Evaluation of prognostic values of clinical and histopathologic characteristics in diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy

Departments of Internal Medicine, Gachon University Gil Hospital, Gachon University of Medicine and Science School of Medicine, Incheon, Korea.
Leukemia & lymphoma (Impact Factor: 2.89). 06/2011; 52(10):1904-12. DOI: 10.3109/10428194.2011.588761
Source: PubMed


The relationship between histopathologic characteristics and treatment outcomes in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-based immunochemotherapy needs re-evaluation. Patients with newly diagnosed DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were evaluated with respect to clinical characteristics, treatment efficacy, and survival. Immunohistochemistry of bcl-2, CD10, bcl-6, and MUM-1 was performed and patients were sub-classified as germinal center B-cell-like (GCB) or non-GCB type according to the Hans algorithm. There was no significant difference in overall survival (OS) between patients with GCB and those with non-GCB. Although there was no significant difference in OS between high-intermediate and high risk groups as classified by the standard International Prognostic Index (IPI; p = 0.50), all three groups with the revised IPI had a clear-cut separation for event-free survival and OS. The revised IPI better predicted survival than did the standard IPI in patients with DLBCL treated with R-CHOP. The Hans classification had no prognostic value.

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    • "Diffuse large B-cell lymphoma (DLBCL) represents 30–40% of newly diagnosed adult Non-Hodgkin lymphomas (NHL), and is a heterogeneous group of disorders with variable histological and clinical behaviour (The Non-Hodgkin's Lymphoma Classification Project's, 1997; De Paepe & De Wolf-Peeters, 2007; Jaffe, 2009; Flowers et al, 2010; Nogai et al, 2011; Shenoy et al, 2011). Strong prognostic indicators of outcomes include the International Prognostic Index (IPI) and molecular and genomic markers (Rosenwald et al, 2002; Shipp et al, 2002; Gascoyne et al, 2010; Hong et al, 2011). "
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) occasionally presents with circulating malignant cells. The clinical characteristics and long-term outcomes of these patients have not been described. Twenty-nine newly diagnosed DLBCL presenting in leukaemic phase were identified between 1996 and 2010, at two institutions. Median age was 48 years, and patients presented with leucocytosis, high lactate dehydrogenase levels, B symptoms, and high International Prognostic Index score. Extra nodal site involvement was observed in all patients and affected the bone marrow (100%), spleen (62%), pleura/lung (41%), liver (21%), bone (17%), bowels (7%) and cerebrospinal fluid (14%). Blood lymphomatous cells co-expressed CD19, CD20, CD22, CD38, CD45, HLA-DR and FMC7 in >90%, and kappa or lambda light chain restriction in >50%. Ninety per cent received rituximab and anthracycline-based chemotherapy. Overall, remission was complete in 54% and partial in 31%; 15% had resistant disease. Median follow-up was 47 months; 13 (45%) patients remain alive in complete remission. Median progression-free and overall survivals were 11·5 and 46·7 months, respectively. In summary, patients with DLBCL in leukaemic phase present with high tumour burden and frequent involvement of extra nodal sites. In this uncommon DLBCL subgroup, anthracycline-based regimens with rituximab are associated with early morbidity and mortality, but yield approximately 50% 4-year survival.
    Full-text · Article · Jul 2012 · British Journal of Haematology
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    ABSTRACT: Although patients with B-cell non-Hodgkin's lymphoma (NHL) usually respond to initial conventional chemotherapy, they often relapse and mortality has continued to increase over the last three decades in spite of salvage therapy or high dose therapy and stem cell transplantation. Outcomes vary by subtype, but there continues to be a need for novel options that can help overcome chemotherapy resistance, offer new options as consolidation or maintenance therapy postinduction, and offer potentially less toxic combinations, especially in the elderly population. The bulk of these emerging novel agents for cancer treatment target important biological cellular processes. Bortezomib is the first in the class of proteasome inhibitors (PIs), which target the critical process of intracellular protein degradation or recycling and editing through the proteasome. Bortezomib is approved for the treatment of relapsed or refractory mantle cell lymphoma. The mechanisms of proteasome inhibition are very complex by nature (because they affect many pathways) and not fully understood. However, mechanisms of action shared by bortezomib and investigational PIs such as carfilzomib, marizomib, ONX-0912, and MLN9708 are distinct from those of other NHL treatments, making them attractive options for combination therapy. Preclinical evidence suggests that the PIs have additive and/or synergistic activity with a large number of agents both in vitro and in vivo, from cytotoxics to new biologicals, supporting a growing number of combination studies currently underway in NHL patients, as reviewed in this article. The results of these studies will help our understanding about how to best integrate proteasome inhibition in the management of NHL and continue to improve patient outcomes.
    Preview · Article · May 2012 · The Oncologist
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    ABSTRACT: In order to evaluate prognostic value of CD99 expression in patients with diffuse large B-cell lymphoma (DLBCL) who underwent treatment with rituximab-CHOP immunochemotherapy, immunohistochemistry for CD99/CD10/BCL-2/BCL-6/MUM-1 was performed on nodal DLBCL specimens from 70 patients. Patients were classified as either germinal center B-cell (GCB) subtype or non-GCB subtype according to the Muris algorithm. A superior 2-year event-free survival (EFS) was observed in patients with the GCB subgroup, compared to those with the non-GCB subgroup (p = 0.034). The distribution of CD99 expression (29 patients; 41.4 %) did not show deviation according to subtype and was not prognostic for survival in the entire patient population. Among patients with the GCB subgroup, better EFS and overall survival (OS) were observed in CD99+ patients, compared to CD99- patients. Conversely, among patients with the non-GCB subgroup, inferior EFS and OS were reported in CD99+ patients. Superior 2-year EFS (p = 0.004) and 2-year OS (p = 0.003) were observed in patients with GCB/CD99+ and non-GCB/CD99- compared to the others, and the combination classification was found to be an independent prognostic factor.
    Full-text · Article · Aug 2012 · Annals of Hematology
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