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Non-Hodgkin Lymphoma and Hodgkin Lymphoma: The Role of the Nurse Navigator in Improving Patient Outcomes

Best Practices in Patient Navigation - First Issue: Lymphoma Edition

Lymphomas are a group of blood cancers that originate in the lymphatic system. The primary function of this system is to help the body fight infection.1 The lymphatic system has 2 major organ groups, the bone marrow and the thymus, which produce B and T lymphocytes, respectively. T lymphocytes (also called T cells) help in cytokine production to fight infections and regulate the immune system. B lymphocytes (also called B cells) help to produce specific antibodies against antigens that are attacking the body. The lymphatic system circulates the lymphocytes throughout the body to protect it against infection.2

Lymphomas occur when lymphocytes change and undergo uncontrolled cell growth, thereby crowding out healthy cells and forming masses and enlarged lymph nodes throughout the body. These changes impact the body’s ability to fight infection and produce healthy cells. The 2 main types of lymphoma are Hodgkin lymphoma (HL) and non-Hodg-kin lymphoma (NHL). NHL can be further divided into more than 60 subtypes, which can be classified as indolent (slow-growing) or aggressive (fast-growing) (Table 1).1

HL is one of the most curable forms of cancer. It occurs when abnormal B cells, called Reed-Sternberg cells, proliferate in the lymphatic system. Reed-Sternberg cells do not respond to normal programmed death signals within the cell. These cells are not present in any other type of lymphoma and do not play a part in the body’s ability to fight infection. HL can be found anywhere in the body, but it usually occurs in the lymph nodes in the upper body. HL can be classified as 2 different types: (1) classical HL, which accounts for approximately 95% of cases, and (2) nodular lymphocyte-predominant HL.2

Epidemiology of Lymphoma

It is estimated that approximately 79,990 new cases of lymphoma will be diagnosed in the United States in 2014. Of those cases, approximately 9190 will be HL and 70,800 will be NHL.3 HL occurs most frequently in adolescents and young adults between the ages of 15 and 35 years and in adults aged 65 years. HL occurs slightly more often in men than women, and the incidence of NHL is much higher in whites than in other racial/ethnic groups.4

Survival rates for lymphoma continue to increase, reflecting the success of new treatment regimens. These rates depend on the type of lymphoma, stage and extent of disease, presence or absence of extranodal disease, and a patient’s age and performance status. For NHL, 1- and 5-year survival rates are 81% and 69%, respectively. Survival rates decline to 58% by 10 years after diagnosis.3 HL, on the other hand, has a more favorable prognosis. The 1-, 5-, and 10-year survival rates for HL are 92%, 85%, and 80%, respectively.3

Risk Factors for Lymphoma

For most individuals, the cause of lymphoma is unknown. However, certain risk factors that alter the immune system are thought to play a role in the development of lymphoma (Table 2).5 Other risk factors include environmental exposure to high-dose radiation, pesticides, herbicides, benzenes, or hair dyes made before 1980.5 Individuals with certain occupations may also be at higher risk for developing lymphoma, such as farmers, chemists, petroleum workers, and those who work in the rubber, plastic, and synthetics industries.6

Genetic predispositions account for a small percentage of lymphomas. People with a family history of HL may have a slightly increased risk of developing the disease. Patients who have undergone an organ transplant and are on immunosuppressive drugs are also at increased risk for  developing the disease.6

Signs and Symptoms of Lymphoma

The most common sign of NHL is the presence of enlarged lymph nodes anywhere in the body. Other signs and symptoms include fatigue, fever, night sweats, generalized itching, unexplained weight loss, decreased appetite, coughing, dyspnea, chest pain, and abdominal pain or a feeling of fullness in the abdomen.7

The most common signs and symptoms of HL are swollen lymph nodes, fever, night sweats, fatigue, pruritus, and weight loss. Some patients may be sensitive to alcohol or have painful lymph nodes after drinking alcohol. Patients may experience other symptoms, such as dyspnea and coughing, if lymph nodes in the chest are involved. However, it is important to note that some patients with lymphoma do not experience any symptoms.2

