Lymphoma

What is lymphoma?

Lymphoma is an umbrella term describing dozens of cancers that begin in the immune system. Lymphomas are the most common type of blood cancer, and are broadly categorized as either Hodgkin or non-Hodgkin disease. All lymphoma subtypes combined are the seventh most common cancer in the United States.

This year, approximately 74,690 adults and children in the United States will be diagnosed with non-Hodgkin lymphoma and about 8,500 with Hodgkin lymphoma, according to the American Cancer Society. About 90 percent of people with lymphoma are diagnosed with non-Hodgkin lymphoma.

Hodgkin lymphoma

Hodgkin lymphoma occurs when white blood cells called B-lymphocytes become abnormal and begin growing and dividing so fast that normal cells in the immune system cannot keep up. Hodgkin lymphoma cells are called Reed-Sternberg – large cells with more than one nucleus that resemble “owl’s eyes.” Hodgkin lymphoma is rarer than non-Hodgkin and is most common among young people.

Non-Hodgkin lymphoma

Non-Hodgkin lymphoma occurs when either B or T cell lymphocytes become abnormal. In most cases it is the B cells that are defective. Non-Hodgkin lymphomas are categorized based on a spectrum of how they behave in the body:

• Indolent (low grade) develop slowly, over years. These cancers are considered chronic – treatable but not generally curable because they tend to come back even after successful treatment.
• Aggressive (intermediate grade) lymphomas grow quickly over the course of months and are treatable and potentially curable.
• Highly aggressive (high grade) lymphomas develop very quickly – within weeks – and are highly curable, especially with chemotherapy.

Hodgkin and non-Hodgkin tend to behave differently in the body and treatments for each disease differ.

How lymphoma develops

Lymphoma is not just one disease but a large, complex group of blood cancers that start in a part of the immune system called the lymphatic system. This system of tissues, organs and vessels is made up of pea-sized organs (called nodes) where white blood cells cluster, connected by thin tubes (called vessels). Because this system is so widespread, cancers involving the lymphatic system can begin in almost any body part.

An abnormal immune response

Lymphoma develops when lymphocytes – infection-fighting white blood cells in the immune system – become abnormal and grow and divide uncontrollably into tumors. Lymphocytes are the main part of the immune system and circulate throughout the body responding to bacteria and viruses.

With lymphoma, abnormal white blood cells grow in number (also causing the lymph nodes to swell) not because of an infection, but because of a defect inside the cells. Instead of fighting disease, these cells, which have no real purpose in the body, grow and take up space. In contrast to a normal immune response, with lymphoma, swelling in the lymph nodes does not subside.

What are the Types of lymphoma?

There are dozens of lymphoma types – all related, yet appearing and acting differently in the body. While lymphoma is a rare disease overall some types are more commonly diagnosed including:

