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Overview of non-Hodgkin lymphoma in children and adolescents

Amanda M Termuhlen, MD
Thomas G Gross, MD, PhD
Section Editor
Julie R Park, MD
Deputy Editor
Alan G Rosmarin, MD


Non-Hodgkin lymphoma (NHL) consists of a diverse group of malignant neoplasms of the lymphoid tissues variously derived from B cell progenitors, T cell progenitors, mature B cells, or mature T cells. Unlike in adults where low-grade, clinically indolent NHL subtypes predominate, most pediatric NHL cases are of high grade and have an aggressive clinical behavior [1]. Whenever possible, children with NHL should be treated in a comprehensive pediatric oncology center by a multidisciplinary team experienced in the diagnosis and care of children with cancer.

This topic will provide an overview of NHL in children and adolescents, focusing on issues that are of interest to primary care providers. The pathobiology of NHL and its diagnosis and management in adults are presented separately, as is an overview of Hodgkin lymphoma in children and adolescents. (See "Classification of the hematopoietic neoplasms" and "Clinical presentation and diagnosis of non-Hodgkin lymphoma" and "Overview of Hodgkin lymphoma in children and adolescents".)


NHL is the fifth most common diagnosis of pediatric cancer in children under the age of 15 years, and it accounts for approximately 7 percent of childhood cancers in the developed world [2]. In the United States, approximately 800 new cases of pediatric NHL are diagnosed annually with an incidence of 10 to 20 cases per million people per year [3-6]. This incidence appears to be increasing overall, largely thought to reflect a rise in NHL among adolescents. The median age at diagnosis is approximately 10 years, and the incidence increases with age [2]. Lymphomas are rare in infants (≤1 percent) and account for approximately 4, 14, 22, and 25 percent of neoplasms in children age 1 to 4, 5 to 9, 10 to 14, and 15 to 19 years, respectively. There is a male predominance, and whites are more commonly affected than African Americans.

The incidence and distribution of specific NHL subtypes differs by population (eg, age, race) and geographical region. In general, the most common subtypes of pediatric NHL are derived from B cell progenitors. In the United States and other developed countries, the most common subtypes are Burkitt lymphoma, diffuse large B cell lymphoma, lymphoblastic T cell or B cell lymphoma, and anaplastic large cell lymphoma [6]. Other subtypes (eg, follicular lymphoma, marginal zone lymphoma) are less common, accounting for approximately 7 percent of pediatric NHL.

Both congenital and acquired immunodeficiency syndromes are associated with an increased risk of NHL. Congenital immunodeficiencies associated with NHL include common variable immunodeficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia, and X-linked lymphoproliferative syndrome. Congenital immunodeficiencies may impact treatment decisions. As an example, the use of diagnostic tests and therapy involving x-rays and ionizing radiation should be limited in children with ataxia telangiectasia to minimize the risk of somatic mutations and subsequent malignancy. Acquired immunodeficiencies include HIV and the use of immunosuppressive medications. Post-transplant lymphoproliferative disorders can follow solid organ and hematopoietic cell transplantation. (See 'Lymphoproliferative disease in the immune compromised patient' below and "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders" and "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders", section on 'Epidemiology' and "Ataxia-telangiectasia".)

