title: Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003).
abstract: Current information on Waldenström macroglobulinemia (WM) is based on retrospective or single-institution studies of patients requiring therapy. Between 1992 and 1998, 231 patients with WM were enrolled in a prospective observational multicenter clinical trial. Of these, 182 patients with symptomatic or progressive disease were treated with 4 to 8 cycles of therapy with a purine nucleoside analogue, fludarabine (FAMP; 30 mg/m(2) of body-surface area daily for 5 days every 28 days). A serum beta2-microglobulin (beta2M) level below 3 mg/L and a hemoglobin level of at least 120 g/L (12 g/dL) at presentation predicted a lower likelihood of requiring therapy. The overall rate of response to FAMP therapy was 36% (95% confidence interval, 29%-44%), with 2% complete remissions. Patients who were 70 years old or older had a substantially lower likelihood of response (odds ratio, 0.34; P =.004) than younger patients. On multivariate analysis, a serum beta2M level of 3 mg/L or higher, hemoglobin level below 120 g/L, and serum IgM level below 40 g/L [4 g/dL] were significant adverse prognostic factors for survival. We developed a simple staging system for WM by using these variables and identified 4 distinct subsets of patients with estimated 5-year overall survival rates of 87%, 64%, 53%, and 22%, and 5-year progression-free survival rates of 83%, 55%, 33%, and 12%. Prognosis in WM is highly variable and serum beta2M was the dominant predictor of a need for therapy and of survival. FAMP has activity against WM. Our staging system may provide guidance for a risk-based approach to the treatment of WM.
authors: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY, USA.
authors: M V
authors: MV
authors: Dhodapkar
authors: J L
authors: JL
authors: Jacobson
authors: M A
authors: MA
authors: Gertz
authors: S E
authors: SE
authors: Rivkin
authors: G D
authors: GD
authors: Roodman
authors: J M
authors: JM
authors: Tuscano
authors: M
authors: M
authors: Shurafa
authors: R A
authors: RA
authors: Kyle
authors: J J
authors: JJ
authors: Crowley
authors: B
authors: B
authors: Barlogie
mesh_terms: D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008954:Models, Biological; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D006454:Hemoglobins; D007075:Immunoglobulin M; D001613:beta 2-Microglobulin; D014740:Vidarabine; C024352:fludarabine