In 1832 a distinguished English physician named Thomas Hodgkin reported on a group of patients who had a rapidly fatal disease characterized by greatly enlarged lymph nodes and swelling of the liver and spleen. He did not know what caused the disease and did not mention cancer in his seminal publication. He treated one patient with “cascarilla and soda” without effect and recommended “caustic potash” for less advanced cases. Please don’t ask me what these treatments were! Let’s just be relieved and grateful to the physicians and scientists who have contributed to today’s understanding that Hodgkin’s disease is a type of lymphoma (now called Hodgkin lymphoma) and that modern treatments can cure more than 75 percent of cases.
Lymphomas are the most common hematologic malignancy. There are two main categories, Hodgkin lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). NHL occurs much more often than HL. The type is determined by a pathologist’s analysis of a biopsy specimen. Lymphomas can arise virtually anywhere in the body because of the widespread distribution of lymph cells and lymph nodes. Although lymphomas may cause any of a number of symptoms, most cases are detected after a patient feels a swollen lymph node or the enlarged node presses on a vital organ, causing internal symptoms.
If the diagnosis is non-Hodgkin’s lymphoma, testing will reveal if it derives from B- or T-cells (80 percent are from B-cells). Hodgkin lymphoma is always of B-cell origin. Current classification systems recognize five types of HL and more than thirty types of NHL. Whereas HL mainly affects young adults and those fifty-five or older, NHL typically affects those over age fifty (some forms are more common in younger individuals). In appendix 2, I list many excellent resources to learn about both HL and NHL. For the remainder of this section, I focus on non-Hodgkin’s lymphoma.
Decades of sophisticated scientific research into the mysteries of the immune system have enabled us to understand the origins of the many kinds of non-Hodgkin’s lymphoma. Normal lymphocytes go through a multistep process of maturation from bone marrow stem cell to fully functional infection-fighting immune cell. Each step is represented by a specific cell type, and each of these cells can be affected by the malignant process and give rise to a lymphoma. This is why there are so many types of NHL.
The oncologist will tell a patient the specific type of NHL he or she has. Follicular lymphoma and diffuse large cell lymphoma are the two most common types; less common types include small lymphocytic, mantle cell, lymphoplasmacytic (Waldenstrom’s macroglobulinema), MALT (mucosa-associated lymphatic tissue), and peripheral T-cell lymphomas. The doctor will also state whether it falls into the low-, intermediate-, or high-grade category. The grade relates to how aggressively the lymphoma is likely to grow: low-grade types grow over years, whereas intermediate-grade lymphomas grow over months, and high-grade lymphomas grow even faster. To relate this to the concepts of growth and apoptosis described in chapter 1, low-grade lymphomas are marked by diminished apoptosis, whereas intermediate- and high-grade lymphomas have accelerated growth as their defining characteristic.
If lymphoma can be thought of as a pot of boiling water, then low-grade lymphomas are at a gentle simmer, whereas high-grade ones are on a rapid boil. The faster growing the lymphoma, the more urgent the need for treatment. It is also often the case that the faster growing the lymphoma, the
greater the chances that it can be eradicated with chemotherapy. This is why patients with diffuse large cell lymphoma, for example, are told that there is a good chance for cure with treatment, whereas those with low-grade lymphomas are told that we do not yet know how to eradicate this disease.
As illustrated by the case of Don, the seventy-five-year-old with lymphoma described in chapter 1, some low-grade lymphomas are observed closely and not treated until necessary; approximately 20 percent will actually undergo spontaneous remission and shrink for a time without treatment. If fever, night sweats, weakness, or progressive enlargement of lymph nodes occurs, then treatment might be necessary. When the time comes, a number of highly effective treatments are available to control the disease.
Just as I have emphasized in other cancers, no two lymphomas are exactly alike. Focusing on the most common type of NHL, B-cell diffuse large cell lymphoma, about half of all cases will be cured with a treatment regimen called CHOP-Rituxan. This consists of three chemotherapy drugs administered intravenously (C = Cytoxan or cyclophosphamide, H = hydroxy-daunorubicin or doxorubicin/Adriamycin, and O = Oncovin or vincristine); an oral steroid medicine, called prednisone (P); and a genetically engineered antibody that specifically attacks B-cell lymphomas, called rituximab (Rituxan), which is administered intravenously along with chemotherapy.
Can it be predicted who will and who won’t be cured with CHOPRituxan?
Oncologists employ a prognostic system called the IPI (International Prognostic Index) to each case of diffuse large cell lymphoma to classify it into a low-, intermediate-, or high-risk category; the higher the risk, the lower the chances for cure. A related system called the FLIPI (Follicular Lymphoma IPI) can be applied to cases of follicular lymphoma. Both the IPI and the FLIPI use clinical information, such as the patient’s age, the stage of the cancer, and the elevation (or lack thereof ) of the blood marker LDH (lactate dehydrogenase). But it is not a perfect way to predict survival. A more sophisticated method based on determining the genetic makeup of the lymphoma is being pioneered and is hoped to be available in the near future.
Patients with NHL often confront a complex disease that has many good treatment options. New and effective therapies for lymphoma are rapidly being developed. Cure or long-term disease control should always be the goal. This may be achieved with chemotherapy drugs, antibody therapies, radioactive antibodies, or a stem cell transplant. Although innovative approaches such as lymphoma-specific vaccines were not successful in recently performed clinical trials, harnessing a patient’s own immune system to control his or her lymphoma will continue to be a major focus of researchers.
