Non-Hodgkin lymphoma (NHL) is a cancer that starts in lymphocytes, which are white blood cells that help fight infection. Lymphocytes are present in the bloodstream, but also in the lymphatic system and throughout the body. NHL most commonly affects adults and is more common than the other major types of lymphoma, Hodgkin lymphoma.
NHL refers to many different types of lymphomas that all share some common features. However, different types of NHL can behave very differently. The most common type is diffuse large B-cell lymphoma (DLBCL), an aggressive lymphoma. Other types may be lazier, or grow more slowly. Some can be cured, some cannot. NHL treatment may include any number of agents, such as chemotherapy, radiation therapy, monoclonal antibodies, small molecules, cell therapy, or stem cell transplantation.
Signs and symptoms of non-Hodgkin lymphoma may include:
- Painless, swollen lymph nodes
- abdominal discomfort or fullness
- chest pain, shortness of breath, or cough
- easy bruising or bleeding
- Fever, night sweats, or unexplained weight loss
Systemic symptoms of inflammation, or “B” symptoms, sometimes occur in NHL, including unexplained fever, night sweats, and unexpected weight loss of more than 10% of normal body weight over 6 months. B symptoms are no longer routinely used in the NHL staging system because they often do not provide independent information about your prognosis.
The etiology of most lymphomas is unknown; however, over the past 15 years, scientists have made tremendous progress in understanding the role of certain genes in certain types of NHL, leading to the emergence of newer targeted therapies .
In addition, many risk factors for NHL are known, including advanced age, a weakened immune system, certain autoimmune diseases, certain infections, and exposure to radiation, certain chemicals, or certain drugs.
What causes non-Hodgkin lymphoma?
Although personal and family medical histories may be relevant, NHL cannot be diagnosed by symptoms or medical history alone. Many tests are used to diagnose non-Hodgkin lymphoma, including:
- During the physical examination, check the neck, underarms, and groin for swollen lymph nodes, and check the abdomen for swollen spleen or liver.
- Blood and urine tests can be used to rule out other causes of the same symptoms, such as infections that cause fever and swollen lymph nodes, rather than lymphoma.
- Imaging tests such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) may be done to determine the extent of disease, if present. Radiologists interpreting CT scans follow specific guidance on what constitutes normal lymph node size; PET and fluorodeoxyglucose (FDG PET) scans can be used to locate diseased areas in the body based on increased glucose uptake or affinity.
- A lymph node biopsy may be recommended to obtain a suspicious lymph node sample for laboratory testing. The sample is evaluated by a pathologist, and tests done in the lab can show if you have NHL, and if so, what type.
- In some cases, additional testing may be performed on the genetic profile of your specific type of NHL to help understand the level of risk and plan treatment.
- Bone marrow biopsy and aspiration procedures can be performed to remove a sample of bone marrow. Analyze the sample for NHL cells.
- Depending on your situation, other tests and procedures may be used.
A staging system called the Lugano classification is currently used for NHL patients. However, this staging system is generally less useful for NHL than for Hodgkin lymphoma, which tends to spread more methodically, extending from initially involved lymph nodes.
Most patients with aggressive NHL have advanced disease (ie, stage III/IV) at diagnosis. Therefore, staging is performed in the NHL to identify a small number of patients with early-stage disease and, along with other factors, help understand prognosis and determine the possible impact of treatment.
The prognosis of NHL largely depends on the type of NHL and its specific characteristics, including microscopic, molecular, and genetic features. For example, diffuse large B-cell lymphoma, follicular lymphoma, and peripheral T-cell lymphoma are three distinct types of NHL, each with important differences in the factors or prognostic indicators used to try to determine prognosis.
The individual’s age and overall health, as well as whether the lymphoma is confined to the lymph nodes or outside the lymph nodes (extranodal), are also prognostic factors.While the number and location of lesions in the body (important in Lugano staging) did not must Shaping prognosis, the total amount of NHL, or tumor burden, can be an important factor in prognosis and treatment.
Among the different types of NHL, high- or intermediate-grade lymphomas described by pathologists often grow rapidly in the body, so both types are considered aggressive NHL. In contrast, low-grade NHL grows slowly, so these lymphomas are called indolent NHL. Indolent NHLs generally do not cause as many symptoms as aggressive NHLs, but they may also be more difficult to eradicate and less likely to be cured. The most common indolent lymphoma is follicular lymphoma. Over time, a small percentage of indolent lymphomas, such as follicular lymphomas, turn into aggressive lymphomas.
The correct treatment of a patient with NHL depends not only on the disease itself, but also on the person being treated and their age, overall health, preferences, and goals of treatment.
When lymphoma appears to be slow-growing or indolent, sometimes no treatment or watchful waiting may be an option. Indolent lymphomas that do not cause any signs or symptoms may not require treatment for many years. When watch and wait is an option, it’s usually because the data show that, for your particular disease, at the stage of your journey, delaying treatment and its potential side effects is as good or better than stopping it. Start now – waiting won’t sacrifice your long-term results.
Today, there are many drugs available to treat NHL, either alone or in combination, depending on the situation. Any of the following may be part of an NHL treatment regimen.
Chemotherapy drugs can be given alone, in combination with other chemotherapy drugs, or in combination with other treatments. Cytoxan (cyclophosphamide) is an example of a chemotherapy drug used to treat some NHLs. Due to concerns about toxicity, not all patients are eligible to receive chemotherapy in the full dosing regimen.
Radiation therapy can be used alone or in combination with other cancer treatments. Radiation can be directed to the affected lymph nodes and areas near the lymph nodes where the disease may progress. Only some people with certain types of NHL usually receive radiation therapy.
Novel drugs include monoclonal antibodies that target lymphocytes and small molecules that target specific steps in pathways that cancer cells rely on. Newer drugs are generally less toxic than chemotherapy, but they still have toxicities that are considered part of the risks and benefits of treatment.
- Rituxan (rituximab) and obinutuzumab are examples of monoclonal antibodies that are used in combination with other drugs to attack B lymphocytes in the treatment of certain types of NHL.
- Imbruvica (ibrutinib) and Venclexta (venetoclax) are examples of small molecules that target cell signals and steps important to B lymphocytes. These drugs are used to treat certain patients with chronic lymphocytic leukemia (CLL) and its “cousin” small lymphocytic lymphoma (SLL), a type of NHL. Many people think that CLL and SLL are the same disease, except where most of the disease is located in the body. Imbruvica is also approved for the treatment of marginal zone lymphoma and mantle cell lymphoma.
Chimeric antigen receptor (CAR) T-cell therapy can be used when other treatments stop working. CAR T cell therapy is a type of immunotherapy that modifies a patient’s own T cells to help destroy cancer cells. T cells are collected from a patient’s blood and sent to a lab to be modified to suit the type of CD markers expressed by the cancer cells. Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel) are examples of CAR-T treatments approved for certain NHL patients.
For some patients with certain types of NHL, a bone marrow transplant or stem cell transplant is an option.
Clinical trials investigating new therapies and new treatment options, which frequently recruit NHL patients, may also be considered.
Regardless of the type of lymphoma affecting your life, it is important to understand the disease and understand treatment options. Doctors and patients are on the same team, and a diagnosis is only the first step in a potentially long journey with lymphoma.
NHL represents a distinct collection of lymphomas. Some, like some low-risk cases of small lymphocytic lymphoma, may never need treatment. Others, such as the classic case of aggressive mantle cell lymphoma, may require aggressive treatment early on in an attempt to preserve a person’s lifespan. DLBCL, the most common form of NHL, is an example of an aggressive form of NHL that has the potential to be cured with modern treatments.