All About Pediatric Non-Hodgkin Lymphoma
What is lymphoma?
In general, lymphoma is a type of cancer affecting cells of the lymph system. The lymph system is part of the immune system that consists of a network of lymph nodes, lymph vessels, and organs, including the thymus, spleen, and bone marrow. Lymphoma can arise from any of these tissues. There are two broad categories of lymphoma: non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma, which is discussed in a separate article. The cancerous cell in NHL is called a "lymphocyte", which is a cell that ordinarily is involved in the immune response that protects the body from infection. In NHL, these lymphocytes divide at an abnormally fast rate causing enlargement of lymph nodes or other organs in the lymph system and are responsible for the symptoms experienced by children with NHL.
Who is at risk for NHL?
As with most childhood cancers, the majority of pediatric cases of NHL occur in patients without specific risk factors, or "sporadically". In the absence of risk factors, NHL tends to affect adolescent and young adult patients more than young children. In a small minority of cases, NHL occurs in patients who have a predisposing condition or risk factor for developing this specific form of cancer. The most common risk factor in pediatric patients is immunodeficiency, because of either an inherited or acquired condition affecting the immune system. A variety of inherited immunodeficiencies can predispose to developing NHL, but all are rare conditions. Acquired immunodeficiencies can occur when children require medications that suppress certain immune cells, such as after receiving a solid organ transplant (e.g. kidney, liver, heart, lung) to prevent graft rejection, or in the case of viruses such as HIV.
What are the symptoms of NHL?
Children can experience a very wide range of symptoms when affected by NHL, depending on where in the body the lymphoma cells are present. Some common symptoms that should be reported to a healthcare provider include:
- Enlarged lymph nodes in the neck, underarm, or groin (usually painless and firm)
- Enlarged spleen or liver. With an enlarged spleen, your child may feel full or have pain in the upper left side of the abdomen or back. An enlarged liver may cause symptoms like jaundice (the skin and whites of eyes appear yellow and urine may be darker in color), feeling full and fatigue.
- Difficulty breathing or cough (from an enlarged thymus—an immune organ in the upper chest, or enlarged lymph nodes within the chest)
- Unexplained fevers, unintentional weight loss, or sweating profusely at night
- Vomiting or abdominal pain—caused by obstruction from enlarged lymph nodes in the intestines
How is NHL diagnosed?
When a child has symptoms that suggest a diagnosis of NHL, a healthcare provider will conduct a history and physical examination. While the usual next step in the evaluation is to obtain basic laboratory and imaging tests, these do not provide a definite diagnosis. Findings from this initial evaluation help to determine how and where to obtain a tissue sample, or biopsy, which is necessary in order to definitively diagnose NHL. If an enlarged lymph node is present, this will be removed and examined, under a microscope, by a pathologist. If special tests need to be conducted on the biopsy it may take several days or longer to confirm a diagnosis of NHL.
NHL is categorized based on the specific type of lymphocyte that has become cancerous, and its stage of maturation. Each type of NHL behaves somewhat differently in response to therapy, and knowing the specific subtype allows more precise treatment approaches. In general, the types of NHL that affect children divide rapidly and are considered aggressive. This makes them very amenable to treatment because chemotherapy works by killing rapidly dividing cells. The following are the major types of NHL seen in pediatric patients:
- Burkitt lymphoma
- Diffuse large B cell lymphoma (DLBCL)
- Anaplastic large cell lymphoma
- Lymphoblastic lymphoma (either T- or B-cell)
There are many other types of NHL, but most of these are seen primarily in adults and rarely affect children.
How is NHL staged?
Once the diagnosis of NHL is established, the oncology team will conduct a staging evaluation. In general, patients with NHL will undergo the following tests to determine where else in the body NHL cells may be and to test how well other organs in the body are working:
- Laboratory evaluation of blood counts, electrolytes & kidney/liver function
- CT scan of neck, chest, abdomen, and pelvis
- Positron emission tomography (PET) scan—a type of CT that identifies areas in the body with a high metabolic rate, like cancer
- Bone marrow biopsy
- Cerebrospinal fluid sampling by lumbar puncture (spinal tap/LP)
This battery of tests will accurately characterize the extent of disease (stage), which will help the oncologist decide what type of treatment is needed, and provide a useful baseline to measure response to treatment in the future. NHL in pediatrics is staged using the St. Jude system:
- Stage I: single site of disease (not in chest or abdomen)
- Stage II: 2 or more lymph node groups on same side of diaphragm
- Stage III: 2 or more lymph node groups on opposite sides of the diaphragm; or any chest tumor or tumor near the spinal cord
- Stage IV: involvement of the spinal fluid and/or bone marrow
How is NHL treated?
