[1172] Evaluation of 6q Deletion in Waldenstrom's Macroglobulinemia, a Multicenter Collaborative Study

H Chang, C Qi, Y Trieu, A Jiang, W Xu, D Reece, C Chen, KH Young, A Chesney, P Jani, C Wang, R Padmore. University Health Network, Toronto, Canada; University of Wisconsin, Wisconsin; Sunnybrook Health Sciences Center, Toronto, Canada; Thunder Bay Health Sciences Center, Thunder Bay, Canada; Mount Sinai Hospital, Toronto, Canada; Ottawa General Hospital, Ottawa, Canada

Background: Waldenstrom macroglobulinemia (WM) is a rare clinical syndrome characterized by a clonal lymphoplasmacytic bone marrow infiltrate and a serum IgM paraprotein. The deletion of the long arm of chromosome 6 (del (6q)) is the most common cytogenetic abnormality in WM, but its prognostic significance is unclear.
Design: A total of 89 cases diagnosed with WM from the participating institutions were entered into the study. Lymphoplasmacytic cells from bone marrow aspirates of the patients were assessed for 6q deletions by interphase fluorescence in situ hybridization (FISH) with 6q21 and 6q25 probes. Clinical and laboratory data were reviewed.
Results: Overall, interphase FISH detected hemizygous 6q deletions in 37 (41.6%) of the 89 WM cases. The 6q21 locus was deleted in 31 (34.8%) of 89 cases, and 6q25 in 25 (33.8%) of 74 cases. Both 6q21 and 6q25 were deleted in 19 (51%) of 37 deleted cases. Patients with 6q deletions had higher C-reactive protein levels than non-deleted patients (p= 0.02). There was no correlation between del (6q) and other biological factors such as age, gender, hemoglobin, platelet count, viscosity, beta-2 microglobulin, albumin, IgM level and degree of bone marrow lymphoplasmacytic infiltration. The median follow-up was 57.5 months with median overall survival of 163 months and a 10-year survival rate of 63%. Twenty-eight (93%) of 30 patients with 6q deletion received treatment, while 32 (80%) of the 40 patients without the deletion were treated (p=0.17). There was no significant difference in time to the initial treatment between deleted and non-deleted groups (median 5.6 months vs. 2.6 months, p=0.46), or overall survivals in patients with and without del (6q) (163 months vs. not reached, p= 0.83).
Conclusions: Our data indicat that 6q deletions are frequently detected in WM but do not appear to influence the clinical outcome. The 6q deletion extends beyond 6q21 to involve at least the 6q25 locus. Further studies with clinical trials and longer follow-up are indicated to confirm its prognostic relevance, identify the minimal deleted region on 6q, and search for candidate tumor suppressor gene(s) potentially involved in the pathogenesis of WM.
Category: Hematopathology

Tuesday, March 10, 2009 9:30 AM

Poster Session III # 124, Tuesday Morning