14 Non-Hodgkin’s Lymphoma

IN THIS CHAPTER YOU’LL DISCOVER

→ What Non-Hodgkin’s Lymphoma Is

→ Non-Hodgkin’s Lymphoma Statistics

→ Types of Non-Hodgkin’s Lymphoma

→ Non-Hodgkin’s Lymphoma Staging

→ Signs and Symptoms

→ Specific Diagnostic Tests

→ Treatments for Non-Hodgkin’s Lymphoma

JOY HUBER WAS 33, single, had just sold her house and was in the middle of packing up to move to Nashville in pursuit of her dream as a songwriter when she was diagnosed with non-Hodgkin’s lymphoma. “Lymph node cancer? Not at 33! I remember standing in my bathroom, looking in the mirror at my reflection, saying, ‘You have cancer. YOU have cancer . . . YOU HAVE CAN-CER!’ But I still could not completely wrap my mind around it,” she recalls.

But, indeed, Huber did have Stage IV follicular lymphoma, a slowly progressing form of non-Hodgkin’s lymphoma that, although treatable, is difficult to cure. She underwent intensive chemotherapy and, now in remission, strives to help others as an author and speaker, spreading awareness.

What Is Non-Hodgkin’s Lymphoma?

Lymph is a clear fluid that circulates through the body via a channel called the lymph system. One of its main functions is to rid the body of toxins as part of our immune defense. Non-Hodgkin’s lymphoma begins when certain cells in the lymphatic system change and begin to grow uncontrollably, which may form a tumor. Non-Hodgkin’s lymphoma is the overall term for a large, diverse group of cancers.

Statistics

Each year, an estimated 70,000 people (37,000 men and 33,000 women) are diagnosed with non-Hodgkin’s lymphoma. Most people develop the disease for no known reason, but growing older heightens risk. The most common forms of non-Hodgkin’s lymphoma occur in those between ages 60 and 70, but people of any age can develop it. The disease is also more common in men.

“Often, when non-Hodgkin’s lymphoma appears in younger people, the course of the disease is more aggressive than in people who are older and usually have the slower growing, indolent types,” says Dr. Alexandra Stefanovic, a hematological oncologist with the Sylvester Comprehensive Cancer Center at the University of Miami. “The number of cases of non-Hodgkin’s lymphoma has been increasing since the 1970s, although it isn’t completely understood why,” Dr. Stefanovic adds.

Factors that affect the immune system can raise the risk for non-Hodgkin’s lymphoma. These include bacterial infections, such as the bacterium Helicobacter pylori, which also causes stomach ulcers. Viruses such as Epstein-Barr that causes mononucleosis, is associated with some types of non-Hodgkin’s lymphoma, as well as hepatitis C.

Immune deficiency disorders, such as HIV/AIDS, greatly hike the risk of this disease. People with autoimmune disorders, such as rheumatoid arthritis and Sjögren’s syndrome, are also at higher risk, although to a far lesser extent. Another high-risk group is people who have undergone organ (kidney, liver, heart, or lung) transplantation, because of the drugs they must take to prevent organ rejection.

There are genetic factors that involve DNA, but they are not of the same types that occur in many other forms of cancer. In some other types of cancer, hereditary factors can play a role, at least in terms of making people more prone to develop the disease if their parents or close relatives are affected. This is not the case with non-Hodgkin’s lymphoma. Although changes in a patient’s DNA do occur, these changes occur after birth. Such acquired changes can occur with exposure to the factors cited above, as well as to radiation and cancer-causing chemicals, like pesticides and petrochemicals, or such mutations can occur for no known reason.

Outcome and Survival Rates

There are about 535,000 non-Hodgkin’s lymphoma survivors in the United States today. This tally includes 280,000 men and 255,000 women.

Non-Hodgkin’s lymphoma is one of the more curable types of cancer. The one-year relative survival rate is 81 percent. The five-year and 10-year relative survival rates are 68 percent and 57 percent, respectively. It is estimated that 19,000 (10,600 men and 8,400 women) deaths from this disease occur each year.

