Treatment of Non-Hodgkin Lymphoma in Children, by Type and Stage

In general, children and teens with non-Hodgkin lymphoma (NHL) are treated with chemotherapy (chemo), sometimes along with other drugs. But the exact treatment differs depending on the type and stage of the lymphoma. The treatment for NHL is intense and might cause serious side effects, so it's very important that it is given in a children’s cancer center, especially when it is first started.

Lymphomas in children and teens (especially Burkitt lymphomas) tend to grow very quickly and might already be quite large by the time they’re diagnosed, so it's important to start treatment as soon as possible.

Childhood lymphomas usually respond well to chemo, which can kill large numbers of lymphoma cells in a short period of time. Sometimes this can cause tumor lysis syndrome, a side effect in which chemicals from inside 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 and teens with early-stage (stage I or II) lymphomas are assumed to have more widespread disease than can be detected with exams or 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 childhood NHLs.

Treatment of lymphoblastic lymphoma (LBL)

Stages I and II: In general, treatment for early-stage LBL is similar to the treatment of acute lymphoblastic leukemia (ALL). Chemotherapy is given in 3 phases (induction, consolidation, and maintenance) using many chemo drugs. For example, the BFM regimen uses combinations of many different drugs for the first several months, followed by less intense treatment with methotrexate and 6-mercaptopurine in pill form for a total of about 2 years. Shorter and less intensive treatments, such as the chemo combinations called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and COMP (cyclophosphamide, vincristine, methotrexate, and prednisone), have also been used.

Chemotherapy, usually with methotrexate and possibly 1 or 2 other drugs is also given into the spinal fluid (known as intrathecal chemo) for at least 4 doses, each separated by a week. This 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 LBL is similar to that for earlier stage LBL, although it might be more intensive. It is given as 3 phases of chemo (induction, consolidation, and maintenance) using many drugs, and it lasts for about 2 years. This is very similar to the treatment of high-risk acute lymphoblastic leukemia (ALL).

Intrathecal chemo 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 lymphoma/Burkitt-like lymphoma and diffuse large B-cell lymphoma (DLBCL)

Chemotherapy (chemo), often along with the monoclonal antibody rituximab, is the main form of treatment for these lymphomas. This combination is sometimes called chemoimmunotherapy.

Stages I and II: While chemo (often along with rituximab) is the main treatment of these lymphomas, surgery may be done before chemo if the tumor is in only one area, such as a large abdominal (belly) tumor.

Several different chemo drugs are used. The length of treatment ranges from about 9 weeks to 6 months. Most pediatric oncologists feel that the 9-week treatment is adequate if all of the tumor is removed with surgery first.

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 lymphomas are generally treated with rituximab plus more intensive chemotherapy. Because these lymphomas tend to grow quickly, the chemo cycles are short, with little rest between courses of treatment.

For example, a treatment plan known as the French LMB protocol regimen alternates between different combinations of drugs every 3 to 4 weeks for a total of about 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 anaplastic large cell lymphoma (ALCL)

Chemotherapy (chemo) is the main form of treatment for childhood ALCL. Studies are being done to determine if adding another drug to chemo, such as crizotinib (Xalkori) or brentuximab vedotin (Adcetris), might make treatment more effective.

Stages I and II: Treatment for these lymphomas usually consists of chemo with 4 or more drugs given for about 3 to 6 months. The usual chemo regimen contains a 4-drug combination of cyclophosphamide, vincristine, prednisone, and either doxorubicin or methotrexate. (These are known as the CHOP or COMP regimens.)

Chemo is given into the spinal fluid only if the lymphoma is near the head or neck.

Stages III and IV: ALCL doesn’t often reach the bone marrow or spinal fluid, but if it does, it requires more intensive treatment. Chemo typically includes several drugs given over 9 to 12 months.

Intrathecal chemotherapy is given into the spinal fluid as well.

