Childhood and Adolescence Non-Hodgkin Lymphomas in Low- and Middle-Income Countries

  • Nmazuo W. Ozuah
  • Nader Kim El-MallawanyEmail author


While it is estimated that 80% of childhood cancers occur in low- and middle-income countries (LMIC), the non-Hodgkin lymphomas (NHL) of childhood and adolescence are among the five most common pediatric malignancies worldwide. Recent epidemiological data have demonstrated that the incidence of NHL is significantly higher in many regions throughout the LMIC of the world, with the highest incidence found in the equatorial belt of sub-Saharan Africa, where Burkitt lymphoma (BL) is the most common childhood cancer overall. Other distinct epidemiological features of pediatric NHL in LMIC include the relationship of Epstein–Barr virus (EBV) and malaria to endemic Burkitt lymphoma in Africa, as well as the distinct predominance of EBV-associated T- and NK-cell NHL in Central and South America plus East Asia. This chapter will describe some of the unique patterns of childhood and adolescence NHL in LMIC as well as review clinical data from sub-Saharan Africa and Central and South America. The collective experience of treating pediatric NHL in LMIC highlights the challenges of matching the exceptionally high cure rates achieved in high-income countries amid the limitations in medical resources that persist in LMIC. More precise determinations of the true epidemiology of pediatric NHL in LMIC are needed, as well as adapted treatment protocols that can be safely and effectively delivered across the heterogeneous circumstances worldwide. Improved medical and societal infrastructure and increased multidisciplinary subspecialty expertise are required to bridge the gap between disparate survival outcomes that exist between high income and LMIC. Ultimately, there is a great opportunity to capitalize on the potential for excellent survival outcomes in pediatric NHL and provide curative therapy for all children with NHL across the globe.


Non-Hodgkin lymphoma NHL Pediatric oncology Global health Low- and middle-income countries LMIC Africa South America Central America EBV 


  1. 1.
    Gross TG, Biondi A. Paediatric non-Hodgkin lymphoma in low and middle income countries. Br J Haematol. 2016;173(4):651–4.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Burkitt DP. Epidemiology of Burkitt’s lymphoma. Proc R Soc Med. 1971;64(9):909–10.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Magrath I. Epidemiology: clues to the pathogenesis of Burkitt lymphoma. Br J Haematol. 2012;156(6):744–56.PubMedCrossRefGoogle Scholar
  4. 4.
    van den Bosch CA. Is endemic Burkitt’s lymphoma an alliance between three infections and a tumour promoter? Lancet Oncol. 2004;5(12):738–46.PubMedCrossRefGoogle Scholar
  5. 5.
    Dojcinov SD, Fend F, Quintanilla-Martinez L. EBV-positive lymphoproliferations of B- T- and NK-cell derivation in non-immunocompromised hosts. Pathogens. 2018;7(1):28.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Haverkos BM, Pan Z, Gru AA, Freud AG, Rabinovitch R, Xu-Welliver M, et al. Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT): an update on epidemiology, clinical presentation, and natural history in North American and European cases. Curr Hematol Malig Rep. 2016;11(6):514–27.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Quintanilla-Martinez L, Kumar S, Fend F, Reyes E, Teruya-Feldstein J, Kingma DW, et al. Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood. 2000;96(2):443–51.PubMedGoogle Scholar
  8. 8.
    Iwanaga M, Watanabe T, Yamaguchi K. Adult T-cell leukemia: a review of epidemiological evidence. Front Microbiol. 2012;3:322.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Dollard SC, Butler LM, Jones AM, Mermin JH, Chidzonga M, Chipato T, et al. Substantial regional differences in human herpesvirus 8 seroprevalence in sub-Saharan Africa: insights on the origin of the “Kaposi’s sarcoma belt”. Int J Cancer. 2010;127(10):2395–401.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Orem J, Otieno MW, Remick SC. AIDS-associated cancer in developing nations. Curr Opin Oncol. 2004;16(5):468–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Linet MS, Brown LM, Mbulaiteye SM, Check D, Ostroumova E, Landgren A, et al. International long-term trends and recent patterns in the incidence of leukemias and lymphomas among children and adolescents ages 0-19 years. Int J Cancer. 2016;138(8):1862–74.PubMedCrossRefGoogle Scholar
  12. 12.
    Burkitt D, O’Conor GT. Malignant lymphoma in African children. I. A clinical syndrome. Cancer. 1961;14:258–69.PubMedCrossRefGoogle Scholar
  13. 13.