Diagnosis and Workup of Lymphoma

When a patient is suspected of having lymphoma, a complete health history is taken and a physical examination is performed, followed by a number of diagnostic tests. A biopsy of the enlarged lymph nodes or organ is necessary to determine whether lymphoma is present. There are several types of biopsies that can be performed to obtain tissue, including fine needle aspiration, core needle biopsy, and surgical biopsy. The choice is made by the oncology team and is often based on the location of the enlarged lymph nodes.8

Determining the specific makeup of the lymphoma is essential for selecting appropriate treatment. Immunophenotyping is performed on the tissue biopsy sample to determine the exact type of lymphoma. Cytogenetic testing is also necessary to determine whether chromosomal abnormalities are present. Gene expression and microarray analysis can help to determine how patients will respond to treatment and their risk of relapse. It is especially effective in distinguishing between different forms of diffuse large B-cell lymphoma. Bone marrow biopsy is also important to determine whether the disease has metastasized to the bone.7

Additional tests conducted as part of the workup for lymphoma may include a complete blood count, ultrasound, computed tomography scan, magnetic resonance imaging, or positron emission tomography scan.7


NHL is staged based on the Ann Arbor staging system, which is used to summarize the extent of the disease8:

• Stage I: The cancer is located in a single region, usually 1 lymph node and the surrounding area. Stage I will often not have obvious, outward symptoms.

• Stage II: The cancer is located in 2 separate lymph node regions, and both regions are on the same side of the diaphragm (either above or below the diaphragm).

• Stage III: The cancer involves lymph nodes or organs on both sides of the diaphragm (both above and below the diaphragm).

• Stage IV:

    o The cancer has spread to multiple spots of an organ (or multiple organs) outside the lymph system. Cancer cells may or may not be found in the lymph nodes near these organs.


    o The cancer has spread to only 1 organ outside the lymph system, but lymph nodes far away from that organ are involved.


    o There is bone marrow involvement.

The staging of HL is based on the Cotswold system, a modification of the Ann Arbor system9:

• Stage I: The cancer is found in only 1 lymph node area or lymphoid organ such as the thymus (stage I), or the cancer is found in only 1 area of a single organ outside the lymph system (stage IE).

• Stage II: The cancer is found in 2 or more lymph node areas on the same side of the diaphragm (stage II), or the cancer extends locally from one lymph node area into a nearby organ (stage IIE).

• Stage III:

    o  The cancer is found in lymph node areas on both sides of the diaphragm (stage III).


     o The cancer is in lymph nodes both above and below the diaphragm, and it has also spread to a nearby organ (stage IIIE), to the spleen (stage IIIS), or to both (stage IIIES).

• Stage IV:

    o The cancer has spread widely through 1 or more organs outside the lymph system. Cancer cells may or may not be found in nearby lymph nodes.


    o The cancer is found in organs in 2 distant parts of the body (and not in nearby lymph nodes).


    o The cancer is in the liver, bone marrow, lungs (other than by growing there directly from another site), or cerebrospinal fluid.

In both NHL and HL, one of the following letters can be added to the stage to provide further detail (eg, stage IIA, stage IIIB)8:

    A: The patient has no symptoms.

    B: The patient has one or more “B symptoms”: loss of more than 10% of body weight over the previous 6 months (without dieting), unexplained fever of at least 100.4°F (38°C), or drenching night sweats.

    E: The disease is “extranodal” (not in the lymph nodes) or has spread from lymph nodes to adjacent tissue.

    X: The largest tumor is larger than 10 cm (also called “bulky disease”), or the lymph node mass in the center of the chest (mediastinum) is wider than one-third of the chest on a chest X-ray.

