A Close Look at Lymphoma

By Karen Appold

Lymphoma is a cancer of the cells of the lymphatic system, which is composed of tissues and organs that produce, store, and carry white blood cells that fight infections and other diseases. The lymphatic system contains lymphoid tissue, which is made up of lymph cells, called lymphocytes. The two main types of lymphocytes are B-cells and T-cells. There are B-cell lymphomas (about 85 percent) and T-cell lymphomas (about 15 percent). The most frequent locations for lymphoma development—the lymph nodes, liver, spleen, and bone marrow—all contain large amounts of lymphoid tissue.

Lymphoma comprises more than 67 subtypes of two closely related cancers: non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma,1 named for Thomas Hodgkin, an English physician who described the disease in 1832.

More than 600,000 Americans have lymphoma.2 In 2010 an estimated 74,030 people in the United States were expected to be diagnosed with lymphoma (65,540 cases of NHL and 8,490 cases of Hodgkin’s lymphoma). That same year 21,530 persons were expected to die of lymphoma (20,210 from NHL and 1,320 from Hodgkin’s lymphoma).1 Since 1997 death rates for NHL have decreased by 3 percent annually in men and by 3.7 percent annually in women.3

The seventh most common form of cancer, NHL ranges from indolent (slow growing) to highly aggressive (fast growing). Risk increases with age. “While indolent NHL is not curable (unless it is localized to one or two lymph node regions), some patients live for many years,” says Daniel Lebovic, MD, a clinical lecturer in the Division of Hematology-Oncology at the University of Michigan.

Hodgkin’s lymphoma represents about 11 percent of lymphomas and presents mostly during adolescence and early adulthood. It often develops in one lymph node region and spreads to neighboring nodes. It is very curable, even in its advanced stages.

Risk Factors and Symptoms

“Little is known about the causes of lymphoma,” says Anas Younes, MD, a professor at the University of Texas MD Anderson Cancer Center’s Department of Lymphoma/Myeloma. Almost all types contain mutations within DNA, and risk factors include older age, exposure to certain chemicals, immune deficiency (due to immunosuppressive drugs, HIV/AIDS, or congenital immune deficiency), certain infections (H. pylori of the stomach and human T-lymphotropic virus), radiation exposure, and possibly some viruses such as Epstein-Barr virus and hepatitis C virus.

Common signs and symptoms of lymphoma are enlarged lymph nodes, low energy, fevers, night sweats, poor appetite, weight loss, pain, profound fatigue, itching, and abnormal routine blood tests.

Making a Diagnosis

“Certain observations may raise the suspicion of lymphoma,” Dr. Lebovic says. A physician may feel enlarged lymph nodes during a routine physical exam, or a computed tomography (CT) or positron emission tomography (PET) scan may show an enlarged liver, spleen, or nodes.

“The most accurate diagnosis is made by biopsying an enlarged node,” says Bruce D. Cheson, MD, FACP, head of hematology and deputy chief of the Division of Hematology-Oncology at Georgetown University Hospital, Lombardi Comprehensive Cancer Center. A biopsy involves surgically removing a small tissue sample. By looking under a microscope, a pathologist can confirm lymphoma as well as the type.

Lymphoma can also present in bone marrow, and in some instances diagnosis is made by bone marrow biopsy.

Treatment Options

There are three broad categories of lymphoma treatment: systemic therapy, radiation therapy, and bone marrow (or stem cell) transplant. Treatments are often combined. A watch and wait approach may be recommended in some cases when a patient has a very slow growing form of lymphoma. “Some indolent lymphomas may not need treatment for months to years,” Dr. Cheson says. “Therefore you watch and wait.”

Systemic therapy Systemic therapy includes chemotherapy, immunotherapy, and radioimmunotherapy. These modalities are the mainstay of treatment for almost all lymphoma subtypes.