    Orem J, Sandin S, Weibull CE, Odida M, Wabinga H, Mbidde E, et al. Agreement between diagnoses of childhood lymphoma assigned in Uganda and by an international reference laboratory. Clin Epidemiol. 2012;4:339–47.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Ogwang MD, Zhao W, Ayers LW, Mbulaiteye SM. Accuracy of Burkitt lymphoma diagnosis in constrained pathology settings: importance to epidemiology. Arch Pathol Lab Med. 2011;135(4):445–50.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Naresh KN, Raphael M, Ayers L, Hurwitz N, Calbi V, Rogena E, et al. Lymphomas in sub-Saharan Africa--what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research? Br J Haematol. 2011;154(6):696–703.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    El-Mallawany NK, Mutai M, Mtete I, Gopal S, Stanley CC, Wasswa P, et al. Beyond Endemic Burkitt Lymphoma: navigating challenges of differentiating childhood lymphoma diagnoses amid limitations in pathology resources in Lilongwe, Malawi. Glob Pediatr Health. 2017;4:2333794X17715831.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Molyneux EM, Rochford R, Griffin B, Newton R, Jackson G, Menon G, et al. Burkitt’s lymphoma. Lancet. 2012;379(9822):1234–44.PubMedCrossRefGoogle Scholar
  18. 18.
    Moormann AM, Bailey JA. Malaria - how this parasitic infection aids and abets EBV-associated Burkitt lymphomagenesis. Curr Opin Virol. 2016;20:78–84.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Stefan DC, Lutchman R. Burkitt lymphoma: epidemiological features and survival in a South African centre. Infect Agents Cancer. 2014;9:19.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Piriou E, Asito AS, Sumba PO, Fiore N, Middeldorp JM, Moormann AM, et al. Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the etiology of endemic Burkitt lymphoma. J Infect Dis. 2012;205(6):906–13.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Reynaldi A, Schlub TE, Chelimo K, Sumba PO, Piriou E, Ogolla S, et al. Impact of Plasmodium falciparum coinfection on longitudinal Epstein-Barr virus kinetics in Kenyan children. J Infect Dis. 2016;213(6):985–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Lam KM, Syed N, Whittle H, Crawford DH. Circulating Epstein-Barr virus-carrying B cells in acute malaria. Lancet. 1991;337(8746):876–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964;1(7335):702–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Epstein A. Burkitt lymphoma and the discovery of Epstein-Barr virus. Br J Haematol. 2012;156(6):777–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Davidson A, Hendricks M. Experience with B-cell lymphoma at a South African centre in the HIV Era. Transfus Apher Sci. 2013;49(1):31–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Mutalima N, Molyneux EM, Johnston WT, Jaffe HW, Kamiza S, Borgstein E, et al. Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi - preliminary findings. Infect Agents Cancer. 2010;5(5):1–6.Google Scholar
  27. 27.
    Shiramizu B, Barriga F, Neequaye J, Jafri A, Dalla-Favera R, Neri A, et al. Patterns of chromosomal breakpoint locations in Burkitt’s lymphoma: relevance to geography and Epstein-Barr virus association. Blood. 1991;77(7):1516–26.PubMedGoogle Scholar
  28. 28.
    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.PubMedCrossRefGoogle Scholar
  29. 29.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Kaymaz Y, Oduor CI, Yu H, Otieno JA, Ong’echa JM, Moormann AM, et al. Comprehensive transcriptome and mutational profiling of endemic Burkitt lymphoma reveals EBV type-specific Differences. Mol Cancer Res. 2017;15(5):563–76.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Abate F, Ambrosio MR, Mundo L, Laginestra MA, Fuligni F, Rossi M, et al. Distinct viral and mutational spectrum of endemic Burkitt lymphoma. PLoS Pathog. 2015;11(10):e1005158.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Amato T, Abate F, Piccaluga P, Iacono M, Fallerini C, Renieri A, et al. Clonality analysis of immunoglobulin gene rearrangement by next-generation sequencing in endemic Burkitt lymphoma suggests antigen drive activation of BCR as opposed to sporadic Burkitt lymphoma. Am J Clin Pathol. 2016;145(1):116–27.PubMedCrossRefGoogle Scholar
  33. 33.
