%) and increase in paraprotein levels (3%). Therefore, five patterns of disease evolution were recognized (Figure). Treatment was delivered due to cytopenias in 7 pts, symptomatic paraprotein in 1 and bulky splenomegaly in 2. Seven deaths were recorded, one disease related. The median OS was not reached; 5-y time to treatment (TTT) was 91%, and the median time to progression (TTP) 95.6 mos. By univariate analysis ALC ≥median (6780/μL), p = 0.014, CD38+, p = 0.006 and elevated LDH, p<0.0001 were significantly associated with TTP. These factors remained significant at multivariate analysis. We constructed a prognostic model for TTP stratifying pts into 3 risk groups: low-risk - 0 risk factors; intermediate - ALC≥median; high-risk – any of the 2 remaining risk factors or ≥2 factors. Median TTP was 159, 96 and 49 months, for the low-, intermediate and high-risk groups, respectively (p<0.0001). This model was prognostic of TTT, as well, though at a lower level of significance (p = 0.03). Keywords: marginal zone lymphoma (MZL); monoclonal B-cell lymphocytosis (MBL).