Chemotherapy, a drug or combination of drugs administered intravenously, kills cancer cells and remains an integral component of treatment. “The more aggressive the lymphoma, the more intense the chemotherapy drugs will be,” Dr. Lebovic notes. Chemotherapy is used to treat all Hodgkin’s lymphomas, all aggressive NHLs, and advanced-stage indolent NHLs. “Patients with enough energy to remain relatively independent in their daily activities are much more likely to tolerate chemotherapy,” Dr. Lebovic says.

Immunotherapy is used to fight B-cell NHL by either stimulating a patient’s immune system to work harder or by giving patients manmade versions of immune system components. Rituxan® (rituximab) is the most effective agent to date; it is usually used in combination with chemotherapy. Immunotherapy, which is less toxic than typical treatments, seems most effective for treating smaller, early-stage cancers.4

Radioimmunotherapy delivers radiation therapy directly to tumor sites. Radioimmunotherapy agents are therapies like Rituxan, which have a radioisotope attached to them. These “guided missiles” are able to destroy cancer cells because they attach to the lymphoma and deliver small doses of medicine to the cells.5

A treatment for advanced-stage indolent B-cell NHL, radioimmunotherapy is used as a single agent and requires only one treatment.

Radiation therapy Radiation therapy is occasionally used as an adjunct to chemotherapy, as it destroys localized lymphoma cells that may have survived chemotherapy by damaging their DNA. Radiation is also an alternative for patients who cannot tolerate chemotherapy, and it can be used to manage pain or swelling. “Essentially, any lymphoma patient can benefit from radiation,” Dr. Lebovic says.

Bone Marrow (or Stem Cell) Transplant

High-dose chemotherapy and a blood stem cell, or bone marrow, transplant is the best treatment available for certain lymphomas. Higher doses of chemotherapy (known as dose-intensive or high-dose therapy) kill more cancer cells than do lower doses in certain types of cancer. These higher doses also damage normal cells, however, particularly the blood-producing stem cells in the bone marrow.

To help bone marrow make healthy new blood cells, some stem cells (early, blood-forming cells that grow and mature in the bone marrow but can circulate in the blood) may be extracted before chemotherapy is given. These cells are then transplanted back into the body, where they restore bone marrow so that it can build healthy new blood cells.5

Stem cell transplants are classified based on which individual donates the stem cells and the source from which they are collected (bone marrow, peripheral blood, or umbilical cord). Each of these variables presents important advantages and disadvantages.

When the stem cells come from the patient, the transplant is referred to as an autologous transplant. This type is recommended for patients with aggressive lymphoma who initially responded to chemotherapy but relapsed after their first-line regimen. Because a transplant is most successful when it’s performed with as little active lymphoma as possible, patients receive two or three additional chemotherapy cycles prior to transplant. Autologous transplants are generally performed only in patients in relatively good health (aside from their lymphoma) who are under 70 years of age.

In an allogeneic transplant, the patient receives bone marrow cells from a bone marrow donor (someone with certain immune system similarities), often a sibling. Ideally, the donor bone marrow cells view the cancer as “foreign” and attack it. In some cases, however, the donor bone marrow cells view some of the patient’s normal tissue as foreign and attack them, a response called graft versus host disease. Allogeneic transplants contain far greater risks and are generally reserved for patients younger than 65.

An allogeneic transplant can benefit patients who relapse after an autologous transplant or who cannot receive an autologous transplant because their disease is not sensitive to chemotherapy.

When the donor is an identical twin, it is referred to as a syngeneic transplant.

Side Effects of Lymphoma Treatment

General side effects of chemotherapy include fatigue, nausea, hair loss, decreased appetite, peripheral neuropathy (tingling in hands and feet), decreased blood counts, and suppression of the immune system, which can lead to increased risk of infection.

Advances in supportive care therapies, created to help alleviate these symptoms, have made chemotherapy much more tolerable in recent years. Nausea, for example, can be managed with preventive antinausea medications delivered before and after chemotherapy. Treatments are also available to help boost decreased blood counts, though in some cases patients may need blood and/or platelet transfusions.

The immunotherapy agent Rituxan must be carefully administered, Dr. Lebovic notes, “because after the first treatment many patients develop chills, shakes, fevers, low blood pressure, and difficulty breathing if it is infused too quickly.”

