Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families.
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.
McMaster
Mary L
ML
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
Csako
Gyorgy
G
Giambarresi
Therese R
TR
Vasquez
Linda
L
Berg
Melissa
M
Saddlemire
Stephanie
S
Hulley
Benjamin
B
Tucker
Margaret A
MA
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