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Literature review current through: Dec 2017. | This topic last updated: Jan 13, 2017.
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  1. Morton LM, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood 2006; 107:265.
  2. Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev 2010; 36:277.
  3. Crump C, Sundquist K, Sieh W, et al. Perinatal and family risk factors for non-Hodgkin lymphoma in early life: a Swedish national cohort study. J Natl Cancer Inst 2012; 104:923.
  4. Steliarova-Foucher E, Stiller C, Kaatsch P, et al. Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCISproject): an epidemiological study. Lancet 2004; 364:2097.
  5. Emmanuel B, Anderson WF. Non-Hodgkin lymphoma in early life. J Natl Cancer Inst 2012; 104:888.
  6. Percy CL, Smith MA, Linet M, et al. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. NIH Pub.No. 99-4649., pp 35-50, National Cancer Institute, SEER Program; National Cancer Institute, Bethesda, MD 1999.
  7. Salzburg J, Burkhardt B, Zimmermann M, et al. Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin-Frankfurt-Munster Group Report. J Clin Oncol 2007; 25:3915.
  8. Cairo MS, Sposto R, Gerrard M, et al. Advanced stage, increased lactate dehydrogenase, and primary site, but not adolescent age (≥ 15 years), are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB LMB 96 study. J Clin Oncol 2012; 30:387.
  9. Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007; 25:571.
  10. Swerdlow SH, Campo E, Harris NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues, IARC Press, Lyon 2008.
  11. Sandlund JT, Downing JR, Crist WM. Non-Hodgkin's lymphoma in childhood. N Engl J Med 1996; 334:1238.
  12. Sills RH. The spleen and lymph nodes. In: Oski's Pediatrics. Principles and Practice, 4th ed, McMillan JA, Feigin RD, DeAngelis C, Jones MD (Eds), Lippincott, Williams & Wilkins, Philadelphia 2006. p.1717.
  13. Heiberg E, Wolverson MK, Sundaram M, Nouri S. Normal thymus: CT characteristics in subjects under age 20. AJR Am J Roentgenol 1982; 138:491.
  14. Murphy SB. The national impact of clinical cooperative group trials for pediatric cancer. Med Pediatr Oncol 1995; 24:279.
  15. Murphy SB. Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults. Semin Oncol 1980; 7:332.
  16. Rosolen A, Perkins SL, Pinkerton CR, et al. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol 2015; 33:2112.
  17. Corrigan JJ, Feig SA, American Academy of Pediatrics. Guidelines for pediatric cancer centers. Pediatrics 2004; 113:1833.
  18. Link MP, Shuster JJ, Donaldson SS, et al. Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med 1997; 337:1259.
  19. Burkhardt B, Woessmann W, Zimmermann M, et al. Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. J Clin Oncol 2006; 24:491.
  20. Sandlund JT, Pui CH, Zhou Y, et al. Effective treatment of advanced-stage childhood lymphoblastic lymphoma without prophylactic cranial irradiation: results of St Jude NHL13 study. Leukemia 2009; 23:1127.
  21. Seidemann K, Tiemann M, Schrappe M, et al. Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 2001; 97:3699.
  22. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
  23. Jairam V, Roberts KB, Yu JB. Historical trends in the use of radiation therapy for pediatric cancers: 1973-2008. Int J Radiat Oncol Biol Phys 2013; 85:e151.
  24. Reiter A, Schrappe M, Ludwig WD, et al. Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood 2000; 95:416.
  25. Termuhlen AM, Smith LM, Perkins SL, et al. Outcome of newly diagnosed children and adolescents with localized lymphoblastic lymphoma treated on Children's Oncology Group trial A5971: a report from the Children's Oncology Group. Pediatr Blood Cancer 2012; 59:1229.
  26. Termuhlen AM, Smith LM, Perkins SL, et al. Disseminated lymphoblastic lymphoma in children and adolescents: results of the COG A5971 trial: a report from the Children's Oncology Group. Br J Haematol 2013; 162:792.
  27. Gross TG, Hale GA, He W, et al. Hematopoietic stem cell transplantation for refractory or recurrent non-Hodgkin lymphoma in children and adolescents. Biol Blood Marrow Transplant 2010; 16:223.
  28. Laver JH, Kraveka JM, Hutchison RE, et al. Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial. J Clin Oncol 2005; 23:541.
  29. Le Deley MC, Rosolen A, Williams DM, et al. Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial. J Clin Oncol 2010; 28:3987.
  30. Pillon M, Gregucci F, Lombardi A, et al. Results of AIEOP LNH-97 protocol for the treatment of anaplastic large cell lymphoma of childhood. Pediatr Blood Cancer 2012; 59:828.
  31. Brugières L, Quartier P, Le Deley MC, et al. Relapses of childhood anaplastic large-cell lymphoma: treatment results in a series of 41 children--a report from the French Society of Pediatric Oncology. Ann Oncol 2000; 11:53.