Treatment of Lymphoma

Overview of Management Strategies for NHL

For the more aggressive types of NHL, treatment usually includes some combination of chemotherapy, biologic therapy, radiation therapy, and immunotherapy, and perhaps also a stem cell transplant. Treatment decisions are based on the type of NHL, the stage and grade of disease, and comorbidities, among other patient- and disease-related factors.7

Indolent or low-grade NHL is often simply observed, not treated. However, radiation may be used for local control of the disease. It should be noted that relapses can occur many years after radiation therapy.7

In general, chemotherapy is the most commonly used treatment for patients with NHL. Chemotherapy works systemically to kill the circulating lymphoma cells. There are many chemotherapy regimens that can be used for the treatment of NHL, depending on patient and tumor characteristics. Radiation therapy is able to treat only limited areas of the body, and it is typically used after chemotherapy. Radiation therapy can also be used for palliation of symptoms related to the lymphoma such as enlarged lymph nodes or spinal cord compression that is causing pain or discomfort.7

Immunotherapy is treatment that either boosts the patient’s own immune system or uses man-made versions of the normal parts of the immune system. This form of treatment is often delivered as biologic therapies, such as monoclonal antibodies, which target specific markers on lymphoma cells. Antibodies are normally produced in the body to attack abnormalities that may occur, such as cancer cells, viruses, and bacterial infections. Monoclonal antibodies are designed to stimulate the patient’s immune system to attack specific cell types and kill the cancer cells. Interferon-alpha is one type of immunotherapy that works by targeting certain receptors on the cancer cells, interfering with cell replication and causing the immune system to attack the cells. Interferon-alpha is used in follicular and cutaneous T-cell lymphomas.10,11

The goal of therapy for patients with NHL is to cure the disease. However, many patients relapse and need additional treatments such as stem cell transplants. Throughout cancer care, there should be discussions between the patient and the oncology team as to which treatment modalities will offer the best outcome.

Overview of Management Strategies for HL

Treatment for patients with HL is based on type (classical or nodular lymphocyte-predominant), patient age and presentation, stage, presence of “B” symptoms, and size of tumor (>4 in or <4 in wide).

The most common treatment for patients with HL is chemotherapy given with radiation therapy. As with NHL, there are many chemotherapy regimens that can be used. Radiation therapy targets localized disease where there are large concentrations of cancer cells.2 HL is treated by either standard photon radiation therapy or proton therapy. Proton therapy is a newer form of radiation therapy whereby proton beams enter the body and stop at the site of treatment, decreasing the toxicities related to therapy. In standard photon radiation therapy, the beams continue through the treated area. The use of proton therapy in HL is still new, so patients should discuss with their cancer care team whether it could be part of their treatment plan.4,12,13

Alternatively, as in the treatment of patients with NHL, radiation therapy may be used alone to treat limited areas of disease or for palliation of symptoms related to the lymphoma. Some biologic therapies are also now being used in HL.4

Stem Cell Transplantation

Patients with NHL or HL may receive a stem cell transplant even if they have undergone chemotherapy, biologic therapy, or radiation therapy. A stem cell transplant may be considered necessary when the disease has recurred after frontline treatment. There are 2 basic types of transplants that can be performed for patients with lymphoma:14:

Autologous stem cell transplant: Stem cells are harvested from the patient, stored, and then reinfused after high-dose chemotherapy.

Allogeneic stem cell transplant: Stem cells from a donor are harvested and infused into the patient after high-dose chemotherapy. The donor must have the same type of immune system as the recipient, and the donor cells are tested to ensure a match with the patient’s cells. A laboratory technician examines the surface of the sample tissue cells to identify the proteins that give everyone his or her own unique tissue type, called human leukocyte antigens (HLAs). If the HLA on the donor cells are identical (eg, from identical twins) or similar (such as those from a sibling), the transplant is more likely to be successful. However, only 1 patient in 4 who could benefit from allogeneic transplant has this ideal donor. If the cells from a relative do not provide a match, cells from an unrelated donor may be found in the general public through a national registry. This is sometimes called a matched unrelated donor transplant.14

Many factors come into play as to which type of transplant is best for a specific patient, and these factors need to be carefully discussed with the oncology team.

Side Effects of Treatment

Chemotherapy is designed to target cancer cells; however, it can also damage healthy cells, resulting in an array of hematologic and nonhematologic toxicities and other complications that can range from mild to severe. These side effects include myelosuppression, chemotherapy- induced nausea and vomiting (CINV), mucositis, fatigue, infertility, and graft-versus-host disease (GVHD).