Knowing the specific subtype of NHL and the staging information is critical for formulating an effective treatment plan. In general, this information is obtained prior to initiating any therapy. In situations where the cancer is the cause of a medical emergency, however, urgent treatment may begin prior to having all the necessary information. Examples of such emergencies include times when the lymphoma is threatening the function of a vital organ or structure such as the heart, airway, spinal cord, or kidneys, or when the rapidly dividing lymphoma cells are causing serious disturbances in the electrolyte balances in the body. These situations are relatively uncommon.
Because the vast majority of NHLs affecting children are composed of rapidly dividing and aggressive lymphoma cells, chemotherapy is a very effective treatment modality for pediatric NHL. Often, chemotherapy is the only treatment needed. The type of chemotherapy depends on the subtype of NHL and the extent of disease (staging), and varies both in terms of the intensity and duration of treatment. In all cases, combinations of drugs are used to attack the lymphoma in multiple different ways.
For Burkitt lymphoma and DLBCL, treatment tends to be short (lasting 3-6 months) but intensive, often requiring admission to the hospital. Anaplastic large cell lymphoma therapy is somewhat longer (up to 1 year) but the therapy is less intense and can often be given on an outpatient basis. Finally, lymphoblastic lymphomas are treated mostly as outpatients over approximately 2 years. Since the style and duration of chemotherapy differ dramatically based on the subtype of NHL, it is difficult to generalize what specific chemotherapy agents are used; however, some of the more common medications used (in combination) to treat pediatric NHL are:
- Steroids (prednisone, prednisolone, dexamethasone)
- Cytarabine (Ara-c)
Depending on the subtype of NHL and whether the lymphoma is present in the cerebrospinal fluid, chemotherapy may be administered directly into the spinal fluid during a lumbar puncture. This is called intrathecal chemotherapy. It is given in conjunction with standard chemotherapy, even when lymphoma cells are not seen in the spinal fluid during the initial staging evaluation. Intrathecal chemotherapy is used preventatively to decrease the risk of the lymphoma coming back in the central nervous system.
One of the most important aspects of the treatment process is monitoring the individual patient's response. While we know what medicines work for most children with NHL, currently we cannot predict with complete certainty which lymphomas will respond. During treatment, the oncology team will get imaging tests (mostly CT scans and sometimes PET scans) to evaluate how well the lymphoma is responding. If the response is slow or not complete, changes to the treatment plan may be made to see if alternative chemotherapy agents will be effective.
What if NHL comes back after treatment?
After therapy is over, children who have been treated for NHL are monitored every several months with labs, imaging tests, and physical examinations to determine if the lymphoma is coming back (relapsing). The highest risk for relapse is in the first two years after the end of treatment, but can occur later. Relapsed NHL can be more difficult to treat and get to remission than initial NHL, and typically involves more intensive therapy—often with different medications than those used initially. If another remission is achieved, many patients will require a bone marrow transplant and radiation to optimize their chance of cure. The bone marrow transplant will either use the patient's own cells to help them recover from very high doses of chemotherapy (autologous transplant) or bone marrow cells from another person (allogeneic transplant). The choice of whether to use bone marrow transplant and which type is appropriate is highly individualized, and depends on the subtype of NHL, the timing of relapse, response to treatment, availability of donors, among many others.
There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.
Follow-up Care and Survivorship
After treatment for childhood cancer, the patient will be followed closely to monitor for the cancer coming back, to help them heal from ongoing side effects, and to help them to transition to survivorship. Initially they will be seen often and have ongoing tests to monitor their health. As time goes on, these visits and testing will become less frequent. The oncology team will discuss each patient’s individual follow up plan with them.
Survivors often wonder what steps they can take to live healthier after cancer. There is no supplement or specific food you can eat to assure good health, but there are things you can do to live healthier, prevent other diseases, detect any subsequent cancers early and work with the social and emotional issues, including insurance, employment, relationships, sexual functioning, and fertility, that a prior cancer diagnosis sometimes brings with it. Your oncology team is there to support you and can help you find support resources.
It is important to have a plan for who will provide your cancer-focused follow up care (an oncologist, survivorship doctor or primary care doctor). Talk with your oncology team about developing a survivorship care plan. If you would like to find a survivorship doctor to review your history and provide recommendations, you can contact cancer centers in your area to see if they have a survivor's clinic or search for a clinic on OncoLink's survivorship clinic list.