Patients who receive radioimmunotherapy may experience mild nausea, fatigue, and a moderate lowering of blood counts.

Side effects of radiation depend on the region of the body being treated. They range from very mild reactions, like superficial skin irritation, to more-severe reactions like mouth sores, difficulty swallowing (when the neck is radiated), and nausea or diarrhea (when the abdomen or pelvis is radiated).

Patients undergoing stem cell transplantation experience side effects similar to those of chemotherapy treatment because they receive high-dose chemotherapy as part of this treatment. Side effects for autologous transplants last up to 14 days, whereas allogeneic transplant side effects present up to 30 days. To reduce the chance of graft versus host disease, allogeneic transplant patients may receive immunosuppressive drugs for more than one year.

The Recovery Process

“Once lymphoma patients are in remission, they have laboratory testing and CT or PET scans every three to six months, followed by an oncologist visit,” says Dr. Cheson.

Generally, the more aggressive the lymphoma, the shorter the period between remission and relapse. For that reason, Dr. Lebovic says, “patients with aggressive lymphomas who achieve remission are followed closely for the first couple of years, but then the intensity of monitoring declines.” Patients with indolent lymphomas are followed less frequently, Dr. Lebovic says, though with similar intensity.

The five-year survival for Hodgkin’s lymphoma patients is approximately 85 percent, whereas the 10-year rate is 81 percent. The five-year survival for NHL patients is approximately 67 percent, and the 10-year rate is 56 percent.2


1. Jaffe ES, Harris NL, Stein H, Isaacson PG. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood. 2008;112(12):4384-99.

2. Altekruse SF, Kosary CL, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2007. National Cancer Institute website. Available at: http://seer.cancer.gov/csr/1975_2007. Accessed April 7, 2011.

3. Cancer Facts & Figures 2010. American Cancer Society website. Available at: http://ww2.cancer.org/downloads/STT/Cancer_Facts_and_Figures_2010.pdf. Accessed April 7, 2011.

4. Immunotherapy. American Cancer Society website. Available at: http://www.cancer.org/Treatment/TreatmentsandSideEffects/TreatmentTypes/Immunotherapy/immunotherapy-what-is-immunotherapy. Accessed April 7, 2011.

5. Lymphoma Treatments. Lymphoma Research Foundation website. Available at: http://www.lymphoma.org/site/apps/s/content.asp?c=bkLTKaOQLmK8E&b=6298135&ct=8806721. Accessed April 7, 2011

Coping with Lymphoma: A Personal Story

Maryann Larson

In January 2009, Maryann Larson felt a painless swollen lymph node in her neck. After multiple visits with doctors and extensive testing, the 59-year-old from Ramsey, Michigan, learned in March of that year that test results showed abnormal cells that looked to be lymphoma.

“I never felt such fear and despair,” Maryann recalls. “I was afraid that I would die soon. Everyone found it hard to believe because I exercise routinely, eat healthily, and embrace wellness and preventive health screening.”

Maryann was diagnosed with non-Hodgkin’s follicular lymphoma, Stage IIIA, grade 1/2, at Northwestern University Medical Center in Chicago, Illinois. She had numerous malignant tumors, including a large tumor mass in her abdomen, and began a treatment regimen that included eight treatments—every three weeks—of Rituxan® (rituximab) chemotherapy. “I tolerated the treatments well,” Maryann says. “I received Benadryl® [diphenhydramine] intravenously, which put me in a twilight sleep.”

Maryann found strength through CancerConnect.com, an online network that encourages cancer patients and caregivers to link with others facing similar issues. “It was comforting to be able to ask others about their experiences,” she says. She also started a blog to keep friends and family updated. “I wept as I read each expression of love and encouragement,” Maryann continues. “Each time I had a treatment, I felt that I was carried in by my cheerleaders.”

Maryann was thrilled to achieve complete remission in October 2009. She will continue receiving Rituxan every three months until September 2011.