Myelosuppression is a decrease in the patient’s healthy blood cells. There are 3 basic types of myelosuppression that may occur as a result of treatment15:

Anemia (low number of red blood cells, resulting in low hemoglobin) can cause shortness of breath, tachycardia, or fatigue. Patients may need blood transfusions or hematopoietic growth factors to manage their anemia. These growth factors are usually given subcutaneously on a weekly basis to stimulate the production of red blood cells in the bone marrow.

Thrombocytopenia (low platelet count) puts patients at risk of bleeding or bruising, and they may require platelet transfusions to maintain an adequate platelet count.

Neutropenia (low white blood cell count) puts the patient at increased risk of infection. Patients may experience fever or chills and will need to be closely monitored and treated if fever arises. Lymphoma patients often receive myeloid growth factors as part of their treatment regimen. These drugs help to stimulate the bone marrow to make more white blood cells. These drugs are given subcutaneously with each dose of chemotherapy to help increase white blood cell counts, thereby lowering the risk of infection.

CINV can be one of the most significant toxicities associated with cancer treatment, affecting numerous aspects of a patient’s quality of life and potentially altering the course of therapy. Fortunately, increasingly effective antiemetic agents and combinations are expanding clinical treatment options for patients undergoing chemotherapy. The key to minimizing CINV is prevention, as well as adequate protection throughout the course of therapy. Patients should also be encouraged to meet with a dietitian so that they can receive guidance for maintaining nutrition while undergoing chemotherapy. Other integrative therapies may also be helpful in managing CINV. These include self-hypnosis, reiki, massage therapy, acupuncture, or acupressure.16,17

Mucositis occurs when the lining of the gastrointestinal tract is destroyed as a result of therapy. The patient may experience sores in the mouth or gastrointestinal tract that affect the ability to eat, speak, or swallow. There are multiple treatments available to manage mucositis, such as dietary suggestions, salt water rinses, or prescription medications.18

Most patients with cancer feel fatigued sometime during the course of treatment. The National Comprehensive Cancer Network defines cancer-related fatigue as “a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning.”19 This sense of tiredness is usually not relieved with rest and is not related to an excessive amount of activity. Many patients describe it as feeling “bone tired.” They feel physically, mentally, and emotionally drained. Mild to moderate exercise has been shown to improve fatigue in patients undergoing treatment.19 One intervention that has been proven very effective in large clinical trials to relieve or prevent fatigue is correction of anemia. Other strategies for helping patients manage fatigue include19,20:

Increasing activity: Studies show that patients with cancer who exercise are less tired and depressed. They also sleep better than patients who do not exercise. A referral to physical/occupational therapy can be very helpful in providing practical tips for patients regarding exercise and energy conservation.

Eating well: Many patients experience treatment-related nausea and vomiting as well as decreased appetite. Patients should meet with a nutritionist to discuss tips to ensure that they are getting enough calories, fluids, protein, and other nutrients to help prevent fatigue and increase energy.

Psychosocial support: Activities such as relaxation, counseling, support groups, and biofeedback can decrease fatigue. Therapies that aim to educate patients about fatigue and related factors help reduce fatigue. Sometimes depression and anxiety play a part in symptoms. It is important that these be addressed, as treatment may help in overall fatigue management and improve the patient’s mood.

Rest: It is important to save personal energy. Encouraging patients to ask for help from friends and family allows them to focus on the most important things that need to be done.

Distraction: Patients should try “escaping” from their fatigue by doing things they enjoy. Activities such as reading, watching TV or a funny movie, or doing a craft may help in fatigue management.

Sleep therapy: Many patients with cancer suffer from disrupted sleep patterns. Having a regular sleep/wake pattern will help improve sleep. Using relaxation methods, limiting caffeine to the morning, and keeping naps short will also help.

