Non-Hodgkin lymphoma arises when the genetic material of a lymphocyte is damaged and becomes malignant, or cancerous — able to grow and spread uncontrollably. Lymphocytes include B cells, T cells, and NK cells, different types of white blood cells that perform important functions in the immune system. The malignant cell begins producing identical copies of itself, or clones. Over time, these malignant cells can spread to neighboring groups of lymph nodes or tissues and, if not treated, can spread to other parts of the body.
The majority of non-Hodgkin lymphomas develop from B cells. These lymphocytes progress through a number of different stages. Lymphoma can develop at each stage, and each stage is associated with a particular malignancy with its own specific behavior.
Types of Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma is actually a complex group of about 50 different cancers. Although many forms of non-Hodgkin lymphoma exist, the 13 most common types account for 88 percent of all cases in the United States. Memorial Sloan-Kettering also has special expertise treating approximately 25 other very rare forms of non-Hodgkin lymphoma, owing to highly trained staff, a large patient base, and a high number of referrals for these rare cancers.
If tests indicate that you have non-Hodgkin lymphoma, our physicians are experts at determining what type of lymphoma it is. We will also stage the disease to learn if and where it has spread from its site of origin. This information is crucial in selecting the most-effective treatment.
Physicians also divide all types of non-Hodgkin lymphoma into two groups: indolent (or low grade) lymphomas, which grow more slowly and have fewer symptoms, and aggressive lymphomas, which grow more quickly. Patients with indolent lymphomas may live without symptoms for several years or even decades, but the indolent non-Hodgkin lymphomas are more difficult to cure than the aggressive forms of the disease. Aggressive lymphomas are generally more curable, but can quickly lead to death if not treated.
Your doctors at Memorial Sloan-Kettering will develop a treatment strategy based on whether your lymphoma is aggressive or indolent, and whether it is at an early or advanced stage. Below are some of the standard approaches to treatment of various forms of non-Hodgkin lymphoma.
Treatment for Indolent Non-Hodgkin Lymphoma
The following are treatment options for different stages of indolent non-Hodgkin lymphoma:
Early-Stage Disease (Stage I and Contiguous Stage II)
Lymphoma is considered early stage when the disease is localized — that is, has not spread from its site of origin — or has spread only to nearby lymph nodes. Patients with early-stage disease can be treated with radiation to specific lymph nodes where lymphoma has been detected, or to “extended fields,” which include nearby lymph nodes. Radiation may or may not be combined with chemotherapy. Sometimes no therapy is required.
Advanced-Stage Disease (Non-Contiguous Stage II/III/IV)
Treatment for indolent, advanced-stage disease depends on the specific situation. Many times active surveillance without therapy is the best approach.
Active surveillance is not the same thing as receiving no treatment. It is a dynamic disease-management option in which your doctor regularly monitors your cancer for any signs of progression, and reevaluates your treatment if the cancer becomes more active. Our doctors recommend active surveillance when you are not experiencing any symptoms of lymphoma and treatment is unlikely to cure the disease but would cause unpleasant side effects. Many patients are on active surveillance for several years without therapy. Sometimes the lymphoma gets better on its own. Some patients are never treated at all.
Active surveillance is not a good option, however, for patients whose tumor burden is high. Patients with a high tumor burden typically have large tumors or many smaller ones, blood count problems, or symptoms such as pain or fever. Sometimes organs like the kidney, lung, or liver are affected.
For these patients, treatment could involve chemotherapy. Patients with high tumor burden are also potential candidates for treatment with biology-based therapies such as monoclonal antibodies, interferon, or vaccines.
Recurrent Indolent Disease
Indolent lymphomas tend to come back after the initial treatment in most patients. This can take years, but sometimes happens soon after the first therapy. Standard drugs for non-Hodgkin lymphoma do not cure patients whose disease has relapsed. Indolent non-Hodgkin lymphoma can recur in exactly the same form, or it can return in an aggressive form if it has undergone a process called histologic transformation.
