An Overview of Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is a cancer that starts in lymphocytes, a type of white blood cell that helps fight infection.

Lymphocytes are found in the bloodstream but also in the lymph system and throughout the body. NHL most often affects adults and is more common than the other major category of lymphoma, Hodgkin lymphoma. 

This article will provide an overview of the symptoms, causes, diagnosis, treatment, and prognosis associated with NHL.

NHL refers to many different types of lymphoma that all share some characteristics. 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 more indolent, or slow-growing. Some can be cured, while others cannot. NHL treatments may include any number of agents such as chemotherapy, radiation, monoclonal antibodies, small molecules, cellular therapies or stem cell transplant.

Symptoms

Signs and symptoms of non-Hodgkin's lymphoma may include:

• Painless, enlarged lymph nodes
• Fatigue
• Abdominal discomfort or fullness
• Chest pain, shortness of breath, or cough
• Easy bruising or bleeding
• Fever, night sweats, or unexplained weight loss

Systemic symptoms that come from inflammation, or "B” symptoms, sometimes occur in NHL and include unexplained fever, drenching night sweats, and unintentional weight loss greater than 10 percent of normal body weight over six months. B symptoms are no longer routinely used in the staging system for NHL because such symptoms tend not to provide independent information about your prognosis.

Causes

The cause of most lymphomas is not known; however, scientists have gained tremendous ground in understanding the role of certain genes in certain types of NHL in the last 15 years, and newer, targeted therapies have emerged as a result. 

Additionally, a number of risk factors for NHL are known, including advanced age, having a weakened immune system, certain autoimmune diseases, certain infections, and exposures to radiation, certain chemicals or certain drugs.

Diagnosis

While personal and family medical history may be relevant, NHL is not diagnosed by symptoms or history alone. A number of tests are used to diagnose non-Hodgkin's lymphoma, including the following:

• In the physical exam, the neck, underarm and groin are checked for swollen lymph nodes, and the abdomen is checked for a swollen spleen or liver. 
• Blood and urine tests may be used to rule out other causes that could produce the same symptoms, such as an infection causing fever and swollen lymph nodes, rather than lymphoma.
• Imaging tests such as X-ray, computerized tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) may be done to determine the extent of disease, if present. Radiologists who interpret CT scans follow specific guidance about what constitutes normal lymph node size; PET with fluorodeoxyglucose (FDG PET) scanning may be used to locate areas of disease in the body, based on increased glucose uptake, or avidity.
• A lymph node biopsy may be recommended to obtain a sample of a suspect lymph node for laboratory testing. Samples are evaluated by pathologists, and tests performed in the laboratory can show whether you have NHL, and, if so, which type.
• Additional testing of the genetic profile of your particular type of NHL may be done in some instances, to help understand the level of risk and plan treatment.
• A bone marrow biopsy and aspiration procedure to remove a sample of bone marrow may be performed. The sample is analyzed to look for NHL cells. 
• Other tests and procedures may be used depending on your situation.

Staging

A staging system called the Lugano classification is the current staging system used for patients with NHL. However, this staging system is oftentimes less useful for NHL than for Hodgkin lymphoma, the latter of which tends to spread more methodically, extending from the originally involved lymph node.

Most patients with aggressive NHL have advanced-stage disease (i.e., stage III/IV) at diagnosis. Thus, staging is done in NHL to identify the small numbers of patients with early-stage disease and to help, in concert with other factors, understand the prognosis and determine the likely impact of treatment.

Prognosis

The prognosis of NHL depends in large part on the type of NHL and its particular characteristics, including microscopic, molecular and genetic characteristics. For example, diffuse large B-cell lymphoma, follicular lymphoma, and peripheral T-cell lymphoma are three different types of NHL, and each has important differences in the factors that are used to try to determine the prognosis, or prognostic index.

An individual’s age and overall health, as well as whether or not the lymphoma is confined to or outside the lymph nodes (extra-nodal), also are factors in the prognosis. While the number and location of disease spots in the body (which are important in Lugano staging) do not necessarily shape the prognosis, the total amount of NHL, or tumor burden, can be an important factor in prognosis and treatment.

