Non-Hodgkin lymphomas (NHLs) are malignancies that arise from white bloodthe red bodily fluid that transports oxygen and other nutrients around the body cellsthe basic structural and functional unit of all living things in the lymphatic systema network of tissues and organs that help our bodies fight infection and disease. 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 infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body and disease. It is composed of lymph vesselsa network/chain of thin tubes that moves lymph fluid around the body, lymph fluida clear watery fluid that carries nutrients around the body and removes unwanted bacteria/viruses and lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid/glands. Some of the most well-known lymph tissues include the bone marrowsoft, spongy tissue found in bones that makes blood cells, the spleen, and the tonsils.
This page will focus on chronica long-lasting disease that changes slowly over time 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 cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. CLL is mostly found in the blood (like a leukaemiacancer of blood and/or blood forming tissues), whereas SLL is mostly found in lymph nodes and lymphoid tissuea group of cells that work together to perform a function (like a lymphomacancers of the lymphatic system). 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, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding.
- 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 anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection (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 thrombocytopenialow levels of platelets in the blood (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 nodea small lump or mass of tissue in your body area, either above or below the diaphragm (large muscle separating the abdomenstomach, stomach area, belly 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 localisedaffecting only one area of body 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 advancedat a late stage, far along 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, bladdera hollow, muscular sac in the pelvis that stores urine etc.).
- X – You have a tumoura tissue mass that forms from groups of unhealthy cells 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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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 waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Targeted therapymedication that targets specific molecular features of cancer cells, potentially including:
- Monoclonal antibodies.
- Bruton tyrosine kinase (BTK) inhibitors.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Corticosteroidsa type of anti-inflammatory medication that is used to treat inflammation (usually in combination with chemotherapy).
- Transfusion therapya procedure where blood or blood components are transferred into your bloodstream.
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove the spleen (splenectomyremoval of the spleen) (only in extreme cases).
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
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 riskthe possibility that something bad will happen 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.
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, groinarea between the abdomen and thighs, and/or other areas.
- B-symptoms, which include:
- Drenching night sweats.
- Unexplained weight loss.
- Persistent fevers over 37.5°C.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Itchy skin.
- Recurrent infections.
- Dyspneadifficulty breathing, shortness of breath.
- Cytopenialow levels of red blood cells, white blood cells or platelets in the blood; one or more blood cell type can be affected, potentially including anaemia, thrombocytopenia, and/or neutropeniaa condition where there are low levels of neutrophils (a type of white blood cell) in the body, which may cause the following symptoms:
- Dyspnea.
- 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
If your doctor suspects you have a CLL/SLL, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including a CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow..
- Biopsyremoval of a section of tissue to analyse for cancer cells.
