Risks, Diagnosis, and Treatment of Non-Hodgkin Lymphoma

Pharmacy Practice in Focus: Health SystemsJuly 2018
Volume 7
Issue 4

Non-Hodgkin’s lymphoma (NHL) was the seventh most prevalent form of cancer in the United States in 2017, according to the National Cancer Institute.

Non-Hodgkin’s lymphoma (NHL) was the seventh most prevalent form of cancer in the United States in 2017, according to the National Cancer Institute. NHL has more than 60 subtypes that are identified by the World Health Organization.1

In 2015, there were about 686,000 Americans living with NHL. The 5-year overall survival rate for patients living with NHL is 71%. Many clinicians who encounter NHL must make complex patient decisions. Therefore, an interdisciplinary team is crucial to managing this disease state. There are new therapeutic options, and treatment for NHL has become more promising. Let’s explore NHL in more depth.

Risk Factors

The etiology of NHL is unknown, which is the case with most cancers. However, research has determined several risk factors that can be associated with a greater chance of developing NHL, including demographics, environmental and therapeutic agents, genetic factors, and immune status.

Demographics that show a strong association with NHL can first be explained by age. The average patient who is diagnosed with NHL is 67,1 and it is more common to see NHL in the elderly population. However, NHL can occur at any age.2 In addition, more men than women have NHL and Caucasians have a higher risk of NHL than do African Americans, Asian Americans, or Latinos.2

Immune status is the most crucial risk factor for NHL. Table 1 lists risk factors that are associated with immunocompromised patients.2

Environmental agents and therapeutic agents known to suppress the immune system are risk factors for NHL.2 Immunosuppressive drugs, such as those used for chemotherapy and radiotherapy, solid organ transplant agents, and tumor necrosis factor—alpha inhibitors are strong agents that act against the immune system. Some environmental agents, such as those seen in herbicides and insecticides, are risk factors as well.3

Genetics are another risk factor in NHL. Single nucleotide polymorphisms and first-degree relatives have an increased risk of NHL. There are common additions, deletions, and genetic mutations that have been seen. Chromosomal translocations have become a major risk factor, too.


The lymph system is part of the immune system. Its function is to help ward off diseases and infections and enable fluid movement throughout the body.4 NHL is a cancer that originates within lymphocytes, a type of white blood cells. The 2 main cells of origin seen in NHL are T cells and B cells.

Lymphomas can be classified not just by cell origin but also by lymphoma subtype. Table 2 portrays the 2 main subtypes of lymphoma: Hodgkin’s lymphoma and NHL.4

NHL can be further classified into subtype: such as Burkitt lymphoma, chronic lymphocytic leukemia, diffuse large B-cell lymphoma (DLBCL), extranodal marginal zone lymphoma, follicular lymphoma, lymphoblastic lymphoma, mantle cell lymphoma, small lymphocytic leukemia, and splenic marginal zone lymphoma. It can also be classified as aggressive or indolent. Aggressive is fast growing and accounts for 60% of NHL. Indolent lymphomas are slow-growing and have fewer symptoms when diagnosed.5

Because NHL is a cancer subtype, there is a strong hypothesis for the role of oncogenes in its complex pathophysiology. There are proto-oncogenes and tumor suppressive genes found in patients with NHL. Several theories surround these chromosome translocations. There may be a loss of chromosome 6 (6q), BCL6 mutations, chromosomal rearrangements, or a class switch between heavy chain IgM to IgA, IgE, or IgG. There may also be a somatic hypermutation (SHM) which is mostly seen in aggressive or transformed NHL. Hypermutation is a major factor in lymphomagenesis. B cell genes can undergo SHM, while T cell genes cannot.5


Symptomatology plays a role in the diagnosis of NHL. The B symptom triad includes fever, nocturnal sweats, and unexplained weight loss greater than 10% within the past 6 months. Forty percent of patients may experience B symptoms. Patients may also present with fatigue and lymphadenopathy, which can be localized or lead to organ dysfunction. A correct diagnosis requires a lymph node biopsy of the entire lymph node. Because NHL can spread to the bone marrow, patients may require a bone marrow biopsy as well. And a computed topography scan or lumbar puncture is necessary if there is suspected central nervous system (CNS) involvement.5


The prognosis can vary by stage and type of lymphoma, as well as patient-specific factors. Past and present illnesses of the patient, as well as any symptoms, contribute to the prognosis. T-cell lymphomas have a poorer prognosis than B-cell NHL.

