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Non-Hodgkin's lymphomas (NHLs) are a very diverse (heterogeneous) group of cancers of the lymph system with  differing patterns of behavior and responses to treatment. The lymph system is made up of thin tubes that branch, like blood vessels, into all parts of the body. Lymph vessels carry lymph, a colourless, watery fluid that contains white blood cells called lymphocytes. Along the network of vessels are groups of small, bean-shaped organs called lymph nodes. Clusters of lymph nodes are found in the underarm, pelvis, neck, and abdomen. The lymph nodes make and store infection-fighting cells. The spleen (an organ in the upper abdomen that makes lymphocytes and filters old blood cells from the blood), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat) are also part of the lymph system.

Because lymph tissue is found in many parts of the body, non-Hodgkin's lymphoma can start in almost any part of the body. The cancer can spread to almost any organ or tissue in the body, including the liver, bone marrow (the spongy tissue inside the large bones of the body that makes blood cells), spleen, and nose.  Unlike Hodgkin's lymphoma  NHL is much less predictable and far more likely to spread outside the lymphatic system to other sites or major organs. Tumours that occur outside a lymph node are often referred to as extranodal tumours. 

The NHLs can be divided into 2 prognostic groups: the indolent lymphomas and the aggressive lymphomas. Indolent NHL types have a relatively good prognosis, with median survival as long as 10 years, but they usually are not curable. Early-stage (I and II) indolent NHL can be effectively treated with radiation therapy alone, and sometimes this will result in a cure for those patients. Unfortunately due to the lack of symptoms, indolent lymphomas are rarely diagnosed in early stages and the majority of patients present at stage III or IV. Unlike most other cancers the stage is less of a prognostic factor, and those with stage IV disease have about as good a prognosis as those with stage III or II.  Follicular is the most common of the indolent types of lymphoma and comprises about 70% of all indolent lymphomas. Follicular just means the malignant cells tend to clump together. 

The aggressive type of NHL has a shorter natural history, but a significant number of these patients can be cured with intensive combination chemotherapy regimens. In general, with modern treatment of patients with NHL, overall survival at 5 years is approximately 50% to 60%. Thirty percent to 60% of patients with aggressive NHL can be cured. The vast majority of relapses occur in the first 2 years after therapy. The risk of late relapse is higher in patients with both indolent and aggressive disease. This is often a result of a transformation from indolent to aggressive. Transformation rarely involves 100% of the malignant cells, so when the transformation occurs the patient has both types of NHL. See the "Treatment Outcomes" page for the International Prognostic Index which measures the risk of relapse for patients with aggressive lymphoma. The most common type of aggressive lymphoma is Diffuse Large B-cell lymphoma. This accounts for approximately 30% of all lymphomas combined. 

While indolent NHL is responsive to radiation therapy and chemotherapy, a continuous rate of relapse is usually seen in advanced stages. However, patients can often be retreated with considerable success as long as the disease remains low grade. Patients who are diagnosed with, or convert to aggressive forms of NHL may have sustained complete remissions with combination chemotherapy regimens. Often high dose chemotherapy with a Stem Cell Transplant is used, especially for those with aggressive NHL who relapse after their initial chemotherapy. Stem Cell Transplants (SCT)  have largely replaced Bone Marrow Transplants as the treatment of choice because they offer a more rapid recovery, and lower risk of death. The primary difference between the two methods is that in an SCT the stem cells are collected from the circulating blood by apheresis. In a bone marrow transplant the stem cells are collected by surgical removal from the large marrow producing bones such as the pelvis. 

Radiation techniques differ somewhat from those used in the treatment of Hodgkin's disease. The dose of radiation therapy usually varies from 2500 to 5000 cGy and is dependent on factors that include the  type of lymphoma, the patient's stage and overall condition, the goal of treatment (curative or palliative), the proximity of sensitive surrounding organs, and whether the patient is being treated with radiation therapy alone or in combination with chemotherapy. Treatment with radiation therapy requires the use of linear accelerators with energy of 4 to 15 MV and treatment planning simulators. Simulators are used to obtain detailed x-rays of patients in the treatment position so that radiation fields can be tailored to conform to the patient's anatomy, and individually shaped protective blocks can be fabricated to shield normal tissues for the individual patient. Radiation treatment fields are tailored to individual patients and are usually limited to involved regions or extended to the immediate adjacent sites. The majority of patients who receive radiation are usually treated on only 1 side of the diaphragm. 

Patients with no symptoms (asymptomatic) who have indolent forms of advanced NHL, may  defer treatment until they become symptomatic as the disease progresses. This is generally called "Watch and Wait". Patients who are on watch and wait must be monitored  closely to watch for more aggressive behaviour or for other signs the disease if causing harm to other organs. Some patients go for years before requiring any treatment at all. However in many cases the indolent lymphoma transforms into a more aggressive type which requires immediate treatment. The risk of transformation increases with time, and with the number of previous treatments. 

Aggressive lymphomas are increasingly seen in HIV-positive patients; treatment of these patients requires special consideration.