Burkitt Lymphoma

  • Kieron DunleavyEmail author
  • Martine Chamuleau
Part of the Hematologic Malignancies book series (HEMATOLOGIC)


Burkitt lymphoma (BL) is a very rare and highly aggressive B-cell lymphoma. Due to its rarity and high curability, advancing therapeutics in this disease has been challenging. While the central role of MYC in BL has been appreciated for some time, recently, several new mutations that cooperate with MYC and have critical roles in lymphomagenesis have been identified. This potentially paves the way for novel drug development in this disease. Treatment-related toxicity is one of the major therapeutic challenges in BL and frequently leads to discontinuation of treatment, especially in adults and immunosuppressed patients. Recently, intermediate intensity approaches have been tested in this disease, and early results demonstrate good tolerance while maintaining high cure rates in all patient groups.


Burkitt lymphoma MYC TCF3 CCND3 ID3 Risk-adapted Endemic Sporadic HIV-associated EBV 


  1. 1.
    Burkitt D. A sarcoma involving the jaws in African children. Br J Surg. 1958;46(197):218–23.CrossRefGoogle Scholar
  2. 2.
    Kelly GL, Rickinson AB. Burkitt lymphoma: revisiting the pathogenesis of a virus-associated malignancy. Hematology Am Soc Hematol Educ Program. 2007:277–84.Google Scholar
  3. 3.
    Heslop HE. Biology and treatment of Epstein-Barr virus-associated non-Hodgkin lymphomas. Hematology Am Soc Hematol Educ Program. 2005:260–6.Google Scholar
  4. 4.
    Shimizu N, Tanabe-Tochikura A, Kuroiwa Y, Takada K. Isolation of Epstein-Barr virus (EBV)-negative cell clones from the EBV-positive Burkitt’s lymphoma (BL) line Akata: malignant phenotypes of BL cells are dependent on EBV. J Virol. 1994;68(9):6069–73.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Komano J, Sugiura M, Takada K. Epstein-Barr virus contributes to the malignant phenotype and to apoptosis resistance in Burkitt’s lymphoma cell line Akata. J Virol. 1998;72(11):9150–6.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Kamranvar SA, Gruhne B, Szeles A, Masucci MG. Epstein-Barr virus promotes genomic instability in Burkitt’s lymphoma. Oncogene. 2007;26(35):5115–23.CrossRefGoogle Scholar
  7. 7.
    Kelly GL, Milner AE, Baldwin GS, Bell AI, Rickinson AB. Three restricted forms of Epstein-Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 2006;103(40):14935–40.CrossRefGoogle Scholar
  8. 8.
    Robbiani DF, Deroubaix S, Feldhahn N, Oliveira TY, Callen E, Wang Q, et al. Plasmodium infection promotes genomic instability and AID-dependent B cell lymphoma. Cell. 2015;162(4):727–37.CrossRefGoogle Scholar
  9. 9.
    Rochford R, Cannon MJ, Moormann AM. Endemic Burkitt’s lymphoma: a polymicrobial disease? Nat Rev Microbiol. 2005;3(2):182–7.CrossRefGoogle Scholar
  10. 10.
    Chene A, Donati D, Orem J, Mbidde ER, Kironde F, Wahlgren M, et al. Endemic Burkitt’s lymphoma as a polymicrobial disease: new insights on the interaction between Plasmodium falciparum and Epstein-Barr virus. Semin Cancer Biol. 2009;19(6):411–20.CrossRefGoogle Scholar
  11. 11.
    Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982;79(24):7824–7.CrossRefGoogle Scholar
  12. 12.
    Burotto M, Berkovits A, Dunleavy K. Double hit lymphoma: from biology to therapeutic implications. Expert Rev Hematol. 2016;9(7):669–78.CrossRefGoogle Scholar
  13. 13.
    Lenze D, Leoncini L, Hummel M, Volinia S, Liu CG, Amato T, et al. The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma. Leukemia. 2011;25(12):1869–76.CrossRefGoogle Scholar
  14. 14.
    Piccaluga PP, De Falco G, Kustagi M, Gazzola A, Agostinelli C, Tripodo C, et al. Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes. Blood. 2011;117(13):3596–608.CrossRefGoogle Scholar
  15. 15.
    Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490(7418):116–20.CrossRefGoogle Scholar
