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Non-Hodgkin Lymphoma in Children

  • B-cell NHL, T-cell NHL and Hodgkin Lymphoma (J Armitage, Section Editor)
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Abstract

The non-Hodgkin lymphomas (NHLs) of childhood include high-grade mature B cell lymphoma [Burkitt lymphoma (BL), diffuse large B cell lymphoma (DLBCL), and primary mediastinal large B cell lymphoma (PMLBCL)], anaplastic large cell lymphoma (ALCL), and lymphoblastic lymphoma (LL). The prognosis for children with NHL is generally excellent, although there are some higher risk groups. In this regard, PMLBCL is generally associated with a poorer outcome than BL or DLBCL of comparable stage. The long-term event-free survival for children with ALCL is approximately 70 %. Novel biological agents, including those that target CD-30 or ALK, may hold promise for improving treatment results. Children with LL are treated with regimens derived from those used to treat acute lymphoblastic leukemia (ALL). Recent biological study of LL may provide insights into revising treatment stratification. The challenge in pediatric NHL, a group that already has a relatively good prognosis, is to improve treatment outcome without increasing concerning late effects.

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References

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  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, 2008.

  2. Sandlund JT, Downing JR, Crist WM. Non-Hodgkin's lymphoma in childhood. N Engl J Med. 1996;334(19):1238–48.

    Article  CAS  PubMed  Google Scholar 

  3. Cairo MS 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(7):2736–43.

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Patte C 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(7):2773–80.

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Reiter A et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90. Blood. 1999;94(10):3294–306.

    CAS  PubMed  Google Scholar 

  6. Woessmann W et al. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95. Blood. 2005;105(3):948–58.

    Article  CAS  PubMed  Google Scholar 

  7. Seidemann K 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-Munster Group. J Clin Oncol. 2003;21(9):1782–9.

    Article  CAS  PubMed  Google Scholar 

  8. Gerrard M, Waxman I, Sposto R, Auperin A, Perkins SL, Goldman S, Harrison L, Pinkerton R, McCarthy, Raphael M, Patte C, Cairo MS. Outcome and pathological classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy. Blood. 2012.

  9. Sandlund JT, Choi JK. Pediatric MLBL: challenges remain. Blood. 2013;121(2):245–6.

    Article  CAS  PubMed  Google Scholar 

  10. Dunleavy K et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013;368(15):1408–16.

    Article  CAS  PubMed  Google Scholar 

  11. Woessmann W et al. Therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013;369(3):282. DA-EPOCH-R appears to be active and well tolerated in children with PMLBCL; a larger cohort and longer follow-up are needed to confirm these findings.

    Article  PubMed  Google Scholar 

  12. Goldman S et al. Rituximab and FAB/LMB 96 chemotherapy in children with stage III/IV B-cell non-Hodgkin lymphoma: a Children's Oncology Group report. Leukemia. 2013;27(5):1174–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Goldman S 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(3):394–401.

    Article  CAS  PubMed  Google Scholar 

  14. Meinhardt A 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(19):3115–21.

    Article  CAS  PubMed  Google Scholar 

  15. Seidemann K 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-Munster Group Trial NHL-BFM 90. Blood. 2001;97(12):3699–706.

    Article  CAS  PubMed  Google Scholar 

  16. Laver JH et al. Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non-Hodgkin's lymphoma: a Pediatric Oncology Group study. Leuk Lymphoma. 2002;43(1):105–9.

    Article  PubMed  Google Scholar 

  17. Laver JH 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(3):541–7.

    Article  CAS  PubMed  Google Scholar 

  18. Brugieres L et al. CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood. 1998;92(10):3591–8.

    CAS  PubMed  Google Scholar 

  19. Williams DM et al. Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on the United Kingdom Children's Cancer Study Group chemotherapy regimens. Br J Haematol. 2002;117(4):812–20.

    Article  CAS  PubMed  Google Scholar 

  20. Brugieres L et al. Impact of the methotrexate administration dose on the need for intrathecal treatment in children and adolescents with anaplastic large-cell lymphoma: results of a randomized trial of the EICNHL Group. J Clin Oncol. 2009;27(6):897–903.

    Article  CAS  PubMed  Google Scholar 

  21. Sandlund JT et al. Clinical features and treatment outcome for children with CD30+ large-cell non-Hodgkin's lymphoma. J Clin Oncol. 1994;12(5):895–8.