• Diffuse large B cell lymphoma, the most common type of non-Hodgkin lymphoma, is a fast-growing cancer that tends to start in lymph nodes in the upper part of the body such as the chest, neck, abdomen or armpit.
• Follicular lymphoma, the second most common type of non-Hodgkin lymphoma, tends to start in lymph nodes throughout the body and the bone marrow. This typically slow-growing (indolent) disease can, over time, become a more aggressive type.
• Cutaneous T cell lymphomas involve the skin, and tend to start with rash, intense itching, dry skin, pain and enlarged lymph nodes. The most common CTCLs include mycosis fungoides and Sezary syndrome.
• Small cell lymphocytic lymphoma and chronic lymphocytic leukemia are the same disease but found in different areas of the body. SLL cells tend to be found in lymph nodes while CLL cells are in the blood and bone marrow.
• Marginal zone lymphomas
• Mucosa-associated lymphoid tissue lymphoma, or MALT, also called extranodal marginal zone lymphoma, develops outside the lymph nodes in organs like the stomach, thyroid, eyes, small intestine and lungs.
• Nodal marginal zone lymphoma occurs within the lymph nodes.
• Splenic marginal zone lymphomas develop in the spleen and blood and are associated with hepatitis C infection.
• Waldenstrom macroglobulinemia begins when the body produces too much of a protein called immunoglobulin, which thickens the blood. Waldenstrom cells may crowd out normal cells in bone marrow, like red and white blood cells and platelets.
• AIDS-related lymphoma develops in patients who have acquired immune deficiency syndrome. Patients with weakened immune systems are at significantly greater risk of lymphoma.
• Anaplastic large cell lymphoma is rare type of lymphoma that can appear in lymph nodes, organs within the body or the skin. Anaplastic large cell and cutaneous lymphomas are among several subtypes of peripheral T cell lymphoma.
• Burkitt lymphoma is one of the fastest-growing types of lymphoma affecting both adults and children. It is most often associated with Epstein-Barr virus infection but can occur in anyone who has a weakened immune system.
• Central nervous system lymphoma develops in lymph tissue located in the brain and spinal cord.
• Lymphoblastic lymphoma is a rare form of non-Hodgkin lymphoma, involving abnormal B or T cells, which most often affects children.
• Mantle cell lymphoma develops from cancerous cells in what is called the mantle zone (outer edge) of a lymph node. It can be fast- or slow-growing and may spread to the gastrointestinal tract and bone marrow.
• Composite lymphoma is a rare type that is composed of several different types of lymphoma cells.

What increases your risk of lymphoma?

Things that put you at higher risk for getting lymphoma are called risk factors. Doctors do not know what causes most lymphomas, and there is very little that can be done to avoid being diagnosed. For most patients, it is not one but a combination of factors that likely contributes to developing lymphoma. Risk factors for lymphoma include:

• Immune system problems, including having HIV/AIDS other autoimmune diseases and being on immune-suppressing medication, is the most recognized risk for lymphoma.
• Age increases the risk of most cancers, including lymphoma.
• Sex is a risk factor; males are more likely than females to be diagnosed.
• Race increases risk; Caucasians are more likely to develop lymphoma.
• Previous cancer treatment with chemotherapy and radiation can increase risk.
• Infections such as the Epstein-Barr virus, human T cell leukemia virus type 1 and human herpes virus-8 increase risk of certain lymphoma subtypes. Other infections such as chlamydia, helicobacter pylori and hepatitis C are also associated.
• Family history, such as having a brother, sister or parent with lymphoma, can slightly increase risk of certain lymphomas.
• Chemicals, pesticides and exposure to other toxins like Agent Orange and benzene may be linked to developing lymphoma.
• Obesity or being overweight is associated with developing several cancers and, in some studies, has shown an association with lymphoma.

What are the symptoms of Lymphoma?

Usually there are no early warning signs of lymphoma so it tends to be diagnosed during later stages. Some of the first signs of lymphoma are the same as other illnesses, including swollen lymph nodes, cough and fever, making it difficult to diagnose early-on. The most common symptoms of lymphoma include:

• Fever
• Swollen lymph nodes (in the neck, armpits or groin) that do not go away
• Severe itching all over the body
• Excessive sweating, especially at night
• Unexplained weight loss
• Unusual tiredness or weakness that does not go away
• Abdominal discomfort, pain or fullness when eating (due to an enlarged spleen)
• Low red blood cell count
• Shortness of breath or persistent cough
• Chest pain or pressure

While swollen lymph nodes associated with lymphoma may first appear in any body part, swelling associated with Hodgkin lymphoma is more likely to start in the upper body, including the neck, chest and sometimes the abdomen.

Symptoms of other medical conditions may mirror those of lymphoma. If you are treated for those conditions, or if your symptoms last for several weeks despite medical treatment, you may need further consultation to rule out lymphoma.

Lymphoma prevention

Maintaining a healthy weight and diet has been shown in some studies to lower the risk of developing lymphoma. Studies have linked eating a diet rich in fruits and vegetables with substantially reduced risk of lymphoma and, as with many cancers, being physically active and not overconsuming products with animal fats may also help.