  16. 16.
    Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, et al. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012;44(12):1321–5.CrossRefGoogle Scholar
  17. 17.
    Richter J, Schlesner M, Hoffmann S, Kreuz M, Leich E, Burkhardt B, et al. Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nat Genet. 2012;44(12):1316–20.CrossRefGoogle Scholar
  18. 18.
    Rohde M, Bonn BR, Zimmermann M, Lange J, Moricke A, Klapper W, et al. Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the non-Hodgkin lymphoma Berlin-Frankfurt-Munster protocols. Haematologica. 2017;102(6):1091–8.CrossRefGoogle Scholar
  19. 19.
    Campo E. New pathogenic mechanisms in Burkitt lymphoma. Nat Genet. 2012;44(12):1288–9.CrossRefGoogle Scholar
  20. 20.
    Dave SS, Fu K, Wright GW, Lam LT, Kluin P, Boerma EJ, et al. Molecular diagnosis of Burkitt’s lymphoma. N Engl J Med. 2006;354(23):2431–42.CrossRefGoogle Scholar
  21. 21.
    Hummel M, Bentink S, Berger H, Klapper W, Wessendorf S, Barth TF, et al. A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling. N Engl J Med. 2006;354(23):2419–30.CrossRefGoogle Scholar
  22. 22.
    Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.CrossRefGoogle Scholar
  23. 23.
    Salaverria I, Martin-Guerrero I, Wagener R, Kreuz M, Kohler CW, Richter J, et al. A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma. Blood. 2014;123(8):1187–98.CrossRefGoogle Scholar
  24. 24.
    Ferreiro JF, Morscio J, Dierickx D, Marcelis L, Verhoef G, Vandenberghe P, et al. Post-transplant molecularly defined Burkitt lymphomas are frequently MYC-negative and characterized by the 11q-gain/loss pattern. Haematologica. 2015;100(7):e275–9.CrossRefGoogle Scholar
  25. 25.
    Castillo JJ, Nadeem O. Improving the accuracy in prognosis for Burkitt lymphoma patients. Expert Rev Anticancer Ther. 2014;14(2):125–7.CrossRefGoogle Scholar
  26. 26.
    Castillo JJ, Winer ES, Olszewski AJ. Population-based prognostic factors for survival in patients with Burkitt lymphoma: an analysis from the surveillance, epidemiology, and end results database. Cancer. 2013;119(20):3672–9.CrossRefGoogle Scholar
  27. 27.
    Wasterlid T, Brown PN, Hagberg O, Hagberg H, Pedersen LM, D’Amore F, et al. Impact of chemotherapy regimen and rituximab in adult Burkitt lymphoma: a retrospective population-based study from the Nordic Lymphoma Group. Ann Oncol. 2013;24(7):1879–86.CrossRefGoogle Scholar
  28. 28.
    Wasterlid T, Jonsson B, Hagberg H, Jerkeman M. Population based study of prognostic factors and treatment in adult Burkitt lymphoma: a Swedish Lymphoma Registry study. Leuk Lymphoma. 2011;52(11):2090–6.CrossRefGoogle Scholar
  29. 29.
    Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, et al. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt’s lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002;13(8):1264–74.CrossRefGoogle Scholar
  30. 30.
    Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, et al. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008;112(6):2248–60.CrossRefGoogle Scholar
  31. 31.
    Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, et al. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt’s lymphoma: a retrospective analysis. Ann Oncol. 2011;22(8):1859–64.CrossRefGoogle Scholar
  32. 32.
    Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369(20):1915–25.CrossRefGoogle Scholar
  33. 33.
    Gerrard M, Cairo MS, Weston C, Auperin A, Pinkerton R, Lambilliote A, 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(6):840–7.CrossRefGoogle Scholar
  34. 34.
    Corazzelli G, Frigeri F, Russo F, Frairia C, Arcamone M, Esposito G, et al. RD-CODOX-M/IVAC with rituximab and intrathecal liposomal cytarabine in adult Burkitt lymphoma and ‘unclassifiable’ highly aggressive B-cell lymphoma. Br J Haematol. 2012;156(2):234–44.CrossRefGoogle Scholar