Memorial Sloan-Kettering offers a variety of treatment options for patients whose lymphoma has relapsed. Your doctor will help you to choose the best treatment for you. Treatments may include:
- Systemic therapies including immune therapy, chemotherapy, radioactive antibodies that attach to and destroy diseased cells in the body, and a variety of new therapies that are currently under investigation in our clinical trials.
- High-dose therapy and stem cell transplantation. In some cases, a patient's own stem cells are harvested and then returned to him or her after intensive chemotherapy, producing healthy new blood cells. This is called an autologous transplantation. A small number of patients receive a transplantation of stem cells from another person, called an allogeneic transplantation. High-dose therapy plus stem cell transplantation can often cure the lymphoma, but has many side effects. Learn more about stem cell transplantation.
Treatment for Aggressive Non-Hodgkin Lymphoma
The following are treatment options for different stages of aggressive non-Hodgkin lymphoma:
Early-Stage and Advanced-Stage Disease (Stage I, Contiguous Stage II & Non-Contiguous Stage II/III/IV)
Patients with early-stage aggressive non-Hodgkin lymphoma often receive chemotherapy combined with radiation therapy. The most commonly used chemotherapy program is R-CHOP: rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin or Adriamycin), vincristine (Oncovin-), and prednisone. Rituximab is a monoclonal antibody, or specialized protein, that binds to B cells, including most lymphoma B cells. It helps the immune system destroy the cancer cells and makes the chemotherapy more powerful.
Patients with advanced, aggressive non-Hodgkin lymphoma receive chemotherapy. The most common chemotherapy is R-CHOP. Doctors at Memorial Sloan-Kettering have also pioneered a treatment for higher-risk patients that uses R-CHOP followed by ICE. ICE is a combination of three chemotherapeutic agents (ifosfamide, carboplatin, etoposide) that is typically used for recurrent aggressive lymphoma, but may improve the outcome in some patients if used after R-CHOP.1
Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma, accounting for up to 30 percent of newly diagnosed cases. DLBCL is a fast-growing lymphoma. It can arise in lymph nodes or outside of the lymphatic system, in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain.
About 60 percent of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with the chemotherapy regimen called R-CHOP-21. However, some patients cannot be cured with this regimen.2
Memorial Sloan-Kettering physicians developed an approach called “risk-adapted therapy” that is given to patients with certain risk factors that indicate they have a higher risk of not being cured by R-CHOP-21 alone. This regimen includes a combination of chemotherapy drugs called ICE, periodic PET scans, and for some patients, a stem cell transplant.
By including risk adapted therapy as a treatment option, a recent study showed 80 percent progression-free survival for patients with this kind of lymphoma who were treated at Memorial Sloan-Kettering.1
Recurrent Aggressive Disease
For patients whose disease has relapsed, high-dose chemotherapy followed by bone marrow or peripheral blood stem cell transplantation is more effective than chemotherapy alone. Transplantation is now often preceded by the ICE combination treatment described above, or similar treatments.
After the completion of your treatment, you will see your physicians for frequent follow-up exams. They will watch for any side effects of treatment and for signs of the recurrence of disease. During these check-ups, you may undergo tests including a physical exam, blood tests, bone marrow aspirates, biopsies, and x-rays or other imaging. If you experience any new symptoms, you should contact your physicians, even between visits. The sooner these symptoms are evaluated and treated, the better the outcome is likely to be.
The length of follow-up care and the frequency of visits depend on the nature of your disease, its stage, and the treatments you received. After a few years of follow-up, some patients can be followed by their internists and see their oncologist on an as-needed basis.
Moskowitz CH, Schöder H, Teruya-Feldstein J, Sima C, Jasonos A, Portlock CS, Straus D, Noy A, Palomba MK, O'Connor OA, Horwitz S, Weaver SA, Meikle JL, Filippa DA, Caravelli JF, Hamlin PA, Zelenetz AD. Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in advanced-stage diffuse large B-cell lymphoma. J Clin Oncol. 2010 Apr 10;28(11):1896-903. [PubMed Abstract]
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. [PubMed Abstract]