Lymphoma is a large group of cancers with overlapping features – and since every patient’s disease looks different, getting an accurate diagnosis can be the most challenging part of treatment. The differences between lymphoma tumors is subtle and, since lymphoma involves immune system cells, it may be difficult to distinguish it from a normal infection.

For these reasons treatment at City of Hope begins with leading-edge diagnostics, performed by world-renowned hematopathologists who are well versed about the entire spectrum of this disease. This powerful combination of experience, next generation technology and talent is why City of Hope is known for transforming lymphoma patients with advanced or misdiagnosed disease – and dire diagnoses – into survivors.

How lymphoma is diagnosed

Lymphoma is diagnosed using biopsy, which involves removing a small sliver of tissue or an entire lymph node, and examining it under a microscope. A biopsy may be performed using a needle, or with surgery, and the tissue is tested to determine:

• The type of abnormal cell involved in the lymphoma
• The size of the cell involved (small or large cell)
• The type of cell affected (B or T cell)
• Whether it is fast- or slow-growing
• Abnormalities inside the cell driving the lymphoma
• What markers are on the lymphoma cell surface

We perform several tests on the tissue to arrive at the most accurate diagnosis. Once a diagnosis is determined, other tests may be performed to figure out where lymphoma is in the body and the stage of disease.

If cancer is suspected, we may perform other tests to better visualize the cancer and determine if it has spread, including:

• Imaging tests: CT, PET and MRI scanning
• Bone marrow aspiration: taking a small sample of marrow cells from inside the bone
• Bone marrow biopsy: removing a small sample of bone along with the marrow

These tests also serve as a baseline used later to assess your response to treatment.

What are the stages of Lymphoma?

When lymphoma is found early, it tends to be confined to one or more lymph nodes. More advanced disease occurs when cancer cells have spread beyond the lymph system into organs like the liver, skin, brain, bone or other tissues. Lymphoma stages include:

• Stage 1, when one lymph node area (for example, the side of neck or under arm) is involved
• Stage 2, when two or more lymph node areas are involved but on same side of the diaphragm – either all below or above
• Stage 3, when more than one lymph node area on both sides of the diaphragm is involved
• Stage 4, widespread disease that has gone beyond the lymphatic system, most commonly to the bone marrow or liver, but also the skin, brain, bone and other tissues

Within each stage, the disease is categorized as either symptomatic or asymptomatic – either causing symptoms or not.

What are the treatment options for lymphoma?

City of Hope’s approach to treating lymphoma starts with a coordinated, multidisciplinary care team whose main goals are helping you to live a long, healthy, cancer-free life.

The newest therapies and treatment combinations, tailored to your specific type of lymphoma, are what guide your treatment. Our lymphoma specialists offer leading-edge therapies – and specialize in treating difficult lymphomas, including both aggressive and slow-growing disease.

Combination treatment

The most common treatment for both Hodgkin and non-Hodgkin lymphoma is combination chemotherapy. Newer treatments such as radiation, targeted therapy and immunotherapy often are combined with chemotherapy to increase the chances treatment will be effective. Factors that determine your treatment course include:

• Type of lymphoma
• Stage and category of the disease
• Response to prior treatment
• Whether the disease has come back after treatment
• Whether other medical problems such as heart or kidney disease are involved

Our goal for your treatment is improving the chances of a cure while ensuring that, along the way, your therapy is of the lowest toxicity so that you can maintain your quality of life.

Skin lymphoma experts

Skin lymphomas are rare and often debilitating diseases. We are one of the only cancer centers in the country with world experts on cutaneous lymphomas, including:

• Cutaneous T cell lymphoma
• Follicle center lymphoma
• Marginal zone B cell lymphoma
• Diffuse large B cell lymphomas of the leg and other areas

These are some of the most difficult lymphomas to diagnose since they resemble other common skin conditions like eczema, psoriasis and ringworm. Our team includes hematopathologists able to discern the difference between skin lymphoma subtypes, and are responsible for groundbreaking skin-directed and light therapies to treat them once they are diagnosed.

