Non-Hodgkin's Lymphomas (NHL)



  • Lymphomas are cancers that develop in the lymphatic system, which is part of the body's immune system.
  • Lymphomas are divided into two general types: Hodgkin's lymphomas and non-Hodgkin's lymphomas.
  • Non-Hodgkin’s lymphomas are a large, diverse group of lymphomas that do not have the typical appearance of Hodgkin’s disease under the microscope.
  • Traditionally, Non-Hodgkin’s lymphomas have been divided into two large groups: Low Grade Lymphomas and High Grade Lymphomas.


Lymphomas are cancers that develop in the lymphatic system, part of the body's immune system. Lymphomas are divided into two general types: Hodgkin's disease and non-Hodgkin's lymphomas.

Non-Hodgkin’s lymphomas are a large diverse group of lymphomas that do not have the typical appearance of Hodgkin’s disease under the microscope. These lymphomas vary considerably in their appearance under a microscope.

This large group of lymphomas includes some very aggressive variants, and others that are much less aggressive (indolent).

Generally, Non-Hodgkin’s lymphomas have in the past been divided into two big groups depending on their clinical behaviour:

  • Low Grade Lymphomas: They have an indolent course, frequently involve multiple lymph node groups, bone marrow and other organs and though they are not very aggressive (in the sense that they develop slowly), these types of lymphomas are rarely curable.
  • High Grade Lymphomas: Very aggressive cancers with a rapid clinical course. If left untreated they will cause the death of the patient within a few months. However, high-grade lymphomas are potentially curable with modern combined methods of treatment.


Non-Hodgkin’s lymphoma occurs five times more often than Hodgkin’s disease. It can be found in children and adults. Usually the low grade lymphomas occur in adults and not children. There has been a yearly increase of between 3-4% in the incidence of non-Hodgkin’s lymphoma. This may be due to the fact that it is one of the malignancies found in patients with Aids. These lymphomas are also found in patients that are immune-suppressed for other reasons, such as after a renal transplant. However, there is still a high incidence of this disease in patients without any form of immunodeficiency.


The symptoms of the disease depend on the specific type of lymphoma, but generally are the same as the symptoms of Hodgkin’s disease:

  • Painless swelling of the lymph nodes in the neck, underarm, or groin
  • Fever
  • Night sweats
  • Tiredness
  • Weight loss without dieting
  • Itchy skin


The diagnosis of non-Hodgkin’s lymphoma is made by examining a lymph node after it has been removed by a surgeon (the procedure called a lymph node biopsy) under a microscope. Usually several additional immunological tests are needed to confirm the specific subtype of lymphoma that is present.


As with Hodgkin’s lymphoma, several additional blood tests, X-rays and CT scans are necessary to stage the lymphoma before treatment can be started. The stage of the disease is based on the extent of the disease in each particular patient’s body (this is discussed in the article on Hodgkin’s disease).

Stage I: A single lymph node region

Stage II:I nvolvement of two or more lymph node regions on the same side of the diaphragm

Stage III: Involvement of lymph node regions on both sides of the diaphragm

Stage IV: Disseminated involvement of one or more extralymphatic regions such as the bone marrow


There are treatments for all patients with adult non-Hodgkin's lymphoma. Four types of treatment are used:

  • Radiation therapy
  • Chemotherapy
  • Biological therapy (using the body's immune system to fight cancer)
  • Bone marrow transplantation

Please see the brief explanation of radiation therapy, chemotherapy and bone marrow transplantation in the discussion for Hodgkin’s Disease.

Biological treatment tries to help the body to fight cancer or infections. It uses materials made by the body or made in a laboratory to boost, direct or restore the body's natural defences against disease. Biological treatment is sometimes called biological response modifier (BRM) therapy.

Treatment by stage

Treatment of adult non-Hodgkin's lymphoma depends on:

  • The stage of the disease
  • The histology and the grade of the disease
  • The patient's age and general health

Standard treatment may be considered, based on its effectiveness in patients in past studies, or participation in a clinical trial. Not all patients are cured with standard therapy, and some standard treatments may have more side effects than desired. For these reasons, clinical trials are designed to find better ways to treat cancer patients and are based on the most up-to-date information.

