title: Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families.
abstract: OBJECTIVE
  Because the clinical significance of immunoglobulin abnormalities reported in relatives of familial Waldenström macroglobulinemia (WM) patients is unknown, we initiated a follow-up study of three WM families originally evaluated 27 years previously.
  
  
  METHODS
  Of 29 eligible first-degree relatives of WM patients, 27 (93%) had originally participated in clinical and electrophoretic evaluations. We re-contacted all participants for prospective follow-up electrophoretic analysis and other studies.
  
  
  RESULTS
  Initially, five relatives had IgM monoclonal gammopathy (IgM MG), and four had IgM polyclonal gammopathy (PG). Twenty-two relatives (81%) were re-evaluated. Median follow-up was 17 years (range, 7-27). At re-contact, all IgM MG persisted or progressed, including three that evolved to WM. Among the four with PG, two new IgM MG cases developed. Overall, seven relatives (26%) had IgM MG, and five (18%) had IgM PG.
  
  
  CONCLUSIONS
  Although based on small numbers, this study provides the longest comprehensive follow-up of WM families to date. IgM MG seems to be a phenotypic marker of WM susceptibility in some families and may have a high risk of progression to WM. IgM PG may also be important in WM families. These observations require validation in larger studies and, if confirmed, may be used to identify a cohort (relatives with IgM MG) for future prevention strategies.
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NIH, Department of Health and Human Services, 6120 Executive Boulevard, MSC 7236. Bethesda, MD 20892-7236, USA. mcmastem@mail.nih.gov
authors.forename: Mary L
authors.initials: ML
authors.lastname: McMaster
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Csako
authors.forename: Therese R
authors.initials: TR
authors.lastname: Giambarresi
authors.forename: Linda
authors.initials: L
authors.lastname: Vasquez
authors.forename: Melissa
authors.initials: M
authors.lastname: Berg
authors.forename: Stephanie
authors.initials: S
authors.lastname: Saddlemire
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hulley
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005190:Family; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000235:genetics; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics* / Q000276:immunology