Non-Hodgkin lymphomas (NHLs) are malignancies that arise from white blood cells in the lymphatic system. More specifically, they develop from B-lymphocytic and T-lymphocytic cells, which are more commonly known as white blood cells. Unlike Hodgkin lymphomas, non-Hodgkin lymphomas do not have Reed-Sternberg cells present.
The lymphatic system is a network of tissues and organs that help our bodies fight infection and disease. It is composed of lymph vessels (carries lymph fluid around the body), lymph fluid (carries nutrients around the body and removes unwanted bacteria/viruses) and lymph nodes/glands (filters lymph fluid and empties it into the bloodstream). Some of the most well-known lymph tissues include the bone marrow, the spleen, and the tonsils.
This page will focus on chronic lymphocytic leukaemias (CLL) and small lymphocytic leukaemias (SLL), which are often grouped together and expressed as CLL/SLL. CLL and SLL are both indolent (or slow growing) types of NHL that develop from an overproduction of B-lymphocytes, and both are very similar to each other. The main difference between CLL and SLL is the location of the cancer. CLL is mostly found in the blood (like a leukaemia), whereas SLL is mostly found in lymph nodes and lymphoid tissue (like a lymphoma). CLL is also slightly more common than SLL, and they are usually staged differently.
In general, NHLs are more commonly found in men, and are generally diagnosed after the age of 60. However, anyone can develop this disease.
Treatment
If CLL/SLL is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.
Another main difference between CLL and SLL is the way that they are staged.
Staging of CLL
CLL can be staged in two different ways: the Rai staging system and the Binet staging system.
Rai Staging System
The Rai staging system divides CLL into five categories, from 0-IV, based on the degree of lymphocytosis (an increase of white blood cells), swelling of lymph nodes, enlargement of the spleen and/or liver, and low levels of red blood cells (RBCs) and/or platelets.
- Rai stage 0: lymphocytosis occurs with no enlargement of the lymph nodes, liver or spleen and normal RBC and platelet counts.
- Rai stage I: lymphocytosis occurs with enlarged lymph nodes. There is no enlargement of liver or spleen, and RBC and platelet counts are either normal or slightly below normal.
- Rai stage II: lymphocytosis occurs with an enlarged spleen. An enlarged liver and/or enlarged lymph nodes may be present. RBC and platelet counts are either normal or slightly below normal.
- Rai stage III: lymphocytosis occurs with anaemia (low RBCs). An enlarged spleen, liver, and lymph nodes may be present. Platelet counts are normal or slightly below normal.
- Rai stage IV: lymphocytosis occurs with thrombocytopenia (low platelet count). Anaemia and enlarged liver, spleen, and/or lymph nodes may be present.
The Rai staging system is mainly used in the United States, but some doctors in Australia may use this system.
Binet Staging System
The Binet staging system divides CLL into three categories, from A-C, based on lymphocytosis, enlargement of lymph tissue, and blood counts.
- Stage A: lymphocytosis occurs with less than three areas of enlarged lymph tissue.
- Stage B: lymphocytosis occurs with more than three areas of enlarged lymph tissue.
- Stage C: lymphocytosis occurs with low levels of RBCs and/or platelets, enlarged spleen and/or lymph nodes.
The Binet staging system is the most common way to stage CLL in Australia.
Staging of SLL
In addition to the systems used in CLL staging, SLL may also be staged using the Lugano classification, which may also be referred to as a modification of the Ann Arbor staging system. In this system, SLLs are assigned numerical values, from stage I-IV:
- Stage I: cancer cells are confined to a single lymph node area, either above or below the diaphragm (large muscle separating the abdomen from the chest). This stage is also known as early-stage cancer.
- Stage II: cancer cells have spread to two or more lymph node areas on the same side of the diaphragm. This is also known as localised cancer.
- Stage III: the cancer has become larger and affected lymph node areas on both sides of the diaphragm. This is also known as localised cancer.
- Stage IV: Lymphoma is in multiple lymph node areas and may be present in other parts of the body, such as bone marrow, liver, and/or lungs. This is also known as advanced or metastatic cancer.
In addition to the numerical system, your doctor may also stage your cancer with a letter, which gives more information about your symptoms and how your body is being affected by the disease. These letters include:
- A – You feel well and have no B-symptoms of lymphoma.
- B – You have some or all of the B-symptoms of lymphoma.
- E – You have NHL in an organ that is not a part of the lymphatic system (such as lungs, skin, bladder etc.).
- X – You have a tumour that is greater than 10cm in size. This is also called ‘bulky disease’.
- S – You have a lymphoma in your spleen.
Grading of CLL/SLL
As both cancers discussed on this page are classified as ‘indolent’, these cancers are both low-grade.
Treatment Options for CLL/SLL
Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, age, stage of disease and overall health.
Treatment options for CLL/SLL may include:
- Watch and wait.
- Chemotherapy.
- Targeted therapy, potentially including:
- Monoclonal antibodies.
- Bruton tyrosine kinase (BTK) inhibitors.
- Stem-cell transplant.
- Corticosteroids (usually in combination with chemotherapy).
- Blood and/or platelet transfusions.
- Surgery to remove the spleen (splenectomy) (only in extreme cases).
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
While the cause of CLL/SLL remains unknown, the following factors may increase the likelihood of developing the disease:
- Genetic mutations of genes associated with blood development.
- Family history of CLL/SLL.
- Exposure to certain chemicals.
- High doses of radiation.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
Most patients with a CLL/SLL will appear asymptomatic in the early stages of disease. As symptoms progress, some of the following symptoms may appear:
- Easy bruising and/or bleeding.
- Painless lump in the neck, underarms, groin, and/or other areas.
- B-symptoms, which include:
- Drenching night sweats.
- Unexplained weight loss.
- Persistent fevers over 37.5°C.
- Fatigue.
- Itchy skin.
- Recurrent infections.
- Shortness of breath.
- Low blood counts, potentially including anaemia (deficiency of red blood cells in the body), thrombocytopenia (deficiency of platelets in the body), and/or neutropenia (deficiency of neutrophils (a type of white blood cell) in the body), which may cause the following symptoms:
- Shortness of breath.
- Fatigue.
- Dizziness.
- Confusion.
- Difficulty concentrating.
- Paleness.
- Abnormal protein levels, which may cause the following symptoms:
- Poor circulation (causing blue fingers and/or toes, numbness and/or tingling in fingers and toes etc.).
- Confusion.
- Headaches.
- Nosebleeds.
- Blurred vision.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a CLL/SLL, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Blood tests
Your doctor will recommend a blood test for check for signs of lymphoma and determine overall health. The most common test is a full blood count, which will analyse the levels of red blood cells, white blood cells and platelets in the blood. Low counts in any of these categories could be indicative of disease.
Imaging
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), ultrasound, and/or positron emission tomography (PET scan), to check for signs of tumours and/or metastasis.
Biopsy
Once the location of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. In most cases, this may be done by either an excision biopsy (where the lymph node is completely or partially removed), a fine needle biopsy (a fine needle is inserted into the lymph node to remove a sample), or a core needle biopsy (where a bigger needle is inserted into the lymph node to remove a sample). Both procedures are often performed as a day surgery. In rare cases, a bone marrow biopsy may be performed to see if it contains any cancerous cells. This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for cancer cells.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage CLL/SLLs have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.