This report by an international consensus panel updates current recommendations for defining clinical response in Waldenstrom's macroglobulinemia (WM). The previously published response criteria incorporated parameters for monoclonal protein reduction and/or improvement of marrow and nodal involvement, and included definitions of complete and partial remissions. The criteria have been updated to include minor response and stable disease categories. In addition, the criteria now recognize that delayed responses after treatment with nucleoside analogues and biologic agents and the time point for assessing response in patients with WM should be considered so as to not miss or miscategorize a response. The new criteria should therefore help in better delineating responses to therapy in patients with WM, particularly with the wide use of nucleoside analogues and biologically based agents for this disease.
"In case of Leukemia, more than 70% of the cluster is functionally associated in half of the enriched attributes. Waldenstroms macroglobulinemia (WM) is a C-cell monoclonal disorder that is characterized by infiltration of lymphoplasmacytic cells to bone marrow along with excessive presence of IgM in blood . It is suggested that genetic factor plays significant role in pathogenesis of the cancer . "
[Show abstract][Hide abstract] ABSTRACT: Various statistical and machine learning based algorithms have been proposed in literature for selecting an informative subset of genes from microarray data sets. The recent trend is to use functional knowledge to aid the gene selection process. In this paper we propose a clustering algorithm which generates multiple views (clusters) from the microarray expression profiles, each representing a particular facet of the data. Such multiple clusters are found to represent strongly connected regions of the known protein–protein interaction (PPI) networks, perhaps corresponding to those responsible for certain biological processes. Thus we integrate microarray data clustering with PPI knowledge to obtain enriched gene sets. Results on benchmark microarray data sets demonstrate the competitiveness of our method compared to gene selection techniques.
IEEE International Conference on BioInformatics and BioEngineering, Boca Raton; 11/2014
"Despite the routine recommendation for M-Rituximab in all WM patients since 2001, its use was subject to patient tolerance to rituximab during induction, parameters set forth in clinical trials that individual patients elected to participate, and insurance approval. Response determinations were made using modified consensus panel criteria from the Third International Workshop on WM (Kimby et al, 2006; Treon et al, 2009a,b). A complete response (CR) was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly . "
[Show abstract][Hide abstract] ABSTRACT: This study examined the outcome of 248 Waldenstrom macroglobulinaemia (WM) rituximab-naïve patients who responded to a rituximab-containing regimen. Eighty-six patients (35%) subsequently received maintenance rituximab (M-Rituximab). No differences in baseline characteristics, and post-induction categorical responses between cohorts were observed. The median rituximab infusions during induction was 6 for both cohorts; and 8 over a 2-year period for patients receiving M-Rituximab. Categorical responses improved in 16/162 (10%) of observed, and 36/86 (41·8%) of M-Rituximab patients respectively, following induction therapy (P < 0·0001). Both progression-free (56·3 vs. 28·6 months; P = 0·0001) and overall survival (Not reached versus 116 months; P = 0·0095) were longer in patients who received M-Rituximab. Improved progression-free survival was evident despite previous treatment status, induction with rituximab alone or in combination therapy (P ≤ 0·0001). Best serum IgM response was lower (P < 0·0001), and haematocrit higher (P = 0·001) for patients receiving M-Rituximab. Among patients receiving M-Rituximab, an increased number of infectious events were observed, but were mainly ≤ grade 2 (P = 0·008). The findings of this observational study suggest improved clinical outcomes following M-Rituximab in WM patients who respond to induction with a rituximab-containing regimen. Prospective studies aimed at clarifying the role of M-Rituximab therapy in WM patients are needed to confirm these findings.
British Journal of Haematology 05/2011; 154(3):357-62. DOI:10.1111/j.1365-2141.2011.08750.x · 4.71 Impact Factor
"The study was approved by the Dana Farber Cancer Institute/Harvard Cancer Center Institutional Review Board. Response determinations were made using modified consensus criteria, and response rates determined on an intent-to-treat basis (Kimby et al, 2006; Treon et al, 2009a,b). A CR was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation , a bone marrow biopsy demonstrating no evidence of disease, and resolution of any adenopathy or splenomegaly. "
[Show abstract][Hide abstract] ABSTRACT: The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom macroglobulinaemia (WM), though the impact of achieving better responses remains to be determined. We examined response depth on progression-free survival (PFS) in 159 rituximab-naïve WM patients who received rituximab-based therapy. The median follow-up was 33·5 months, and categorical responses were as follows: complete response (CR, 8·8%); very good partial response (VGPR, 13·2%); partial response (50%); minor response (18·9%); Non-Responders (8·8%). Sequencing for polymorphic variants of FCGR2A, FCGR2B, and FCGR3A was performed, and impact on response depth determined. Achievement of better categorical responses was incrementally associated with improved PFS (P < 0·0001). No separation was observed between CR and VGPR, and attainment of at least a VGPR was associated with improved time-to-progression. Neither age, serum IgM, haematocrit, platelet count, serum β(2) microglobulin, WM International Prognostic Scoring System score, and treatment group predicted for CR/VGPR. Polymorphisms at FCGR3A-48 and -158 were associated with improved categorical responses, particularly attainment of CR/VGPR (P ≤ 0·03). The attainment of CR/VGPR was associated with significantly longer PFS in rituximab-naïve WM patients undergoing rituximab-based therapy, and was predicted by polymorphisms in FCGR3A.
British Journal of Haematology 05/2011; 154(2):223-8. DOI:10.1111/j.1365-2141.2011.08726.x · 4.71 Impact Factor
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