Lymphoma is a hematologic (blood) cancer that arises in the lymphatic system, a critical part of the immune system. The lymphatic system is composed of lymphoid tissue, lymphatic vessels and lymph. Lymphoid tissue, which is primarily made of white blood cells called lymphocytes, is found in many parts of the body, including the lymph nodes, spleen, bone marrow, thymus, adenoids and tonsils, and digestive tract. Lymph nodes filter substances that travel through the lymphatic fluid. There are hundreds of lymph nodes found throughout the body. They are connected to one another by lymph vessels. Clusters of lymph nodes are found in the neck, axilla (underarm), chest, abdomen and groin (see Figure 1).

Lymphoma develops when normal lymphocytes (a type of white blood cell) transform into abnormal cancer cells. These cancer cells reproduce uncontrollably and collect in bone marrow, lymph nodes and other parts of the lymphatic system. They begin to outnumber normal cells, which can cause the lymph nodes, spleen or other organs to enlarge.

The two primary types of lymphocytes that can develop into lymphomas are B-lymphocytes (B-cells) and T-lymphocytes (T-cells):

  • Mature B-cells produce protein antibodies that attach to infectious organisms, such as bacteria and viruses, marking them for destruction.
  • T-cells can attack infectious organisms directly and help control the immune system.

Both B-cells and T-cells can transform into lymphoma cells. However, in the United States, B-cell lymphomas are much more common.

Hodgkin and non-Hodgkin lymphoma are the two main types of lymphoma. Hodgkin lymphoma can begin in any lymphoid tissue. Most commonly, it begins in the lymph nodes in the upper half of the body, such as the neck, chest and under the arms. Hodgkin lymphoma often spreads from one group of lymph nodes to others in an orderly progression.

Non-Hodgkin lymphoma (NHL) is more common than Hodgkin lymphoma. NHL occurs when T-cells, B-cells and natural killer (NK) cells grow uncontrollably. It may be found in any of the lymphoid tissues, and it spreads in a less orderly way than Hodgkin lymphoma.

More than 60 subtypes of NHL exist. These subtypes vary in microscopic appearance, molecular features, how they affect the body and how they are treated. They also grow and spread at different rates. Slow-growing types are called indolent lymphomas and fast-growing types are called aggressive lymphomas.

For both Hodgkin lymphoma and NHL, a biopsy helps identify the subtype. In addition to a physical exam and a biopsy, your doctor may also perform any of the following tests:

  • Blood tests, including a complete blood count (CBC), erythrocyte sedimentation rate (ESR), comprehensive metabolic panel, lactate dehydrogenase (LDH), beta-2 microglobulin and uric acid.
  • Bone marrow aspiration and biopsy (often done at the same time) that remove bone marrow samples for examination.
  • Lumbar puncture (spinal tap) to see if lymphoma cells are in the cerebrospinal fluid around the brain and spinal cord.
  • Specialized tests, such as cytogenetics, flow cytometry, fluorescence in situ hybridization (FISH), immunophenotyping and polymerase chain reaction (PCR).
  • Imaging tests, such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), ultrasound and X-rays, to help determine the extent of disease.


How Lymphoma is Treated

Your blood cancer diagnosis is as unique as you are, which is why you and your doctor will work closely to create your treatment plan. Your doctor will consider the stage or classification, type and location of your disease, your age and general health. You will provide input about things that are important to you, such as your expectations for quality of life. Then, together, you will define your goals of treatment. Partnering with your medical team in this way may provide you with confidence and a feeling of control as you move forward.

One or more of these common treatment options may be part of your treatment plan. They may be used alone or in combination and may change as your plan changes.

Active surveillance, also referred to as watchful waiting, is most appropriate for slow-growing disease. This option offers the possibility of avoiding the side effects of treatment for as long as possible and, hopefully, without affecting the outcome. Treatment should begin as soon as symptoms appear or test results show the disease is progressing, so it is vital to make and keep regular checkups.

Drug Therapy

This is the use of drugs designed to slow or stop the growth of cancer cells. Depending on the type of therapy, it may be used alone or with other treatments.

Chemotherapy is a systemic therapy that travels through the bloodstream and affects cells all over the body. It may be given intravenously (IV) or taken orally as a pill and is typically delivered in cycles, with treatment periods followed by rest periods to give your body time to recover. A specific strategy may consist of a single chemotherapy drug, a combination given at the same time, or drugs given one after another. It may be used alone or with other forms of treatment, such as stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy, a type of immunotherapy.

Targeted therapy uses drugs or other substances to identify and attack targets such as proteins, genes or mutations that play important roles in the growth and survival of cancer cells. Unlike chemotherapy, which attacks healthy cells as well as cancer cells, targeted therapy is designed to affect only cancer cells. Targeted therapy drugs may be given orally, subcutaneously or intravenously (IV), and some may be given in combination with other drug therapies.

Immunotherapy harnesses the potential of the body’s own immune system to recognize and destroy cancer cells. By training the immune system to respond to cancer, this strategy has the potential for a response that can extend beyond the end of treatment. Various types of immunotherapy are available depending on the diagnosis, such as immune checkpoint inhibitors, cytokines, mono-clonal antibodies, personalized vaccines and CAR T-cell therapy (see Figure 1). Immunotherapy may be used alone or in combination with other therapies.

Radiation therapy uses high-energy radiation to destroy cancer cells and shrink tumors. Some people with localized blood cancer or bone pain that does not lessen with chemotherapy may receive radiation therapy to specific parts of the body. External-beam radiation therapy is commonly used. Radiation therapy may also be given to the entire body (total body irradiation) before stem cell transplantation.

Corticosteroids are drugs used to treat some blood cancers and can ease nausea and vomiting. They can be used alone or in combination with other types of drug therapy and are given orally or through an IV.

Growth factors may be administered to help the body make white blood cells. White blood cells are often damaged by treatment, which can increase the risk of infection.

Bone-modifying drugs are given by IV to treat bone problems as well as prevent or slow further bone damage. Pain medications are sometimes combined with bone-modifying drugs to control bone pain.

Surgery, Transplantation, Trials

Surgery is not common for blood cancers but may be used to remove a single plasmacytoma (malignant plasma cell tumor), which can occur with multiple myeloma, or to remove the spleen or other organs for certain subtypes of non-Hodgkin lymphoma. Surgical procedures may be done to take a biopsy sample or, in cases of weakened bone, to place metal plates or rods that provide support or prevent fractures.

Stem cell transplantation, also known as bone marrow transplantation, is an infusion of healthy stem cells into the body, typically after chemotherapy.

Clinical trials are carefully planned and structured medical research studies that may offer access to leading-edge therapies not yet widely available. Treatment trials evaluate whether a new treatment, such as a drug or vaccine, drug combination, surgical procedure, type of radiation therapy or a combination of therapies, is more effective or better in some way than the current standard of care. They often take into consideration the individual’s genetic characteristics and other factors unique to his or her diagnosis. Ask your doctor if you should consider this valuable option as a first-line treatment (before any other treatment is given) or at any other time.