Diagnosis of non-Hodgkin’s lymphoma

Specific subtypes of NHL

Diffuse large B-cell lymphoma
This aggressive subtype (Figure 2) is the most common subtype of NHL and accounts for 30% to 40% of cases. Early stage disease is usually treated with short-course chemotherapy followed by involved field radiotherapy. For many years the conventional treatment of advanced stage disease was CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) on a three-weekly basis. It has been found that the addition of the monoclonal antibody rituximab (R-CHOP chemotherapy) improves response rates, progression-free survival and overall survival. R-CHOP is now the standard treatment and has been endorsed by NICE.³

Current studies are investigating increasing treatment intensity by shortening the interval between cycles from 21 to 14 days. In the case of relapsed disease, for patients who are fit enough, the standard treatment is high-dose chemotherapy with autologous stem cell rescue.

Follicular lymphoma
This is the second most common subtype and the most common low-grade lymphoma (Figure 3). It is named according to the follicular pattern seen histologically.

A watch and wait approach remains the standard for patients with asymptomatic disease at presentation. For those requiring treatment, the first-line approach in the UK is rituximab plus cyclophosphamide, vincristine, and prednisolone (R-CVP).⁴ This follows a NICE recommendation that rituximab is given with the other three drugs as treatment for patients with symptomatic stage III or IV follicular lymphoma who have not been treated before.⁵

There is a wide range of treatments for relapsed disease, although NICE has approved the use of rituximab alongside chemotherapy to induce remission and as a maintenance therapy in this setting.

Autologous transplantation can be used in relapsed disease, but is not usually curative and will increase the risk of second malignancies. The use of reduced intensity allogeneic transplant is on the increase, especially in younger patients. Newer treatment options include radio-immunotherapy (such as ibritumomab) and new monoclonal antibodies. Follicular lymphoma may undergo transformation to a high-grade lymphoma and this is associated with a poor outlook.

Burkitt’s lymphoma
This is a highly aggressive lymphoma that often presents at extranodal sites or as an acute leukaemia. The three main subtypes are endemic Burkitt’s lymphoma, which occurs in sub-Saharan Africa and is associated with Epstein-Barr virus; sporadic Burkitt’s lymphoma, which occurs worldwide, mainly in children and young adults; and immunocompromised associated Burkitt’s lymphoma, which is primarily seen in HIV.

The treatment for Burkitt’s lymphoma consists of multiagent chemotherapy including high-dose methotrexate and intrathecal chemotherapy injections to target the CNS. Approximately two-thirds of patients with the condition will be cured with this treatment.

Mantle cell lymphoma
Mantle cell lymphoma accounts for 3% to 10% of NHL occurring in middle and older age and usually presents with advanced stage disease. Although it usually responds to initial chemotherapy, it is generally considered incurable and is associated with a poor prognosis. The standard treatment is CHOP chemotherapy followed by autologous transplantation.

Marginal zone lymphoma
Marginal zone lymphomas are typically extranodal and usually localised. This group includes mucosal-associated lymphoid tissue (MALT) lymphomas. These are associated with infectious agents. Gastric MALT is the most common form and is associated with Helicobacter pylori infection. Many patients will respond to antibiotic therapy to eliminate H pylori. Overall, this subtype is associated with long-term survival.

AIDS-related lymphoma
The incidence of NHL in HIV-infected individuals is approximately 100 times the incidence among the general population. The second most common cancer in HIV, it usually occurs as a late event in HIV associated with low CD4 counts, high viral load and increasing age. The incidence is decreasing since the introduction of highly active antiretroviral therapy.

Autoimmune cytopaenias
The incidence of autoimmune cytopaenias, especially autoimmune haemolytic anaemia and immune thrombocytopenic purpura, is increased in NHL. They are seen mainly in low-grade disease.

Dr Emma Welch is a specialist registrar in haematology and Dr Nicholas Morley is consultant haematologist, Department of Haematology, Royal Hallamshire Hospital, Sheffield. Competing interests: None declared.

References
1. Cancer Research UK. UK Non-Hodgkin lymphoma incidence statistics (accessed 27 July 2009).
2. Jaffe ES, Harris NL, Stein H et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissue. Lyon, IARC Press, 2001.
3. NICE. Guidance on rituximab for aggressive non Hodgkin’s lymphoma. TA65. London, NICE, 2003. (accessed 27 July 2009).
4. NICE. Guidance on rituximab for the treatment of follicular lymphoma. TA110. London, NICE, 2006. (accessed 31 July 2009).
5. NICE. Guidance on the use of rituximab for recurrent or refractory stage III or IV follicular non-Hodgkin’s lymphoma. TA37. London, NICE, 2008. (accessed 27 July 2009).

1. Cancer Research UK. UK (accessed 27 July 2009).2. Jaffe ES, Harris NL, Stein H . . Lyon, IARC Press, 2001.3. NICE. Guidance on rituximab for aggressive non Hodgkin’s lymphoma. . London, NICE, 2003. (accessed 27 July 2009).4. NICE. Guidance on rituximab for the treatment of follicular lymphoma. . London, NICE, 2006. (accessed 31 July 2009).5. NICE. Guidance on the use of rituximab for recurrent or refractory stage III or IV follicular non-Hodgkin’s lymphoma. . London, NICE, 2008. (accessed 27 July 2009).

Originally published in the September 2009 edition of MIMS Oncology & Palliative Care.