Familial clusters and clinical features, complications, and outcomes in 1000 patients with Waldenström macroglobulinemia

Approximately 20% of patients with Waldenström macroglobulinemia (WM) report family history (FH) of hematologic malignancies. However, the impact of FH on patient outcomes remains unclear. We included 1000 patients with WM to determine the relationship between FH, characteristics, complications, and treatment outcomes. Data collected included clinical features at diagnosis, complications (Bing-Neel syndrome [BNS], aggressive transformation, AL [light chain] amyloidosis, and neuropathy), FH cluster (WM [WM-FH], other B-cell FH [B-FH], non-B-cell FH [NON-B-FH], and sporadic [NO-FH]), and treatment outcomes. Logistic regression models were fitted to estimate the odds of complications. Time-to-event outcomes were assessed using the Kaplan-Meier method, and differences between groups evaluated using the log-rank test. Proportional hazards Cox regression models were fitted to determine the impact of WM-FH on time to first treatment (TTFT), overall survival (OS), and survival after first treatment initiation (SAFTI). The NO-FH group was the reference group for the regression analyses. The median follow-up time from diagnosis was 13 years. There were more women in the WM-FH than in the NO-FH group (50% vs 34%; P< .01). In multivariate logistic regression analysis, WM-FH was associated with higher odds of BNS (odds ratio [OR], 3.90; P = .005) and lower odds of neuropathy (OR, 0.49; P = .03) than NO-FH. The median TTFT was 0.7 years, OS was 23 years, and SAFTI was 20.5 years for all patients. In multivariate Cox regression analyses, WM-FH did not affect TTFT, SAFTI, or OS. Our study suggests higher odds of BNS and lower odds of neuropathy in patients with WM-FH but no impact of WM-FH on TTFT, OS, or SAFTI.