Cancer Research UK : Non-Hodgkin lymphoma symptoms and treatment

Non-Hodgkin lymphoma symptoms and treatment

This page presents information on Non-Hodgkin lymphoma (NHL) symptoms and treatment including radiotherapy, chemotherapy, monoclonal antibodies,immunotherapy, antimicrobials and new therapies.

The most common presenting symptom of non-Hodgkin lymphoma is painless enlargement of lymph nodes, which may occur at any site in the body, although the most frequent presentation is in the neck. The disease may involve a single, or multiple groups of lymph nodes.

Systemic symptoms are common, including unexplained fevers, drenching night sweats and weight loss – known as ‘B’ symptoms.

In addition to disease at nodal sites, 15-20% of NHL occur in lymphoid tissue elsewhere in the body. Extranodal lymphomas can occur at almost any anatomical site.

The gastro-intestinal system is the commonest primary extranodal site, although primary NHL of most other organs is well documented. Presenting symptoms may be related to extranodal disease, and may also be due to generalised metabolic complications of NHL, including hypercalcaemia (Table 6.1)

Table 6.1: Primary extranodal sites for NHL

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The treatment of NHL is undergoing rapid change, particularly with the introduction of specific therapies based upon monoclonal antibodies and small molecules. Notably, NHL is the first illness in which the use of a monoclonal antibody has been shown to improve survival, using the anti-CD20 reagent Rituximab in combination with chemotherapy.1

In the modern era several different modalities are used for patients with NHL who require treatment:

Radiotherapy treatment for NHL

A minority (10-15%) of patients with low grade lymphomas present with disease restricted to one lymph node group, and around 50% of these may be cured using involved field irradiation. Patients with aggressive NHL are treated where possible with combination chemotherapy, but for those with localised disease an abbreviated course of chemotherapy may be used in combination with local radiotherapy.

Radiotherapy is also used frequently for primary central nervous system lymphoma and for some patients with large masses at presentation.

Chemotherapy treatment for NHL

Single agent: Single alkylating agents (eg Chlorambucil) or purine analogues (eg Fludarabine) are widely used in the treatment of advanced low grade lymphoma, where it is generally accepted that no currently-available treatment is curative, and that the disease will pursue a relapsing and remitting course. (Although around 15% of patients in large series are found to survive long-term free of disease).

Combination: Combination chemotherapy such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) is the standard treatment in aggressive lymphoma. It also produces higher response rates and longer remissions but without comparably increased survival in low grade lymphoma, where it is generally reserved for treatment of recurrence. 2

High dose: Very intensive therapy with autologous stem cell transplantation has been shown to improve survival for patients with recurrent large cell lymphoma who are fit enough to undertake it. 3 It is also used successfully in the treatment of some patients with low grade disease and there is some data to suggest a survival benefit in recurrent follicular lymphoma. 4

Monoclonal antibody treatment for NHL

Monoclonal antibodies which target surface molecules on non-Hodgkin lymphoma cells are now a standard part of NHL therapy.

The antibody Rituximab, which recognises the CD20 B-cell marker, can be used alone for the treatment of low grade B-cell lymphoma or in combination with chemotherapy, particularly for aggressive types.5 An anti-CD20 antibody can also be conjugated to a radioisotope such as Iodine-131 or Yttrium-90 to deliver targeted irradiation.6

There are antibodies which can target T-cell lymphomas, and a recombinant protein comprising part Interleukin-2 and part diphtheria toxin (denileukin diftitox) is used for cutaneous T-cell lymphoma which expresses the CD25 interleukin-2 receptor.

Immunotherapy treatment for NHL

A variety of vaccines have been developed to provoke active immunity against lymphoma, many of them using the unique surface immunoglobulin sequences (the idiotype) as a tumour-specific target.7 These are the subject of ongoing clinical trials.

A less specific but more potent form of immunotherapy is the use of allotransplantation, in which donor stem cells are used to reconstitute the immune system after ablative therapy, giving rise to a graft-versus-lymphoma effect. The use of reduced intensity treatment regimens has made this a safer procedure recently, and for low grade NHL in particular the early results of clinical trials appear promising. 8

Antimicrobial therapy treatment for NHL

The identification of infectious agents as pathogenic in some types of lymphoma has led to testing of antimicrobial agents in their therapy.

In gastric MALT lymphoma the eradication of Helicobacter pylori has been shown to produce regression of the disease in a high proportion of cases9, and similar findings are emerging from the use of tetracycline in patients with orbital lymphoma.

The use of antiviral agents in EBV-related lymphoproliferative diseases is also showing promising results in clinical trials.

New therapies for NHL

Small molecule targeted therapy has also been tested in lymphoma. Agents such as the anti-angiogenic thalidomide, the proteosome inhibitor bortezomib, the inhibitors of the mammalian target of rapamycin and of histone deacetylases have all entered clinical trials with interesting responses being seen. 10

The incidence of NHL is increasing which is partly due to increases in immunodeficiency, auto-immunity and viral infections. In most cases the causes of NHL are still not understood.

There have been some important advances in understanding the development of healthy lymphocytes and the pathogenesis of NHL, yielding significant improvements in the use of specifically targeted therapy. In many cases of NHL treatment results in cure, and the proportion of these is rising.

References for non-Hodgkin lymphoma symptoms and treatment

Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346(4):235-42.
A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 1993;329(14):987-94.
Johnson PW, Rohatiner AZ, Whelan JS, et al. Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center. J Clin Oncol 1995;13(1):140-7.
Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 1995;333(23):1540-5.
Schouten HC, Qian W, Kvaloy S, et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol 2003;21(21):3918-27.
Kaminski MS, Estes J, Zasadny KR, et al. Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood 2000;96(4):1259-66.
Stevenson FK, Zhu D, King CA, Ashworth LJ, Kumar S, Hawkins RE. Idiotypic DNA vaccines against B-cell lymphoma. Immunol Rev 1995;145:211-28. Blood 2000;96(4):1259-66.
Morris E, Thomson K, Craddock C, et al. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood 2004;104(13):3865-71.
Neubauer A, Thiede C, Morgner A, et al. Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst 1997;89(18):1350-5.
Goy A, Younes A, McLaughlin P, et al. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol 2005;23(4):667-75.

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