Across the different types of NHL, what the pathologist describes as a high-grade or intermediate-grade lymphoma usually grows fast in the body, so these two types are considered aggressive NHL. In contrast, low-grade NHL grows slowly, and these lymphomas are therefore called indolent NHL. Compared with aggressive NHLs, indolent NHLs typically do not give rise to too many symptoms, but they also may be harder to eradicate and are less likely to be cured. The most common kind of indolent lymphoma is follicular lymphoma. A small subset of indolent lymphomas such as follicular lymphoma transforms into aggressive lymphomas over time.

Treatment

The right treatment for an individual with NHL depends not only on the disease, itself, but also on the person being treated and their age, overall health, preferences, and goals for treatment.

When the lymphoma appears to be slow-growing, or indolent, sometimes a period of no treatment, or watch and wait, may be an option. Indolent lymphomas that are not causing any signs or symptoms may not require treatment for years. When watch and wait is an option, it is usually because data show that, for your particular disease, at your stage of the journey, it is just as good, if not better, to hold off on treatment and its potential side effects than to start immediately—and that waiting doesn’t sacrifice your long-term outcomes.

Today, a number of agents are available to treat NHL, and they may be used alone or in combination, depending on the circumstances. Any number of the following may be a component of a treatment regimen for NHL.

Chemotherapy agents can be given alone, in combination with other chemotherapy agents, or combined with other treatments. Cytoxan (cyclophosphamide) is an example of a chemotherapy agent used in the treatment of certain NHLs. Not all patients are candidates for chemotherapies at their full dosing schedules due to concerns about toxicities.

Radiation therapy can be used alone or in combination with other cancer treatments. Radiation can be aimed at affected lymph nodes and the nearby area of nodes where the disease might progress. Only certain people with certain NHL types are customarily offered radiation therapy.

Novel agents include monoclonal antibodies that target lymphocytes and small molecules that target specific steps in the pathways that the cancer cells rely on. Novel agents are often not as toxic as chemotherapy, but they still come with toxicities that are considered as part of the risks and benefits of treatment.

• Gazyva (obinutuzumab), Lunsumio (mosunetuzumab), and Rituxan (rituximab) are examples of monoclonal antibodies, and they are used to attack B-lymphocytes in combination with other agents in the treatment of certain types of NHL.
• Imbruvica (ibrutinib) and Venclexta (venetoclax) are examples of small molecules that target cellular signals and steps that are important to B-lymphocytes. These agents are used to treat certain patients with chronic lymphocytic leukemia (CLL) and its “cousin” small lymphocytic lymphoma (SLL), which is a type of NHL. Many consider CLL and SLL the same disease, save for the location of the bulk of the disease in the body. Imbruvica is also approved to treat marginal zone lymphoma and mantle cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy may be used when other treatments stop working. CAR T-cell therapy is an immunotherapy treatment that modifies the patient’s own T-cells to help destroy cancer cells. T-cells are collected from the patient’s blood sent to a lab where they are modified to fit the type of CD markers expressed by the cancerous cells. Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel) are examples of CAR-T treatments approved for certain people with NHL.

Bone marrow transplant or stem cell transplant is an option for some patients with certain types of NHL.

Clinical trials investigating new therapies and new treatment regimens are often recruiting patients with NHL and can be considered as well.

A Word From Verywell

Regardless of the type of lymphoma that has touched your life, it is important to learn about the disease and to understand the options for treatment. Doctors and patients are on the same team, and diagnosis is just the first step of a potentially long lymphoma journey.

NHL represents a diverse collection of different lymphomas. Some, like certain low-risk cases of small lymphocytic lymphoma, may never require treatment. Others, such as typically aggressive cases of mantle cell lymphoma, may require aggressive treatment, early on, to try to protect a person’s lifespan. DLBCL, the most common NHL, is an example of an aggressive NHL that is potentially curable with modern treatment.