  35. 35.
    Dunleavy K, Little RF, Wilson WH. Update on Burkitt lymphoma. Hematol Oncol Clin North Am. 2016;30(6):1333–43.CrossRefGoogle Scholar
  36. 36.
    Patte C, Auperin A, Michon J, Behrendt H, Leverger G, Frappaz D, et al. The Societe Francaise d’Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood. 2001;97(11):3370–9.CrossRefGoogle Scholar
  37. 37.
    Divine M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, et al. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005;16(12):1928–35.CrossRefGoogle Scholar
  38. 38.
    Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmermann M, 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.PubMedGoogle Scholar
  39. 39.
    Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, et al. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol Off J Am Soc Clin Oncol. 1996;14(3):925–34.CrossRefGoogle Scholar
  40. 40.
    Thomas DA, Cortes J, O’Brien S, Pierce S, Faderl S, Albitar M, et al. Hyper-CVAD program in Burkitt’s-type adult acute lymphoblastic leukemia. J Clin Oncol Off J Am Soc Clin Oncol. 1999;17(8):2461–70.CrossRefGoogle Scholar
  41. 41.
    Thomas DA, Faderl S, O’Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106(7):1569–80.CrossRefGoogle Scholar
  42. 42.
    Hoelzer D, Walewski J, Dohner H, Viardot A, Hiddemann W, Spiekermann K, et al. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014;124(26):3870–9.CrossRefGoogle Scholar
  43. 43.
    Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, et al. Rituximab and dose-dense chemotherapy for adults with Burkitt’s lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10036):2402–11.CrossRefGoogle Scholar
  44. 44.
    Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, et al. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015;126(2):160–6.CrossRefGoogle Scholar
  45. 45.
    Dunleavy K, Roschewski M, Abramson JS, Link B, Parekh S, Jagadeesh D, et al. Risk-adapted therapy in adults with Burkitt lymphoma: updated results of a multi-center prospective phase II study of DA-EPOCH-R. Hematol Oncol. 2017;35(S2):133–4.CrossRefGoogle Scholar
  46. 46.
    Short NJ, Kantarjian HM, Ko H, Khoury JD, Ravandi F, Thomas DA, et al. Outcomes of adults with relapsed or refractory Burkitt and high-grade B-cell leukemia/lymphoma. Am J Hematol. 2017;92(6):E114–E7.CrossRefGoogle Scholar
  47. 47.
    Sweetenham JW, Pearce R, Taghipour G, Blaise D, Gisselbrecht C, Goldstone AH. Adult Burkitt’s and Burkitt-like non-Hodgkin’s lymphoma—outcome for patients treated with high-dose therapy and autologous stem-cell transplantation in first remission or at relapse: results from the European Group for Blood and Marrow Transplantation. J Clin Oncol. 1996;14(9):2465–72.CrossRefGoogle Scholar
  48. 48.
    Maramattom LV, Hari PN, Burns LJ, Carreras J, Arcese W, Cairo MS, et al. Autologous and allogeneic transplantation for burkitt lymphoma outcomes and changes in utilization: a report from the center for international blood and marrow transplant research. Biology Blood Marrow Transplant. 2013;19(2):173–9.CrossRefGoogle Scholar
  49. 49.
    Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, et al. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood. 2003;101(12):4653–9.CrossRefGoogle Scholar
  50. 50.
    Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013;368(15):1408–16.Google Scholar
  51. 51.
    Kochenderfer JN, Somerville RPT, Lu T, Shi V, Bot A, Rossi J, et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum Interleukin-15 levels. J Clin Oncol. 2017;35(16):1803–13.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.George Washington University Cancer CenterWashingtonUSA
  2. 2.VU University Medical CenterAmsterdamNetherlands

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