“I was advised to think of lymphoma as a chronic disease,” Maryann says. “When it flares up, I’m treated, and then I continue with life. This way of thinking has helped me greatly.”

Advances in Lymphoma Treatment

Rapid therapeutic advances in lymphoma continue at a gratifying pace, leading to important new treatment options for many patients. “Among these are new applications of existing medications, including very durable disease control for indolent non-Hodgkin’s lymphomas [NHLs] with maintenance therapy using the monoclonal antibody—a manmade protein that can bind to lymphoma cells—Rituxan® [rituximab], and the high response rates and lower toxicity of the chemotherapy agent Treanda® [bendamustine] for newly diagnosed and relapsed lymphoma,” says Michael E. Williams, MD, Byrd S. Leavell professor of medicine and the chief of the Hematologic Malignancies Section, Hematology/Oncology Division of the University of Virginia Health System. Dr. Williams is also the former Chairman of the Lymphoma Research Foundation’s Mantle Cell Lymphoma Consortium and a member of the Scientific Advisory Board Executive Committee.

“The novel targeted monoclonal antibody brentuximab vedotin (SGN-35) has shown dramatic response in patients with otherwise treatment-resistant Hodgkin’s lymphomas as well as certain NHLs,” Dr. Williams continues. “Additional novel monoclonal antibodies and targeted therapeutics are in the advanced stages of clinical testing, and there is every expectation that these dramatic improvements in outcomes, survival, and cure will continue.”

Here are just some of the therapies that exemplify the advances being made:

  • Brentuximab vedotin (SGN-35) This antibody-drug conjugate is targeted to CD30, a defining marker of Hodgkin’s lymphoma, and is also a target expressed on various T-cell cancers and other hematologic malignancies.1 A type of immunotherapy/chemotherapy, it is administered intravenously.
  • Revlimid® (lenalidomide) This oral immunomodulatory therapy is being evaluated as a single agent for patients with mantle cell lymphoma and T-cell lymphoma, as well as in combination with Rituxan in patients with follicular NHL and following Rituxan plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment in patients with diffuse large B-cell lymphoma.2
  • Rituxan® (rituximab) Studies show that in patients with advanced indolent NHL, maintenance Rituxan (a type of immunotherapy administered intravenously) after chemotherapy significantly prolongs progression-free survival to a far greater extent than has been achieved by any previous strategy and with minimum toxicity.3
  • Treanda® (bendamustine) The simpler two-drug regimen of Treanda plus Rituxan could become the new standard first-line therapy for indolent NHL, in place of the current standard regimen of R-CHOP. A study showed that this chemotherapy regimen improved progression-free survival and complete remission rates while showing a better tolerability.4


1. Brentuximab Vedotin (SGN-35). Seattle Genetics website. Available at: http://www.seagen.com/product_pipeline_sgn35.shtml. Accessed April 7, 2011.

2. Clinical Data from Two Phase II Studies Evaluating Revlimid Plus Rituximab in Indolent Non-Hodgkin’s Lymphomas Presented at ASH. Celgene website. Available at: http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle_pf&ID=1505167. Accessed April 7, 2011.

3. Rituximab Maintenance Improves Progression-Free Survival in Indolent Lymphoma. Medscape Today website. Available at: http://www.medscape.com/viewarticle/589819. Accessed April 7, 2011.

4. Bendamustine Plus Rituximab Could Replace R-CHOP in Indolent Lymphomas. Medscape Today website. Available at: http://www.medscape.com/viewarticle/713573. Accessed April 7, 2011.

An Alternative Treatment Option: Clinical Trials

Clinical trials are research studies that are conducted to answer questions about a promising treatment or a new way of using an old treatment. Daniel Lebovic, MD, a clinical lecturer in the Division of Hematology-Oncology at the University of Michigan, recommends that patients volunteer for clinical trials if they have a lymphoma subtype that doesn’t have good treatment options or if they haven’t adequately responded to typical treatments.

Patients can learn about clinical trials through their treatment center or through the following organizations: