Pathophysiology and molecular aspects of diffuse large B-cell lymphoma.

2012

Gouveia GR, Siqueira SA, Pereira J.

Source

Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo - USP, São Paulo, SP, Brazil.

Abstract

Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkinlymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multifactorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6, and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma.

PubMed

Prognostic significance of rituximab and radiotherapy for patients with primary mediastinal large B-cell lymphoma receiving doxorubicin-containing chemotherapy.

Nov 2012

Xu LM, Fang H, Wang WH, Jin J, Wang SL, Liu YP, Song YW, Ren H, Zhou LQ, Li YX.

Abstract

The aim of this study was to evaluate the prognostic importance of rituximab and radiotherapy in patients with primary mediastinal large B-cell lymphoma (PMBCL) receiving doxorubicin-containing chemotherapy. Seventy-nine patients with PMBCL received CHOP chemotherapy with (n = 39) or without rituximab (n = 40), and 60 patients received additional radiotherapy. Patients treated with R-CHOP had significantly superior survival rates. The 5-year overall survival (OS) and progression-free (PFS) rates were 83.7% and 76.7% for R-CHOP, compared with 48.3% (P=0.011) and 44.2% (P=0.012) for CHOP, respectively. Similarly, the 5-year OS and PFS rates for early stage patients were 93.8% and 84.6% with R-CHOP, and 52.0% (P=0.002) and 46.6% (P=0.003) with CHOP, respectively. Patients treated with chemotherapy and radiotherapy had better survival and local control (LC) rates compared with chemotherapy alone. The 5-year OS, PFS and LC rates for early stage patients were 73.6%, 69.9% and 92.6% for chemotherapy and radiotherapy, and 50.8% (P = 0.076), 36.9% (P = 0.008) and 56.4% (P<0.001) for chemotherapy alone, respectively. Early stage patients treated with R-CHOP and radiotherapy had 5-year OS, PFS and LC rates of 96.4%, 85.9% and 93.1%. R-CHOP plus consolidation radiotherapy was associated with excellent survival and LC rates.

PubMed