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Head of Westport, MA, United States

Kumar S.,Mayo Medical School | Zhang L.,ECOG | Dispenzieri A.,Mayo Medical School | Van Wier S.,Mayo Medical School | And 9 more authors.
Leukemia | Year: 2010

Elevated immunoglobulin free light chain (FLC) level and abnormal FLC ratio are commonly seen in multiple myeloma (MM) and have prognostic implications. We hypothesized that presence of immunoglobin heavy chain (IgH) translocations leads to unbalanced production of light chains and more extreme abnormalities of FLC, and may explain the prognostic value of FLC. We studied 314 patients with newly diagnosed MM enrolled in a phase III trial, in whom results of fluorescence in situ hybridization testing and data on serum FLC levels were available. Cytogenetic analyses and FLC estimates were performed on stored samples and results were correlated with clinical data. The median ratio (FLC ratio) and the absolute difference (FLC diff) between the involved and uninvolved FLC were higher among those with IgH translocations, especially t(14;16). In multivariate analysis, the prognostic value of FLC estimates on progression-free and overall survival were independent of high-risk IgH translocations t(4;14) and t(14;16). A combination of the risk factors; either abnormal FLC estimate and/or the presence of high-risk IgH translocation, achieved better prognostic stratification. We conclude that patients with IgH translocations have higher FLC levels and abnormal ratios, but the prognostic effect of FLC is only partially explained by translocation status. A system including both these risk factors allows better prediction of outcome. © 2010 Macmillan Publishers Limited All rights reserved. Source


Schneider B.P.,Eastern Cooperative Oncology Group | Zhao F.,ECOG | Wang M.,ECOG | Stearns V.,ECOG | And 9 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: Neuropathy is a common and potentially disabling complication of adjuvant taxane therapy. Recent studies have identified candidate single nucleotide polymorphisms associated with taxane-induced neuropathy. Therefore, we sought to determine whether neuropathy was associated with breast cancer recurrence in a clinical trial population who received adjuvant taxane therapy. Patients and Methods: Trial E1199 included 4,554 eligible women with operable breast cancer who received up to four cycles of doxorubicin and cyclophosphamide every 3 weeks followed by paclitaxel 175 mg/m 2 every 3 weeks for four cycles (P3), paclitaxel 80 mg/m 2 weekly for 12 cycles (P1), docetaxel 100 mg/m 2 every 3 weeks for four cycles (D3), or docetaxel 35 mg/m 2 weekly for 12 cycles (D1). A Cox proportional hazards model was used to determine the relationship between neuropathy and disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) by treating neuropathy status as a time dependent covariate and using a landmark analysis. Results: Of 4,554 patients who received at least one taxane dose, grade 2 to 4 neuropathy developed in 18%, 22%, 15%, and 13% of patients in the P3, P1, D3, and D1 arms, respectively. In a model that included age, race, obesity, menopausal status, tumor size, nodal status, treatment arm, neuropathy, and hyperglycemia, no significant relationship was found between neuropathy and DFS, OS, or RFS. Conclusion: There was no association between taxane-induced neuropathy and outcome. © 2012 by American Society of Clinical Oncology. Source

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