    El-Mallawany NK, Day N, Ayello J, Van de Ven C, Conlon K, Fermin D, et al. Differential proteomic analysis of endemic and sporadic Epstein-Barr virus-positive and negative Burkitt lymphoma. Eur J Cancer. 2015;51(1):92–100.PubMedCrossRefGoogle Scholar
  34. 34.
    Thorley-Lawson D, Deitsch KW, Duca KA, Torgbor C. The link between Plasmodium falciparum malaria and endemic Burkitt’s lymphoma-new insight into a 50-year-old enigma. PLoS Pathog. 2016;12(1):e1005331.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Park SR. Activation-induced cytidine deaminase in B Cell immunity and cancers. Immune Netw. 2012;12(6):230–9.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Ramiro AR, Jankovic M, Eisenreich T, Difilippantonio S, Chen-Kiang S, Muramatsu M, et al. AID is required for c-myc/IgH chromosome translocations in vivo. Cell. 2004;118(4):431–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Ramiro AR, Jankovic M, Callen E, Difilippantonio S, Chen HT, McBride KM, et al. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature. 2006;440(7080):105–9.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Clybouw C, McHichi B, Mouhamad S, Auffredou MT, Bourgeade MF, Sharma S, et al. EBV infection of human B lymphocytes leads to down-regulation of Bim expression: relationship to resistance to apoptosis. J Immunol. 2005;175(5):2968–73.PubMedCrossRefGoogle Scholar
  39. 39.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Kelly GL, Milner AE, Tierney RJ, Croom-Carter DS, Altmann M, Hammerschmidt W, et al. Epstein-Barr virus nuclear antigen 2 (EBNA2) gene deletion is consistently linked with EBNA3A, -3B, and -3C expression in Burkitt’s lymphoma cells and with increased resistance to apoptosis. J Virol. 2005;79(16):10709–17.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Kennedy G, Komano J, Sugden B. Epstein-Barr virus provides a survival factor to Burkitt’s lymphomas. Proc Natl Acad Sci U S A. 2003;100(24):14269–74.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Komano J, Maruo S, Kurozumi K, Oda T, Takada K. Oncogenic role of Epstein-Barr virus-encoded RNAs in Burkitt’s lymphoma cell line Akata. J Virol. 1999;73(12):9827–31.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Nanbo A, Inoue K, Adachi-Takasawa K, Takada K. Epstein-Barr virus RNA confers resistance to interferon-alpha-induced apoptosis in Burkitt’s lymphoma. EMBO J. 2002;21(5):954–65.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Ruf IK, Rhyne PW, Yang C, Cleveland JL, Sample JT. Epstein-Barr virus small RNAs potentiate tumorigenicity of Burkitt lymphoma cells independently of an effect on apoptosis. J Virol. 2000;74(21):10223–8.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Njie R, Bell AI, Jia H, Croom-Carter D, Chaganti S, Hislop AD, et al. The effects of acute malaria on Epstein-Barr virus (EBV) load and EBV-specific T cell immunity in Gambian children. J Infect Dis. 2009;199(1):31–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Whittle HC, Brown J, Marsh K, Greenwood BM, Seidelin P, Tighe H, et al. T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria. Nature. 1984;312(5993):449–50.PubMedCrossRefGoogle Scholar
  47. 47.
    Moormann AM, Chelimo K, Sumba OP, Lutzke ML, Ploutz-Snyder R, Newton D, et al. Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children. J Infect Dis. 2005;191(8):1233–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Ogwang MD, Bhatia K, Biggar RJ, Mbulaiteye SM. Incidence and geographic distribution of endemic Burkitt lymphoma in northern Uganda revisited. Int J Cancer. 2008;123(11):2658–63.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Orem J, Mulumba Y, Algeri S, Bellocco R, Mangen FW, Mbidde EK, et al. Clinical characteristics, treatment and outcome of childhood Burkitt’s lymphoma at the Uganda Cancer Institute. Trans R Soc Trop Med Hyg. 2011;105(12):717–26.PubMedCrossRefGoogle Scholar
  50. 50.
    Offor UT, Akyea RK, Neequaye JE, Renner LA, Segbefia CI. The changing clinical pattern of endemic Burkitt lymphoma in Western Africa: experience from a tertiary center in Ghana. Pediatr Blood Cancer. 2018;65:e27275.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Stanley CC, Westmoreland KD, Heimlich BJ, El-Mallawany NK, Wasswa P, Mtete I, et al. Outcomes for paediatric Burkitt lymphoma treated with anthracycline-based therapy in Malawi. Br J Haematol. 2016;173(5):705–12.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Walusansa V, Okuku F, Orem J. Burkitt lymphoma in Uganda, the legacy of Denis Burkitt and an update on the disease status. Br J Haematol. 2012;156(6):757–60.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Depani S, Banda K, Bailey S, Israels T, Chagaluka G, Molyneux E. Outcome is unchanged by adding vincristine upfront to the Malawi 28-day protocol for endemic Burkitt lymphoma. Pediatr Blood Cancer. 2015;62(11):1929–34.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    El-Mallawany NK, Cairo MS. Advances in the diagnosis and treatment of childhood and adolescent B-cell non-Hodgkin lymphoma. Clin Adv Hematol Oncol. 2015;13(2):113–23.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Miles RR, Arnold S, Cairo MS. Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia. Br J Haematol. 2012;156(6):730–43.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Anderson JR, Jenkin RD, Wilson JF, Kjeldsberg CR, Sposto R, Chilcote RR, et al. Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin’s lymphoma: a report of CCG-551 from the Childrens Cancer Group. J Clin Oncol Off J Am Soc Clin Oncol. 1993;11(6):1024–32.CrossRefGoogle Scholar
  57. 57.
    Tubergen DG, Krailo MD, Meadows AT, Rosenstock J, Kadin M, Morse M, et al. Comparison of treatment regimens for pediatric lymphoblastic non-Hodgkin’s lymphoma: a Childrens Cancer Group study. J Clin Oncol Off J Am Soc Clin Oncol. 1995;13(6):1368–76.CrossRefGoogle Scholar
  58. 58.
    Murphy SB. Classification, staging and end results of treatment of childhood non-Hodgkin’s lymphomas: dissimilarities from lymphomas in adults. Semin Oncol. 1980;7(3):332–9.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Burkitt D, Hutt MS, Wright DH. The African lymphoma: preliminary observations on response to therapy. Cancer. 1965;18:399–410.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Ziegler JL, Morrow RH Jr, Fass L, Kyalwazi SK, Carbone PP. Treatment of Burkitt’s tumor with cyclophosphamide. Cancer. 1970;26(2):474–84.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Nkrumah FK, Perkins IV. Burkitt’s lymphoma: a clinical study of 110 patients. Cancer. 1976;37(2):671–6.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Olweny CL, Katongole-Mbidde E, Otim D, Lwanga SK, Magrath IT, Ziegler JL. Long-term experience with Burkitt’s lymphoma in Uganda. Int J Cancer. 1980;26(3):261–6.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Kazembe P, Hesseling PB, Griffin BE, Lampert I, Wessels G. Long term survival of children with Burkitt lymphoma in Malawi after cyclophosphamide monotherapy. Med Pediatr Oncol. 2003;40(1):23–5.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Traore F, Coze C, Atteby JJ, Andre N, Moreira C, Doumbe P, et al. Cyclophosphamide monotherapy in children with Burkitt lymphoma: a study from the French-African Pediatric Oncology Group (GFAOP). Pediatr Blood Cancer. 2011;56(1):70–6.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Marjerrison S, Fernandez CV, Price VE, Njume E, Hesseling P. The use of ultrasound in endemic Burkitt lymphoma in Cameroon. Pediatr Blood Cancer. 2012;58(3):352–5.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Cairo MS, Sposto R, Gerrard M, Auperin A, Goldman SC, Harrison L, 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 Off J Am Soc Clin Oncol. 2012;30(4):387–93.CrossRefGoogle Scholar
  67. 67.
    Ngoma T, Adde M, Durosinmi M, Githang’a J, Aken’Ova Y, Kaijage J, et al. Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease. Br J Haematol. 2012;158(6):749–62.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Buckle G, Maranda L, Skiles J, Ong’echa JM, Foley J, Epstein M, et al. Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: a historical cohort study. Int J Cancer. 2016;139(6):1231–40.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Molyneux E, Schwalbe E, Chagaluka G, Banda K, Israels T, Depani S, et al. The use of anthracyclines in the treatment of endemic Burkitt lymphoma. Br J Haematol. 2017;177(6):984–90.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Westmoreland KD, El-Mallawany NK, Kazembe P, Stanley CC, Gopal S. Dissecting heterogeneous outcomes for paediatric Burkitt lymphoma in Malawi after anthracycline-based treatment. Br J Haematol. 2017;181:853–4.PubMedCrossRefGoogle Scholar
  71. 71.
    Harif M, Barsaoui S, