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mon cancer in Australia , with over 7000 cases diagnosed each year . 1 The therapeutic landscape has substantially evolved with an improved understanding of the pathophysiology of the disease . Though chemotherapy remains a cornerstone of treatment in most patients , newer therapeutic approaches including oral targeted therapies , monoclonal antibodies and immunotherapies are assuming increasing importance .

This How to Treat summarises recent developments in the treatment of lymphoma , focusing on the mechanisms and toxicities of these novel therapies and the practical management of patients in the community .

BIOLOGY OF

LYMPHOPOIESIS

LYMPHOCYTES are the main mediators of the adaptive immune system ( see figure 1 ). They provide a rapid and sustained defence against pathogens , particularly those that the body has previously encountered . 2 The two main types are B and T lymphocytes .

B lymphocytes mature in the bone

‘ secondary lymphoid organs ’ ( lymph nodes and spleen ). They recognise antigens through contact with the B-cell receptor , which leads to a cascade of signalling that results in B-cell activation and proliferation . Some B-cells mature into plasma cells and secrete immunoglobulins , which can bind pathogens and lead to direct toxicity as well as facilitate cell mediated death . Other B-cells become memory cells , providing the immunological memory that allows the rapidity of response to infections and is the biological basis of immunisation . 3

T lymphocytes are crucial in the co-ordination of the immune response and control of intracellular pathogens . They are divided into several functional subsets , with the two most important being the helper and cytotoxic T-cells . T helper cells ( CD4 positive ) recognise antigens that are presented to them by specialised antigen presenting cells , leading to signalling through the T-cell receptor and the release of numerous cytokines and activation of other cells including B lymphocytes . Cytotoxic T-cells ( CD8 positive ) can recognise and destroy cells that have been infected with intracellular

A key strength of the adaptive immune system is its ability to recognise a vast number of potential antigens . However , the genetic program that leads to this diverse repertoire of cell surface receptors is also prone to error , leading to abnormal proliferation of lymphocyte clones . 5

Natural killer cells , a third type of lymphocyte , trigger cytokine release and directly kill virus infected and tumour cells ; natural killer cells form part of the innate immune response .

While the aetiology of most lymphomas is unknown , several risk factors , such as immunosuppressed states ( for example , following solid organ transplantation , or HIV infection ), and Epstein-Barr virus are implicated in a variety of lymphoma subtypes .

DIAGNOSIS

THE WHO has more than 50 different subtypes of lymphoma categorised in their classification of lymphoid neoplasms . 6 An accurate diagnosis ( see box 1 ), based on adequate tissue , is vital for determining the choice of therapy , given the substantial variation in natural history and management . The latter is particularly

used for specific lymphoma subtypes . A core biopsy of lymph node ( see figure 2 ) or tissue is usually the minimum required for diagnosis , though an excision biopsy may be preferred if a suspicious lymph node is easily accessible . Fine needle aspiration biopsy has the potential to result in inadequate diagnostic information .

CLASSIFICATION

THE first broad division in classification is between Hodgkin ’ s lymphoma and non-Hodgkin ’ s lymphoma .

Hodgkin ’ s lymphoma comprises about 10 % of cases of lymphoma , and most commonly presents in younger adults . 7 Patients in the early stage often present with isolated lymphadenopathy involving the cervical and axillary lymph nodes with or without involvement of the mediastinum ; advanced cases affect lymph nodes and organs above and below the diaphragm . The histopathology of Hodgkin ’ s lymphoma is characterised by the presence of the neoplastic Reed-Sternberg cell within a dense inflammatory infiltrate . 7

Non-Hodgkin ’ s lymphoma has numerous subtypes based on

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marrow and circulate in the blood and

pathogens such as viruses . 4

important as new therapies may be

the origin and stage of

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