Bone Marrow Tumor Burden as a Predictor of Time to Progression in Asymptomatic Waldenstrom Macroglobulinemia: Evidence from a 20- year Follow-up Italian Cohort

While data suggest that bone marrow (BM) disease burden in asymptomatic Waldenström Macroglobulinemia (WM) may be related to time to progression, no consensus has yet been reached regarding the optimal thresholds. A 25% BM infiltration threshold was used to stratify our cohort of 150 asymptomatic WM into high- and low-disease burden subgroups. The primary outcomes evaluated were time to progression (TTP) and overall survival (OS). We found that the high BM tumor burden subgroup exhibited distinct clinical and biological features, including lower hemoglobin levels, higher serum IgM concentrations, increased monoclonal component levels, higher frequency of CXCR4 mutations, and a lower prevalence of peripheral neuropathy. This subgroup also demonstrated significantly shorter median TTP compared with patients with lower BM involvement (64 months vs. 137 months, p = 0.01). Factors associated with shorter TTP included advanced age (hazard ratio [HR] 1.04), lower hemoglobin levels (HR 1.02), elevated serum MC (HR 1.06), increased IgM concentrations (HR 1.06), and the presence of cytogenetics aberrations (HR 2.5). In multivariate analysis, only elevated serum IgM (HR 1.09) remained an independent predictor of shorter TTP, whereas cytogenetic abnormalities showed only a trend toward significance (HR 2.4). In the OS analysis, no significant differences were observed between the two subgroups. Finally, a higher BM tumor burden at diagnosis is associated with shorter TTP in asymptomatic WM. Elevated serum IgM independently predicted inferior TTP. Our results are consistent with previously published series and the 5 ^th WHO Lymphoid Neoplasm Classification, underscoring the prognostic significance of BM disease burden in WM.