Treatment of non-Hodgkin lymphoma by type and stage

In general, all children with non-Hodgkin lymphoma are treated with chemotherapy, but the treatments differ depending on the type and stage of the lymphoma.

Lymphomas in children (especially Burkitt lymphomas) tend to grow very quickly and may be quite large when diagnosed, so it is important to start treatment as soon as possible. These lymphomas usually respond well to chemotherapy, which can kill large numbers of lymphoma cells in a short period of time. This can cause tumor lysis syndrome, a side effect in which the inner contents of the dead cells enter the blood and can cause problems with the kidneys and other organs. Doctors try to prevent this by making sure the child gets lots of fluids before and during treatment, and by giving certain drugs to help the body get rid of these substances.

Even children with early stage (stage I or II) lymphomas are assumed to have more widespread disease than might be visible with imaging tests. Because of this, local treatments such as surgery or radiation therapy alone are very unlikely to cure them. Therefore, chemotherapy is an important part of treatment for all children.

Treatment of lymphoblastic lymphoma

Stages I and II: Treatment is with chemotherapy that combines several drugs. For example, doctors may use combinations such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or COMP (cyclophosphamide, vincristine, methotrexate, and prednisone) for a few months, followed by less intense treatment with methotrexate and 6-mercaptopurine in pill form for several months. Many doctors now feel that combinations containing even more drugs, similar to the treatment of acute lymphoblastic leukemias, might be more successful. For example, a combination called the BFM regimen uses 8 drugs for the first 2 months followed by less intense treatment with methotrexate and 6-mercaptopurine in pill form for a total of about 2 years.

Intrathecal chemotherapy, usually with methotrexate, is also given into the spinal fluid for at least 4 doses, each separated by a week. This chemotherapy helps kill any lymphoma cells in the brain or spinal cord.

The total length of treatment may be as long as 2 years.

Stages III and IV: The treatment for children with advanced lymphoblastic lymphoma lasts for about 2 years. Treatment is typically more intensive than for earlier stage lymphomas. It is given as 3 phases of chemotherapy (induction, consolidation, and maintenance) using many drugs. This is very similar to the treatment of high-risk acute lymphoblastic leukemia (ALL). For more information, see the treatment section of the document, Childhood Leukemia.

Intrathecal chemotherapy is also given into the spinal fluid to kill any lymphoma cells that may have reached the brain or spinal cord. In some cases, radiation therapy may be given to the brain and spinal cord as well.

Treatment of Burkitt and Burkitt-like lymphoma

Chemotherapy is the main form of treatment for these lymphomas. Studies are now being done to determine whether adding a monoclonal antibody such as rituximab to chemotherapy will make treatment more effective.

Stages I and II: Treatment of these lymphomas may include surgery prior to chemotherapy if the tumor is in only one area. If there is a large abdominal tumor, it is important that as much as possible be removed. After that, chemotherapy is given.

The length of treatment ranges from about 9 weeks to 6 months, depending on whether all of the tumor were removed with surgery. Several drugs are used, most commonly prednisone, vincristine, cyclophosphamide, ara-C, doxorubicin, and methotrexate. Most pediatric oncologists feel that the 9-week treatment is adequate if all of the tumor has been removed. Chemotherapy into the spinal fluid is needed only if the lymphoma is growing around the head or neck.

Stages III and IV: Children with more advanced Burkitt lymphoma need more intensive chemotherapy. Because these lymphomas tend to grow quickly, the chemotherapy cycles are short, with little rest between courses of treatment.

For example, a treatment plan known as the French LMB protocol regimen alternates prednisone, cyclophosphamide, doxorubicin, and vincristine with cytarabine (ara-C) and methotrexate every 3 to 4 weeks for a total of 6 to 8 months. Other similar treatment regimens are the German BFM protocol and the St. Jude Total B regimen. Chemotherapy must also be given into the spinal fluid.

Treatment of large cell (including anaplastic) lymphoma

Chemotherapy is the main form of treatment for these lymphomas. Studies are being done to determine whether adding rituximab or other monoclonal antibodies to chemotherapy might make treatment more effective.

Stages I and II: Treatment for these lymphomas usually consists of chemotherapy with 4 or more drugs given for around 3 to 6 months. For diffuse large B-cell lymphoma, treatment may include surgery in addition to chemotherapy. The usual chemotherapy regimen contains a 4-drug combination of cyclophosphamide, vincristine, prednisone, and either doxorubicin or methotrexate. (These are known as the CHOP or COMP regimens.) Chemotherapy is given into the spinal fluid only if the lymphoma is near the head or neck.

Stages III and IV: Large cell lymphomas don’t often reach the bone marrow or spinal fluid, but if they do they require more intensive treatment.

Chemotherapy is usually doxorubicin, prednisone, vincristine, methotrexate, and possibly 6-mercaptopurine or cyclophosphamide over 9 to 12 months. Some doctors treat advanced large B-cell lymphomas as they would Burkitt lymphoma (see above). Intrathecal chemotherapy is given into the spinal fluid as well.

Current clinical trials are focusing on the length of treatment, which drugs are important in treating large cell lymphoma, and whether the different types of large cell lymphoma can be treated similarly.

Treatment of recurrent lymphoma

Generally, if the lymphoma comes back after the first therapy, it is much harder to treat. When possible, more intensive chemotherapy, usually including a stem cell transplant, is recommended. This is often done in the context of a clinical trial. Clinical trials of newer forms of treatment may also be an option.