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INTRODUCTION

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According to last year’s published cancer statistics, approximately 54,370 new cases were diagnosed and 19,410 patients died from lymphoma despite currently available treatment [1]. Non-Hodgkin’s lymphomas (NHL) are the fifth most common cancer in the United States and the sixth most common cause of cancer-related death in the United States [1].

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Recent advances in immunology, genetics, and molecular biology have provided a large and diverse body of information that has changed the management of patients with human immunodeficiency virus (HIV) infection, leukaemia and lymphoma [2–7]. Increasing use of laboratory tools such as polymerase chain reaction (PCR) amplification of DNA/RNA, Southern blotting, and fluorescent in situ hybridisation for chromosomal analysis has led to a better understanding not only of the biological process of lymphoid maturation, but also the pathophysiology of NHL.

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NHL is a heterogeneous group of malignancies with diverse biology, clinical behaviour, and prognosis. In the past, treatment modalities depended primarily on the histological type/stage of NHL and ranged from watchful waiting, radiotherapy, single-agent chemotherapy, combination chemotherapy, and high-dose chemotherapy with autologous or allogeneic stem cell rescue.

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The development of target-specific therapies such as monoclonal antibodies (mAbs i.e. rituximab) has emerged in response to the need to develop novel treatments with increased efficacy and decreased toxicity than that associated with existing treatment regimens.

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Rituximab has been evaluated worldwide in multiple clinical trials as a single agent or in combination with systemic chemotherapy in patients with various subtypes of B-cell neoplasms. The information obtained from these clinical trials has significantly changed the treatment paradigm for, and the outcome of, patients with B-cell lymphomas. In this chapter we present an overview of the evolution of rituximab-based therapies for B-cell NHL and how the incorporation of rituximab into chemotherapy regimens has resulted in an improvement in time-to-progression (TTP) and overall survival (OS) in various subtypes of B-cell lymphoma.

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RITUXIMAB

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The concept of using mAbs to treat lymphoma was initially tested in the early 1980s when two independent groups of investigators reported the first cases of lymphoma patients responding to a mouse anti-idiotype antibody [8–9]. However, subsequent early clinical studies were disappointing. Several factors contributed to poor outcomes: (1) suboptimal antigen selection (i.e. modulation of the antibody-antigen complex or antigen shedding), (2) rapid clearance of antibody, and (3) development of xenograft immune reaction to the mAb (production of human anti-mouse antibodies by the host) [10–11]. Advances in molecular biotechnology and tumour immunology lead to the development of chimeric or humanised mAbs with increased biological anti-tumour activity, longer half-lives, and decreased immunogenicity. Results from recent clinical trials have confirmed the improved anti-tumour activity of these newer mAbs, particularly rituximab [12–14].

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Rituximab is an IgGκ chimeric mAb directed against the CD20 antigen expressed on normal B cells and the majority of B-cell NHL [...

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