Treatment of recurrent lymphoma

Generally, if the lymphoma comes back (recurs) after the first treatment, it is harder to treat. When possible, more intensive chemotherapy, usually including a stem cell transplant, is recommended. This is often done as part of a clinical trial.

For some types of childhood lymphoma, other types of treatment might be an option. For example, if ALCL is no longer responding or comes back after treatment, non-chemo drugs such as brentuximab vedotin or an ALK inhibitor (such as crizotinib) might be an option, if they haven’t been tried already.

Clinical trials of other new forms of treatment may also be an option for recurrent childhood NHL.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Bollard CM, Lim MS, Gross TG; COG Non-Hodgkin Lymphoma Committee. Children’s Oncology Group’s 2013 blueprint for research: Non-Hodgkin lymphoma. Pediatr Blood Cancer. 2013;60:979–984.

Gross TG, Kamdar KY, Bollard CM. Chapter 19: Malignant Non-Hodgkin Lymphomas in Children. In: Blaney SM, Adamson PC, Helman LJ, eds. Pizzo and Poplack’s Principles and Practice of Pediatric Oncology. 8th ed. Philadelphia Pa: Lippincott Williams & Wilkins; 2021.

Minard-Colin V, Aupérin A, Pillon M, et al. Rituximab for high-risk, mature B-cell non-Hodgkin's lymphoma in children. N Engl J Med. 2020;382(23):2207-2219.

Mosse YP, Lim MS, Voss SD, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: A Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013;14:472−480.

National Cancer Institute Physician Data Query (PDQ). Childhood Non-Hodgkin Lymphoma Treatment. 2021. Accessed at https://www.cancer.gov/types/lymphoma/hp/child-nhl-treatment-pdq on June 14, 2021.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Pediatric Aggressive Mature B-Cell Lymphomas. Version 2.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/ped_b-cell.pdf on July 1, 2021.

Sandlund JT, Onciu M. Chapter 94: Childhood Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Termuhlen AM, Gross TG. Overview of non-Hodgkin lymphoma in children and adolescents. UpToDate. 2021. Accessed at https://www.uptodate.com/contents/overview-of-non-hodgkin-lymphoma-in-children-and-adolescents on June 14, 2021.

References

Bollard CM, Lim MS, Gross TG; COG Non-Hodgkin Lymphoma Committee. Children’s Oncology Group’s 2013 blueprint for research: Non-Hodgkin lymphoma. Pediatr Blood Cancer. 2013;60:979–984.

Gross TG, Kamdar KY, Bollard CM. Chapter 19: Malignant Non-Hodgkin Lymphomas in Children. In: Blaney SM, Adamson PC, Helman LJ, eds. Pizzo and Poplack’s Principles and Practice of Pediatric Oncology. 8th ed. Philadelphia Pa: Lippincott Williams & Wilkins; 2021.

Minard-Colin V, Aupérin A, Pillon M, et al. Rituximab for high-risk, mature B-cell non-Hodgkin's lymphoma in children. N Engl J Med. 2020;382(23):2207-2219.

Mosse YP, Lim MS, Voss SD, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: A Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013;14:472−480.

National Cancer Institute Physician Data Query (PDQ). Childhood Non-Hodgkin Lymphoma Treatment. 2021. Accessed at https://www.cancer.gov/types/lymphoma/hp/child-nhl-treatment-pdq on June 14, 2021.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Pediatric Aggressive Mature B-Cell Lymphomas. Version 2.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/ped_b-cell.pdf on July 1, 2021.

Sandlund JT, Onciu M. Chapter 94: Childhood Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Termuhlen AM, Gross TG. Overview of non-Hodgkin lymphoma in children and adolescents. UpToDate. 2021. Accessed at https://www.uptodate.com/contents/overview-of-non-hodgkin-lymphoma-in-children-and-adolescents on June 14, 2021.

Last Revised: August 10, 2021

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