RESUMO
BACKGROUND: Familial clustering of B-cell disorders among Waldenström's macroglobulinemia (WM) patients has been reported, though the frequency and any differences in disease manifestation for familial patients remain to be defined. PATIENTS AND METHODS: We therefore analyzed clinicopathological data from 257 consecutive and unrelated WM patients. Forty-eight (18.7%) patients had at least one first-degree relative with either WM (n = 13, 5.1%), or another B-cell disorder including non-Hodgkin's lymphoma (n = 9, 3.5%), myeloma (n = 8, 3.1%), chronic lymphocytic leukemia (n = 7, 2.7%), monoclonal gammopathy of unknown significance (n = 5, 1.9%), acute lymphocytic leukemia (n = 3, 1.2%) and Hodgkin's disease (n = 3, 1.2%). Patients with a familial history of WM or a plasma cell disorder (PCD) were diagnosed at a younger age and with greater bone marrow involvement. RESULTS: Deletions in 6q represented the only recurrent structural chromosomal abnormality and were found in 13% of patients, all non-familial cases. Interphase FISH analysis demonstrated deletions in 6q21-22.1 in nearly half of patients, irrespective of familial background. CONCLUSIONS: The above results suggest a high degree of clustering for B-cell disorders among first-degree relatives of patients with WM, along with distinct clinical features at presentation based on familial disease cluster patterns. Genomic studies to delineate genetic predisposition to WM are underway.