Patients with lymphoma who undergo treatment may experience infertility. Fertility preservation techniques such as sperm banking and egg preservation should be discussed with patients prior to the initiation of treatment. Because chemotherapy and radiation therapy can cause birth defects, a discussion regarding the use of birth control must occur prior to the start of therapy. Asking patients whether their family is complete is an important question.9

GVHD can occur after allogeneic transplant if the donor’s bone marrow (graft) identifies the recipient’s bone marrow (host) as foreign and therefore attacks the graft tissue. Reactions can be mild to severe and are managed with medications that decrease the immune response. Symptoms of GVHD may include rashes, diarrhea, and mucositis.21

Roles of the Nurse Navigator

A nurse/patient navigator is defined by the Academy of Oncology Nurse & Patient Navigators as “a medical professional whose clinical expertise and training guides patients and their caregivers to make informed decisions, collaborating with a multidisciplinary team to allow for timely cancer screening, diagnosis, treatment, and increased supportive care across the cancer continuum.” Navigators can also provide education to the community regarding cancer risk factors by participating in outreach events.

For a program to be accredited by the American College of Surgeons Commission on Cancer, it must have a navigation process in place.22 That being said, navigation comes in many forms, and each organization has its own model of delivery that works best for the practice or institution.

In general, the barriers that patients face today can be placed in these broad categories: financial, communication, treatment, psychosocial, and logistical23:

• Financial barriers can be related to job loss or decreased time at work, insurance copayments, and other out-of-pocket costs related to appointments and treatment, such as gas, parking, or tolls.

• Navigators play a key role in keeping the lines of communication open between the patient and medical team, as there are often misunderstandings and misconceptions related to the diagnosis and treatment of the disease. The care provided by navigators and the team needs to be patient-centered, at a level the patient understands, and culturally appropriate. Engaging family or friends is common and can aid in making this process smooth.

• Treatment barriers may include compliance challenges related to oral chemotherapies. If patients participate in clinical trials, helping to maintain compliance is an integral part of the navigator role.

• Identifying the patient’s psychosocial situation is important, as patients without a good support system are less likely to complete treatment. It is important that navigators identify the patient’s caregivers, as this will be a stressful time for them as well. Connecting caregivers as well as patients to available resources is an important part of the treatment plan.

• Logistic barriers can be related to the need for lodging or being able to travel to and from treatment centers.

Before Treatment

Nurse navigators can educate patients regarding the diagnostic workup as well as provide support to them through this uncertain time. Patients often have questions about testing, logistical concerns, next steps, and when they can expect results to be in or treatment to start.24

Early intervention by the navigator, if possible, is important for helping newly diagnosed patients access care. This allows the navigator to assess the patient’s needs and identify barriers that may interfere with his or her ability to access, maintain, or complete treatment. For example, when appropriate, navigators can refer the patient to a urologist or OB/GYN who specializes in fertility preservation.23

During Treatment

Once a patient has received a diagnosis of lymphoma, the navigator can develop a plan of care, in conjunction with the oncologist or hematologist, which will help the patient stay on course for treatment. Communication among the healthcare team is essential for providing patient-centered care, and the navigator is often the linchpin in the process that helps keep it all together. Multidisciplinary team huddles are a good way to keep the lines of communication open so that all providers are on the same page regarding the patient’s treatment needs and goals.23

Navigators provide education and support regarding diagnosis, treatment, and supportive care. They assess a patient’s readiness to learn and provide education that is culturally sensitive, in the patient’s native language, and at the proper literacy level. Much of the navigator’s role is to reinforce the plan of care and answer the patient’s questions about treatment, resources, and supportive services. For example, navigators may help patients obtain wigs and hats, advise them about insurance coverage of wigs, and provide support about the emotional impact of hair loss.23

Navigators serve as advocates for patients in supporting their treatment decisions. For some patients, not electing to have treatment is the right choice for them, and navigators can provide resources/referrals to help support that decision. Resources such as palliative care consults, home care, or hospice are helpful in these situations. Collaborating with a social worker throughout treatment can also be beneficial to provide additional psychosocial care.23