    CAS  PubMed  Google Scholar 

  22. Brugieres L 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(30):5056–61.

    Article  CAS  PubMed  Google Scholar 

  23. Le Deley MC 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(25):3987–93.

    Article  PubMed  Google Scholar 

  24. Alexander 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(12):2236–42.

    Article  CAS  PubMed  Google Scholar 

  25. Younes A et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363(19):1812–21.

    Article  CAS  PubMed  Google Scholar 

  26. Mosse YP 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(6):472–80. Crizotinib is active and well tolerated in children with ALK+ ALCL.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Damm-Welk C et al. Flow cytometric detection of circulating tumour cells in nucleophosmin/anaplastic lymphoma kinase-positive anaplastic large cell lymphoma: comparison with quantitative polymerase chain reaction. Br J Haematol. 2007;138(4):459–66.

    Article  CAS  PubMed  Google Scholar 

  28. Mussolin L et al. Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis. Leukemia. 2013;27(2):416–22. MDD and ALK antibody levels at diagnosis have prognostic significance in children with ALCL.

    Article  CAS  PubMed  Google Scholar 

  29. Damm-Welk C et al. Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma. Blood. 2014;123(3):334–7. MRD and MDD can be used to identify children with ALCL who are at very high risk of relapse.

    Article  CAS  PubMed  Google Scholar 

  30. Reiter A 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(2):416–21.

    CAS  PubMed  Google Scholar 

  31. Burkhardt B 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(3):491–9.

    Article  PubMed  Google Scholar 

  32. Sandlund JT et al. Effective treatment of advanced-stage childhood lymphoblastic lymphoma without prophylactic cranial irradiation: results of St Jude NHL13 study. Leukemia. 2009;23(6):1127–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Asselin BL et al. Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood. 2011;118(4):874–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Sandlund JT et al. Results of treatment of advanced-stage lymphoblastic lymphoma at St Jude Children's Research Hospital from 1962 to 2002. Ann Oncol. 2013.

  35. Coustan-Smith E et al. Minimal disseminated disease in childhood T-cell lymphoblastic lymphoma: a report from the Children's Oncology Group. J Clin Oncol. 2009;27(21):3533–9.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Bonn BR et al. Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence. Blood. 2013;121(16):3153–60.

    Article  CAS  PubMed  Google Scholar 

  37. Bonn BR et al. Whole exome sequencing hints at a unique mutational profile of paediatric T-cell lymphoblastic lymphoma. Br J Haematol. 2015;168(2):308–13.

    Article  CAS  PubMed  Google Scholar 

  38. Gerrard M 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(2):278–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Lipshultz SE et al. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation. 2013;128(17):1927–95.

    Article  PubMed  Google Scholar 

  40. Coiffier B et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–42.

    Article  CAS  PubMed  Google Scholar 

  41. Hiddemann W et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106(12):3725–32.

    Article  CAS  PubMed  Google Scholar 

  42. Pro B et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30(18):2190–6.

    Article  CAS  PubMed  Google Scholar 

  43. Rimokh R et al. A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ('Ki-1 lymphoma'). Br J Haematol. 1989;71(1):31–6.

    Article  CAS  PubMed  Google Scholar 

  44. Kaneko Y et al. A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis. Blood. 1989;73(3):806–13.

    CAS  PubMed  Google Scholar 

  45. Sandlund JT et al. Clinicopathologic features and treatment outcome of children with large-cell lymphoma and the t(2;5)(p23;q35). Blood. 1994;84(8):2467–71.

    CAS  PubMed  Google Scholar 

  46. Morris SW et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science. 1994;263(5151):1281–4. Published erratum appears in Science 1995 Jan 20;267(5196):316-7.

    Article  CAS  PubMed  Google Scholar 

  47. Morris SW et al. Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma. Br J Haematol. 2001;113(2):275–95.

    Article  CAS  PubMed  Google Scholar 

  48. Shiramizu B et al. Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a Children's Oncology Group report. Br J Haematol. 2011;153(6):758–63.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Ait-Tahar K et al. Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk. Blood. 2010;115(16):3314–9.

    Article  CAS  PubMed  Google Scholar 

  50. Sandlund JT, et al. International Pediatric Non-Hodgkin Lymphoma Response Criteria. J Clin Oncol. 2015.

  51. Rosolen A, et al. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol. 2015.

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Acknowledgments

This study was supported in part by a grant from the National Cancer Institute (CA 21765) and by the American Lebanese Syrian Associated Charities (ALSAC) for John T. Sandlund.

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The author declares that he has no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

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Authors and Affiliations

  1. St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    John T. Sandlund

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Correspondence to John T. Sandlund.

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This article is part of the Topical Collection on B-cell NHL, T-cell NHL and Hodgkin Lymphoma

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Sandlund, J.T. Non-Hodgkin Lymphoma in Children. Curr Hematol Malig Rep 10, 237–243 (2015). https://doi.org/10.1007/s11899-015-0277-y

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