Bone marrow and stem cell transplantation leaders

For patients with recurrent or particularly aggressive disease, transplantation may be a treatment option. City of Hope is a world leader in setting standards for stem cell transplantation and improving long-term outcomes for both children and adults. Using innovative approaches for blood and bone marrow transplantation to treat lymphoma has led our Hematologic Malignancies and Stem Cell Transplantation Institute to be considered an industry leader with unrivaled survival rates.

Learn more about our bone marrow and stem cell transplantation program.

AIDS-related lymphoma

City of Hope scientists pioneered the use of blood stem cell transplants to treat patients with HIV and AIDS-related lymphoma, changing the standard of care. They used a new form of gene therapy to achieve the first long-term persistence of anti-HIV genes in patients with AIDS-related lymphoma. This treatment ultimately may cure not only lymphoma, but also HIV/AIDS.

Improving outcomes

Diagnosis, treatment and cure rates for lymphoma are improving every year, and research at City of Hope has helped to fuel those trends and improve outcomes among our patients.

Leading-edge clinical trials, collaborations with a large network of institutions and our designation as a lymphoma Specialized Program of Research Excellence provide our patients with exciting new treatment options.

And City of Hope’s unique ability to produce and manufacture the agents being developed by our investigators means treatments get to our patients faster.

Chemotherapy

Each day that our patients continue to spend with their loved ones is a testament to the strides we are making in understanding and beating treatment-resistant lymphomas." Robert Chen, M.D., hematologist

Chemotherapy, the most common treatment for lymphoma, uses drugs to either kill cancer cells or stop them from growing. This approach is usually necessary to kill cancer cells circulating throughout the lymphatic system.

Exciting advances in chemotherapy at City of Hope are allowing patients with advanced disease to get drug combinations – including combining targeted therapies, radiotherapies and immunotherapies with chemotherapy – designed to slow down disease progression and improve quality of life.

Immunotherapy

Immunotherapy is a way of awakening the immune system to action against cancer cells. Immune cells patrol the body in search of disease, but cancer cells often devise ways to get around or suppress them. City of Hope is developing and testing drugs that can unleash dramatic and specific immune responses to cancer cells – or make them visible to the immune system.

Many of the clinical trials at City of Hope are exploring immunotherapy to treat lymphoma, including exciting advances in CAR T cell therapy that have resulted in both partial and complete remissions.

Targeted Therapies

City of Hope uses the latest technology to spot genetic vulnerabilities in cancer cells and use medications to stop them from growing. Knowing how a tumor behaves and how it would respond to different therapies allows us to created targeted therapies: drugs or drug combinations that would work best to treat specific cancers.

Monoclonal antibodies

A recent trial led by City of Hope – involving the targeted therapy brentuximab vedotin – cured or extended the lives of several patients who had failed multiple therapies. Brentuximab vedotin is one of an exciting new class of drugs called monoclonal antibodies, which target specific molecules on the surface of cancer cells to stimulate a response. These drugs are a normal part of therapy for many of our patients.

Small molecules

We are investigating small molecules that interfere with the defective signaling inside cancer cells that help them to grow and divide uncontrollably. These drugs are often given in pill form and have significantly fewer side effects than chemotherapy.

Radiation Therapy

Radiation therapy uses high-energy radiation to kill cancer cells and shrink tumors. It is one of the most effective treatments for lymphoma and often is paired with other treatments. City of Hope offers advanced radiation treatments that are highly targeted to cancer cells while protecting the surrounding normal tissue.

One technique, TomoTherapy, includes delivering focused radiation to the entire bone marrow compartment. The technique, called total marrow irradiation, is an effective way to target cancer cells while reducing side effects. And we are actively investigating a leading-edge radioimmunotherapy, a way to direct radioactive particles toward cancer cells and kill them.

Our approach to radiation for patients with chronic types of lymphoma is to monitor and sometimes limit the number of scans each patient has in an effort to reduce the dose of radiation exposure – and our radiologists have protocols designed to limit the amount of radiation delivered with each scan.