A cancer diagnosis may have a big impact on patient and family lifestyle. Navigators play an important role in helping patients identify and achieve their own goals of care during treatment with respect to their personal and family life. Navigators help empower patients with knowledge and education, and encourage them to be an active participant in the team. They can triage concerns, reinforce the care plan, coordinate appointments, and make referrals to other services, such as community organizations, social workers, and counseling.23

After Treatment

The Institute of Medicine has made recommendations regarding survivorship and states that all patients who have completed treatment should be provided an end-of-treatment summary that details the cancer therapy they have received and how it was tolerated.25 This is necessary to help patients transition into the “new normal” of survivorship. The Commission on Cancer has issued a standard that patients must have an end-of-treatment summary in order for a cancer program to be accredited.22

Some side effects of lymphoma therapy may linger for months or years after treatment. Others may not appear until years after treatment ends. The long-term or late effects of cancer treatments can include the risk of developing a second cancer, heart or thyroid problems, infertility, fatigue, depression, hearing loss, an inability to concentrate or focus, or forgetfulness. These latent effects will be individual and depend on many factors, such as treatment type and duration, age, gender, and overall health.23

Navigators need to be aware of and anticipate long-term issues facing patients and be able to provide direction as they transition into survivorship. The navigator can wear many hats in helping patients through the transition process from active treatment to surveillance. These may include reviewing the end-of-treatment summary and providing a survivorship care plan. Other resources that may help patients develop a survivorship plan include LIVESTRONG, OncoLink, and Journey Forward. (See sidebar for additional helpful resources for patients and nurse navigators.)23

Other aspects of survivorship care include helping patients schedule necessary follow-up tests and appointments, and making referrals to psychiatry or counseling, rehabilitation medicine, and primary care providers. It is important to be knowledgeable regarding the resources available for patients, which may include local community resources, copay assistance foundations, pharmaceutical company asssistance programs, nutrition, counseling, integrative therapies, and rehabilitation. Navigators working with patients with lymphoma should be aware of the National Comprehensive Cancer Network consensus guidelines regarding follow-up care.26 Since much of cancer care is provided in the community and by the patient’s primary care physician, it is imperative that navigators help patients establish those connections.23

NHL and HL remain challenges despite recent advances in treatment and supportive care. The goal is to continue to find a cure for these diseases, to improve patients’ quality of life, and to prevent long-term ill effects of therapy. Nurse navigators are an integral part of the healthcare team because they help patients understand their plan of care; provide support, advocacy, and education; and reduce barriers to care. All members of the multidisciplinary team must stay current with new developments in the staging, diagnosis, treatment, and follow-up of lymphoma to improve patient outcomes. Navigators are an important part of this team, as they help patients understand the plan of care and transition through the cancer continuum by providing support, advocacy, and education and reducing barriers to care. 


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17. Nausea and vomiting. OncoLink website. Updated September 18, 2013. Accessed November 28, 2014.

18. Mucositis (mouth sores) and oral care tip sheet. OncoLink website. Accessed November 28, 2014.

19. National Comprehensive Cancer Network. Patient and caregiver resources: fatigue. Accessed November 28, 2014.

20. Puetz TW, Herring MP. Differential effects of exercise on cancer-related fatigue during and following treatment: a meta-analysis. Am J Prev Med. 2012;43:e1-24.

21. Vachani C, Millar LB. Allogeneic transplant (bone marrow and stem cell). Updated August 13, 2010. OncoLink website. http://www.oncolink. org/treatment/article.cfm?c=137&aid=550&id=286. Accessed November 28, 2014.

22. American College of Surgeons, Commission on Cancer. Cancer program standards 2012. Cancer Program Standards 2012: Ensuring Patient-Centered Care. Online January 21, 2014. Accessed November 28, 2014.

23. Blaseg KD, Daugherty P, Gamblin KA. Oncology Nurse Navigation: Delivering Patient-Centered Care Across the Continuum. Pittsburgh, PA: Oncology Nursing Society; 2014.

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25. Hewitt M, Greenfield S, Stovall E. eds. for the Committee on Cancer Survivorship: Improving Care and Quality of Life, Institute of Medicine and National Research Council. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: National Academies Press; 2006.

26. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Survivorship. Accessed January 5, 2015.

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