The Many Faces of Lymphoma

The most common form of blood cancer is much more than just one disease.

In 2006, pitcher Jon Lester of the Boston Red Sox was undergoing chemotherapy for anaplastic large cell lymphoma, a potentially fatal cancer of the immune system, yet seven years later he won two 2013 W­­orld Series games.

Like Lester, many of the more than 70,000 people diagnosed with lymphoma each year survive because of advancements in chemotherapy and other treatments. However, most people don’t realize that this cancer is actually a  large group of distinct diseases. Which therapies they receive and how well they will respond to treatment depend on the type of lymphoma they develop.

Lymphoma, the most common form of blood cancer, occurs when the immune system produces too many of the cells called lymphocytes, which normally guard the body against viruses and bacteria. These cells multiply normally in the course of an infection, leading to swollen lymph nodes, such as in mumps or mono, but after the infection has subsided, the cells die off and the lymph nodes return to normal size. When these lymphocytes become malignant, they multiply continuously and lymph nodes become larger and larger even in the absence of an infection.  Hodgkin’s lymphoma, one of the many subtypes of lymphoma, is a remarkable treatment success story. The vast majority of patients are cured with chemotherapy and or radiation therapy.  Patients have a more than 80 percent chance of cure even when the cancer has widely spread throughout the body.

Hodgkin’s lymphoma is characterized by the presence of an abnormal cell called the Reed-Sternberg. All other lymphomas—those that do not have Reed-Sternberg cells—are lumped into a category called non-Hodgkin lymphoma (NHL).

There are more than 30 different types of NHL. Some forms are treated differently than others. For example, anaplastic large cell lymphoma, the type of lymphoma that Jon Lester was diagnosed with, often responds well to a chemotherapy regimen called CHOP, which includes four drugs:  cyclophosphamide, doxorubicin, vincristine and prednisone. CHOP also works against other NHL sub-types that fall within the same category as anaplastic large cell lymphoma, known as peripheral T cell lymphomas.

The most common type of NHL, diffuse large B cell lymphoma (DLBCL), is also treatable and potentially curable. This fast-growing lymphoma  accounts for about one third of NHL cases. For this lymphoma, it is typical for lymph nodes to double in size every month, and patients often present within a few months of having noted an enlarged lymph node. The typical first line treatment is a modified version of CHOP, known as R-CHOP, that adds a “targeted therapy” called rituximab which is  a monoclonal antibody, that homes directly to the cancer cells and promotes their destruction.  Over 90 percent of patients with localized, early stage DLBCL will be cured with a combination of R-CHOP and radiation therapy and approximately 50 percent of patients with advanced stage DLBCL will be cured with R-CHOP. Unfortunately for those patients who are not cured by R-CHOP there are less attractive second line therapies, including chemotherapy or high dose chemotherapy followed by autologous stem cell rescue, also known as bone marrow transplant. Many fewer can be cured at that point and the majority of these patients will not survive their disease.

The second most common subtype of NHL, follicular lymphoma (FL), grows slowly, with lymph nodes doubling in size approximately every six to 12 months, and patients often get diagnosed a year or later after they first noted an enlarged lymph node. Many patients may not require treatment initially and can just be observed. A small fraction never require treatment, however, eventually, the vast majority of  patients will require therapy which is typically rituximab combined with a chemotherapy. Unlike DLBCL, patients with FL are rarely if ever cured but may live many years  because of the slow growth of the tumor cells and the ability to treat with multiple therapies. Eventually, however, most patients will die of their disease and in about 25 percent of them their FL will transform to DLBCL which is typically not responsive to therapy in this setting.

Another type of NHL that responds to chemotherapy is Burkitt’s lymphoma. Doctors first noticed this cancer in children in Africa, but it also strikes people infected with human immunodeficiency virus (HIV), organ transplant recipients, and others. Chemotherapy combinations cure about 50 percent of patients, meaning there are many who need other choices. This lymphoma is very rapidly growing, and lymph nodes double in size within a few days to a few weeks. While it is rapidly growing, it is curable in many patients when diagnosed early.

Mantle cell lymphoma (MCL) only accounts for about five percent of the cases of NHL but it is a very aggressive type of lymphoma  and is typically diagnosed in very advanced stages of the disease. Treatments like R-CHOP have improved the prognosis for patients, who now survive for five to seven years on average, but the disease recurs in nearly all patients and cures are extremely rare.  Continued scientific advancements  are providing  additional options for patients

The picture however is continuing to improve for all of the lymphomas with the continued research and development of exciting therapies that specifically target the cancer cells, and agents that modify the immune system. These new therapies include monoclonal antibodies that target directly to the cancer cells and kill the cancer cells by a variety of immune mechanisms, monoclonal antibodies that are “packaged” with toxic chemicals that target directly to the cancer cells to deliver these toxic agents, and tyrosine kinase inhibitors that are small molecules that can be given orally and target different growth receptors in cancer cells and very effectively kill the cancer cells, and other agents to stimulate the immune system. This is perhaps the most exciting era in lymphoma history where basic science discoveries are becoming available to lymphoma patients with the hope of  improving their survival and  quality of life.