Population-based study on the impact of the familial form of Waldenström macroglobulinemia on overall survival.

Population-based study on the impact of the familial form of Waldenström macroglobulinemia on overall survival Waldenström macroglobulinemia (WM) is a chronic lymphoprolifer-ative disorder (LP) characterized by an immunoglobulin M monoclonal gammopathy in the presence of lymphoplasmacytic lymphoma (LPL) in the bone marrow. 1 We have previously shown in a large population-based study that first-degree relatives of LPL/WM patients had an increased risk of developing LPs. 2 An earlier single-center study on 257 WM patients showed that patients with a family history of WM or other B-cell disorders had a higher bone marrow involvement and were diagnosed at a younger age. 3 Furthermore, WM patients with a family history of a B-cell malignancy (n 5 135) had worse response and shorter progression-free survival when treated with rituximab, compared with patients with sporadic WM. However, patients with familial WM had better response to bortezomib-containing therapy. 4 Through nationwide Swedish registries and a national hematology/ oncology network, we identified 2185 LPL/WM patients diagnosed between 1958 and 2007 and their 6460 first-degree relatives. Our nationwide study is the first, to our knowledge, to estimate the impact of having a family history of B-cell malignancy on overall survival in LPL/WM patients. Family history of any LP was defined as having a first-degree relative with LPL/WM, Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leuke-mia, and/or monoclonal gammopathy of undetermined significance. Overall survival was fitted with the Cox proportional hazard model to obtain hazard ratios (HRs) and 95% confidence intervals (95% CIs), adjusting for sex, age at diagnosis, and year of diagnosis (Table 1). Overall, LPL/WM patients with a family history of any LP had an increased risk of death compared with sporadic LPL/WM patients (HR 5 1.34; 95% CI, 1.03-1.75). The HR for each additive relative diagnosed with any LP was 1.22 (95% CI, 0.99-1.50). Survival differences have not been reported before in familial vs sporadic WM, but these findings are consistent with the earlier single-center study on WM showing worse outcome in familial WM when treated with rituximab. 4 They are, however, in contrast to studies on Hodgkin lym-phoma, non-Hodgkin lymphoma, and chronic lymphocytic leukemia in which familiality was not associated with a poorer outcome. Of individual diseases, with the exception of Hodgkin lymphoma (with only 4 patients), family history of the other LPs showed a nonsignificant trend to increased risk. Female gender was associated with improved survival, which is consistent with earlier findings …