Although there is still work to be done, the cure rate for non-Hodgkin’s lymphoma has risen dramatically over the years. This success stems from an increased understanding of the disease, coupled with the development of better treatments that have improved outcomes. “The five-year survival rate for patients with non-Hodgkin’s lymphoma has probably doubled over the last several years,” says Dr. Patrick Stiff.

One of the factors that revolutionized the treatment of non-Hodgkin’s lymphoma was the development of the drug rituximab (Rituxan), which is a monoclonal antibody that targets a protein found on the surface of immune system B cells and acts to destroy them. Most types of non-Hodgkin’s lymphoma are characterized by an excessive number of B cells, overactive B cells, or dysfunctional B cells.

Another reason why non-Hodgkin’s lymphoma is more easily treated than some other forms of cancer is that lymphomas are generally very sensitive to chemotherapy and radiation and, unlike most other cancers, do not require surgery.

Types of Non-Hodgkin’s Lymphoma

Non-Hodgkin’s lymphoma is an overall term for a type of cancer that takes many different forms, and which can require different types of care and treatment.

There are so many different types of lymphoma that it’s really a large family of diseases with many different characteristics. “In fact, the disease is so individualized that it’s almost impossible to draw generalizations from one case to another,” Dr. Stefanovic says.

This is why patients who are newly diagnosed with non-Hodgkin’s lymphoma must seek out a specialist with extensive experience in treating the disease. “Lymphomas are of such different types, and there are so many differences being discovered between all the different subtypes and their response to treatment, that it is difficult for anyone who is not a lymphoma expert to keep up,” she notes.

There are three major groups of lymphoma and they are classified by the type of immune cell in which the disease began:

B-CELL LYMPHOMA

This is the most common type of non-Hodgkin’s lymphoma and accounts for about 85 percent of the cases.

T-CELL LYMPHOMA

This type of lymphoma occurs in less than 15 percent of cases.

NK-CELL LYMPHOMA

This is rare form of non-Hodgkin’s lymphoma that accounts for about one percent of cases. NK, which stands for “natural killer” cell, has caused much controversy regarding its classification. The jury is still out as to whether this is a T-cell lymphoma with abnormal markers, or if these destructive cells do, in fact, belong in a class of their own.

NON-HODGKIN’S LYMPHOMA SUBGROUPS

There are also many different subgroups of non-Hodgkin’s lymphoma. Many are rare, but here are the two most common:

Diffuse Large B-Cell Lymphoma (DLBCL)

This type accounts for about 30 percent of cases. It is an aggressive form of non-Hodgkin’s lymphoma that spreads to other organs about 40 percent of the time.

Other (aggressive) types of non-Hodgkin’s lymphoma, which are rarer, include the following:

• Peripheral T-cell lymphoma

• Burkitt’s lymphoma

• Anaplastic large cell lymphoma

• Lymphoblastic lymphoma

Follicular Lymphoma

This slow-growing (indolent) form of non-Hodgkin’s lymphoma accounts for 20 percent of the cases. Although not curable, this form of non-Hodgkin’s lymphoma grows so slowly that 50 percent of those with it live at least 12 more years, and many longer. For some patients, “watchful waiting,” or monitoring, is the sole treatment. In other cases, treatment with a combination of chemotherapy, targeted therapies, monoclonal antibodies (a type of targeted therapy), and/or radiation is required. Sometimes, these slow-growing lymphomas can change into more aggressive types. When that happens, they require aggressive treatment.

Other subtypes of indolent lymphoma include Small lymphocytic lymphoma, which is the same as chronic lymphocytic leukemia (CLL), marginal zone lymphoma/MALT lymphoma, and mantle cell lymphoma. For more on CLL, see the chapter on leukemia.

ADDITIONAL RARE TYPES OF NON-HODGKIN’S LYMPHOMA

• MALT lymphoma: Muscosa associated lymphoid tissue is a B-cell lymphoma that starts in the lining of other organs. MALT lymphoma is most common in the stomach. It is linked to bacterial infection with Helicobacter pylori and can be treated with antibiotics.
• Mantle cell lymphoma: This type of NHL is a B-cell lymphoma, which occurs most often in men over the age of 50. Although classified as low-grade, mantle cell often behaves aggressively and so is treated as such.