  32. Brugières L, Pacquement H, Le Deley MC, et al. Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma: a report from the French Society of Pediatric Oncology. J Clin Oncol 2009; 27:5056.
  33. Alexander S, Kraveka JM, Weitzman S, et al. Advanced stage anaplastic large cell lymphoma in children and adolescents: results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: a report from the children's oncology group. Pediatr Blood Cancer 2014; 61:2236.
  34. Woessmann W, Peters C, Lenhard M, et al. Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt-Münster group report. Br J Haematol 2006; 133:176.
  35. Harris RE, Termuhlen AM, Smith LM, et al. Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Children's Oncology Group study A5962. Biol Blood Marrow Transplant 2011; 17:249.
  36. Woessmann W, Zimmermann M, Lenhard M, et al. Relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster (BFM)-type first-line therapy: a BFM-group study. J Clin Oncol 2011; 29:3065.
  37. Okeley NM, Miyamoto JB, Zhang X, et al. Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res 2010; 16:888.
  38. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125388s000,125399s000lbl.pdf (Accessed on August 22, 2011).
  39. Gambacorti-Passerini C, Messa C, Pogliani EM. Crizotinib in anaplastic large-cell lymphoma. N Engl J Med 2011; 364:775.
  40. Foyil KV, Bartlett NL. Brentuximab vedotin and crizotinib in anaplastic large-cell lymphoma. Cancer J 2012; 18:450.
  41. Mossé 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.
  42. Gerrard M, Cairo MS, Weston C, et al. Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Br J Haematol 2008; 141:840.
  43. Patte C, Auperin A, Gerrard M, et al. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood 2007; 109:2773.
  44. Cairo MS, Gerrard M, Sposto R, et al. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood 2007; 109:2736.
  45. Meinhardt A, Burkhardt B, Zimmermann M, et al. Phase II window study on rituximab in newly diagnosed pediatric mature B-cell non-Hodgkin's lymphoma and Burkitt leukemia. J Clin Oncol 2010; 28:3115.
  46. Akbayram S, Doğan M, Akgün C, et al. Use of rituximab in three children with relapsed/refractory Burkitt lymphoma. Target Oncol 2010; 5:291.
  47. Goldman S, Smith L, Galardy P, et al. Rituximab with chemotherapy in children and adolescents with central nervous system and/or bone marrow-positive Burkitt lymphoma/leukaemia: a Children's Oncology Group Report. Br J Haematol 2014; 167:394.
  48. Griffin TC, Weitzman S, Weinstein H, et al. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer 2009; 52:177.
  49. Deffenbacher KE, Iqbal J, Sanger W, et al. Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling. Blood 2012; 119:3757.
  50. Oschlies I, Burkhardt B, Salaverria I, et al. Clinical, pathological and genetic features of primary mediastinal large B-cell lymphomas and mediastinal gray zone lymphomas in children. Haematologica 2011; 96:262.
  51. Seidemann K, Tiemann M, Lauterbach I, et al. Primary mediastinal large B-cell lymphoma with sclerosis in pediatric and adolescent patients: treatment and results from three therapeutic studies of the Berlin-Frankfurt-Münster Group. J Clin Oncol 2003; 21:1782.
  52. Gerrard M, Waxman IM, Sposto R, et al. Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy. Blood 2013; 121:278.
  53. Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med 2013; 368:1408.
  54. http://clinicaltrials.gov/show/NCT01516567 (Accessed on February 22, 2013).
  55. Seidemann K, Tiemann M, Henze G, et al. Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency: analysis of 19 patients from the BFM trials. Med Pediatr Oncol 1999; 33:536.
  56. Biggar RJ, Frisch M, Goedert JJ. Risk of cancer in children with AIDS. AIDS-Cancer Match Registry Study Group. JAMA 2000; 284:205.
  57. Schober T, Framke T, Kreipe H, et al. Characteristics of early and late PTLD development in pediatric solid organ transplant recipients. Transplantation 2013; 95:240.
  58. Jaglowski SM, Linden E, Termuhlen AM, Flynn JM. Lymphoma in adolescents and young adults. Semin Oncol 2009; 36:381.
  59. Hochberg J, Waxman IM, Kelly KM, et al. Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma: state of the science. Br J Haematol 2009; 144:24.
  60. Sandlund JT, Guillerman RP, Perkins SL, et al. International Pediatric Non-Hodgkin Lymphoma Response Criteria. J Clin Oncol 2015; 33:2106.
  61. Bakhshi S, Radhakrishnan V, Sharma P, et al. Pediatric nonlymphoblastic non-Hodgkin lymphoma: baseline, interim, and posttreatment PET/CT versus contrast-enhanced CT for evaluation--a prospective study. Radiology 2012; 262:956.