There are common prognosis tools that many clinicians can use, such as the International Prognostic Index (IPI) for DLBCL and Follicular Lymphoma International Prognostic Index (FLIPI). Table 3 shows the approaches to specific NHL subtypes.6


Treatment depends on certain criteria, such as the extent of disease. There are 3 main approaches to treatment: chemotherapy, immunotherapy, and radiation therapy. Chemotherapeutic agents are usually dosed by body surface area. Table 4 shows the necessary lab values that must be obtained from patients before initiating treatment.7 Table 5 includes common treatment approaches that are used in NHL.7

DLBCL indicates diffuse large B-cell lymphoma; NHL, non-Hodgin’s lymphoma; MCL, mantle cell lymphoma; and mABs, monoclonal antibodies.

For patients with aggressive lymphomas, regular follow-up visits with their oncologist are recommended up to 3 years post treatment. Indolent and slow-growing lymphomas require frequent follow-up and monitoring throughout a patient’s lifetime.7


There are many complications associated with NHL treatment that can be emotionally overwhelming and financially draining. NHL can become refractory, a state in which therapy doesn’t work for the patient or the disease becomes recurrent.

Also, treatment for NHL can cause many complications that include, but are not limited to, cardiomyopathy, endocrine dysfunction, infertility, neurological dysfunction, and secondary malignancy. Organs, such as the bones, liver, and lungs can be affected. For example, if patients are taking anthracycline, they should have their cardiac function monitored, and if they are taking bleomycin, they should have pulmonary function test monitoring. Many agents are contraindicated in pregnancies, and therefore pregnancies must be ruled out to minimize complications. Table 6 shows potential complications from chemotherapeutic agents.7

Prevention of nausea and vomiting is very important with chemotherapy. Table 7 shows common agents that are used in oncology clinical practices.8


There are new advances in treating NHL that can be anticipated with additional research approaches and technological development. In 2018, about 75,000 new cases of NHL will be diagnosed, and an estimated 19,910 individuals will succumb to this disease.9 Clinicians can assist with pharmacotherapy and symptom management and be vital members of the interdisciplinary team.9 They should develop a relationship with patients and their families. Patients should feel security, support, and trust from their interdisciplinary health care team members.

Jerry Barbee Jr, PharmD, BCPS, CPh, and Glenn Schulman, PharmD, MS, BCPS, BCACP, BCGP, are clinical pharmacists at HCA West Florida Hospital in Pensacola. Jasmin Tawfic is a PharmD candidate at the University of Florida.


  • Cancer stat facts: non-Hodgkin lymphoma. National Cancer Institute website. seer.cancer.gov/statfacts/html/nhl.html. Accessed June 19, 2018.
  • Non-Hodgkin’s lymphoma.” MD Anderson Cancer Center website. mdanderson.org/cancer-types/non-hodgkins-lymphoma.html. Accessed June 19, 2018.
  • Krishnan B, Morgan G. Non-Hodgkin lymphoma secondary to cancer chemotherapy. Cancer Epidemiol Biomarkers Prev. 2007;16(3):377-380.
  • Lee D. Lymphoma. SlidePlayer. .www.slideplayer.com/slide/12262113/. Accessed June 19, 2018.
  • Freedman AS, Friedberg JW, Aster JC. Clinical presentation and diagnosis of non-Hodgkin lymphoma. UpToDate wbsite. uptodate.com/contents/clinical-presentation-and-diagnosis-of-non-hodgkin-lymphoma?search=non%2Bhodgkins%2Blymphoma&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed June 19, 2018.
  • Chan A, Yee GC. Lymphomas. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. AccessPharmacy. 9th ed. New York, NY: McGraw-Hill Education; 2014.
  • Lymphoma - non-Hodgkin: latest research.” Cancer.net website. cancer.net/cancer-types/lymphoma-non-hodgkin/latest-research. Published December 20, 2016. Accessed June 19, 2018.
  • Jordan K, Sippel C, Schmoll H. Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations. Oncologist. 2007;12(9):1143-1150.
  • American Cancer Society. Key statistics for non-Hodgkin lymphoma. ACS website. cancer.org/cancer/non-hodgkin-lymphoma/about/key-statistics.html. Updated January 4, 2018. Accessed June 19, 2018.

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