Stages of Non-Hodgkin’s Lymphoma

The traditional staging system used for most cancers is not used for non-Hodgkin’s lymphoma. Instead, the main types of non-Hodgkin’s lymphoma are grouped from low-grade (indolent) to high-grade (aggressive). They are characterized according to how quickly they spread as well as the tumor cell’s shape and size. In addition, these classifications are divided into two subtypes, and labeled A and B based on the person’s symptoms. “A” means the person has not experienced the following, “B” symptoms:

• Unexplained weight loss of 10 percent within six months before diagnosis
• Unexplained fever
• Drenching sweats during the night (most commonly) or daytime

Signs and Symptoms

• A painless lump in the neck, armpit, or groin
• An enlarged liver or spleen
• Shortness of breath
• Fever
• Sweating and chills
• Fatigue

Specific Diagnostic Tests

PHYSICAL EXAMINATION

The doctor performs a physical examination, paying special attention to the lymph nodes, liver, and spleen.

BIOPSY

A small amount of tissue is removed, usually from the lymph nodes in the neck, under an arm, or in the groin, and examined under a microscope. In some cases, a biopsy may be taken from the chest or abdomen during a computed tomography (CT scan) or by using an endoscope (a thin, lighted, flexible tube) to take a sample from the stomach or intestine.

IMAGING TESTS

A variety of imaging tests, including CT, MRI, and PET scans, can be used to detect any spread of the cancer.

BONE MARROW BIOPSY AND ASPIRATION

Lymphoma often spreads to the bone marrow. This test is important for both obtaining diagnostic information and staging the disease.

MOLECULAR TESTING

Once a diagnosis of non-Hodgkin’s lymphoma is confirmed, specific tests are performed on the lymphoma cells to identify specific genes, proteins, chromosome changes, and other factors unique to the disease to determine the most effective treatment.

Treatments

The treatment for non-Hodgkin’s lymphoma depends on whether the type is indolent (slow growing), aggressive (fast growing), and where exactly it falls along this scale.

Also, unlike most cancers, which are solid tumors, non-Hodgkin’s lymphoma is a blood cancer, so instead of surgery, the general treatment is usually a combination of chemotherapy and immunological treatments involving monoclonal antibodies (a type of biological treatment). If the disease is severe and aggressive, a bone marrow transplant may be recommended to enable the patient to withstand high doses of chemotherapy.

The following is a description of treatments according to non-Hodgkin’s lymphoma type:

• Diffuse large B-cell lymphoma (DLBCL): In forms of aggressive non-Hodgkin’s lymphoma, the basis for curing or bringing about remission is the administration of chemotherapy drugs, most notably a combination of four drugs that go by the acronym of CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone. Rituxan (rituximab), which is a targeted biological agent that kills cancer cells, is also often used, and radiation can be added if the lymphoma is in a small, localized area. Different chemotherapy regimens can be used if the cancer returns.

• Follicular lymphoma: This is a slow-growing lymphoma that is very treatable but difficult to cure. Treatment depends on several factors. Sometimes, no treatment is recommended until or if symptoms appear. Then, treatment depends on the stage. Treatments can range from radiation, the administration of Rituxan alone or combined with chemotherapy, or the four-drug CHOP regimen. Radioactive monoclonal antibodies are also treatment options, either used alone or in combination with chemotherapy.

STEM CELL TRANSPLANT

A stem cell transplant is sometimes used to treat non-Hodgkin’s lymphoma as a means of curing the disease, or if it returns after remission. This is an intensive procedure that allows doctors to administer higher doses of chemotherapy than would otherwise be tolerated. See chapter 3 for more information.

BONE MARROW TRANSPLANT

Like a stem cell transplant, a bone marrow transplant (from a related or unrelated donor) also enables the administration of high-dose chemotherapy. This treatment is generally reserved for younger patients who are in otherwise good health, and for whom conventional treatments would not result in a cure.