Treatment of low grade NHL: Most of these tumours present in advanced stage III and Stage IV of the disease. In very rare cases when the tumour is discovered in Stage I or II (enlargement of only one or two groups of lymph nodes on the same side of the diaphragm), low grade NHL is potentially curable with a course of radiotherapy as a single modality of treatment. In some cases even watchful waiting could be a reasonable alternative, especially in older patients with many other medical problems and who do not show symptoms of rapid progression.

It is not unusual to find the disease recurs in these patients, with enlargement of other groups of lymph nodes outside the radiotherapy field, or in the bone marrow months or years later. This shows that the lymphoma had spread far more widely than was initially thought. This is the reason why most of the current treatment protocols include a course of chemotherapy relatively early in the treatment of NHL.

The chemotherapy is given as tablets or as intravenous infusion. It works throughout the whole body, reaching cells that would otherwise remain outside the location where the radiotherapy is directed.

The treatment of Stage III (lymph nodes affected on both sides of the diaphragm) and Stage IV (bone marrow or other organs also involved) is primarily chemotherapy.

Chemotherapy, however, will probably never cure low grade NHL. It merely puts it in remission, which could last for many years. Doctors divide remission into types:

  • Clinical remission: no enlarged lymph nodes can be found on examination and on X-ray.
  • Pathological remission: there is no sign of the disease, even in biopsies from lymph nodes and bone marrow.

Depending on the completeness of the response, remissions could be classified as:

  • Complete remission (complete response): no evidence of the lymphoma whatsoever
  • Partial remission (partial response): the enlarged lymph nodes are still present, but they are much smaller and do not enlarge further if they are left without treatment.

Bone marrow transplantation from a compatible brother and sister (allogeneic transplant) could also be used where a cure is aimed for.

In a relatively new treatment of recurrent disease (immunotherapy), biological substances called antibodies are directed to the tumour cell molecules. Though the initial response can be fantastic, a long-lasting complete response (over 2 years) is very rare.

Treatment options for indolent recurrent adult non-Hodgkin's lymphoma:
Indolent lymphomas often come back (relapse) after they have been treated. Sometimes in about 5 to 10% of patients, the lymphoma will come back as a different cell type (histology), most commonly as an aggressive lymphoma. If this is the case (called transformation of the lymphoma), see the treatment section for aggressive, recurrent non-Hodgkin's lymphoma.

If the lymphoma comes back and it is still a low-grade lymphoma, treatment may be one of the following:

Treatment options for high-grade NHL:

Though the lymphomas from this group are very aggressive, rapidly developing tumours, they are also sensitive to chemotherapy and radiotherapy. They frequently involve certain groups of lymph nodes (in contrast with the widespread low grade NHL) and are potentially curable. “Cure” is the aim in treatment, not just “remission”.

Treatment options available for Stage I, II:

  • Chemotherapy plus radiation therapy
  • Chemotherapy alone
  • Radiation therapy alone if the patient is too frail to receive any chemotherapy

Treatment options for high grade Stage III, and IV NHL:

Treatment may be one of the following:

  • Combination chemotherapy
  • Bone marrow transplantation( peripheral stem cell transplantation) for patients with high risk disease (high IPI score) in first remission and for all patients who are fit enough and who are younger than 65 years of age who relapse after initially obtaining a complete remission state and can be returned to second remission with combination chemotherapy
  • Clinical trials are evaluating new combination chemotherapies.

Treatment options for adult lymphoblastic lymphoma:

This is a very aggressive form of adult non-Hodgkin's lymphoma. Treatment is for this reason usually based on acute lymphocytic leukaemia protocols (very aggressive high-dose chemotherapy regimens). Treatment consists of the following:

  • Combination chemotherapy including treatment of the central nervous system with or without radiation therapy
  • Radiation therapy
  • Bone marrow (peripheral stem cell) transplantation in first remission if it can be achieved and patient is fit enough to undergo the procedure.

Treatment options for recurrent aggressive non-Hodgkin's lymphoma:

Treatment may be one of the following:

  • Bone marrow(peripheral stem cell) transplantation
  • Bone marrow (peripheral stem cell) transplantation plus radiation therapy
  • A clinical trial of chemotherapy, bone marrow transplantation or peripheral stem cell transplantation and radiation therapy
  • A clinical trial of immunotherapy

Previously reviewed by Dr Adrian Schmidt, MBChB (Pretoria) ,M Med Internal Medicine (Stellenbosch)

Reviewed by Dr David Eedes, Oncologist, March 2011

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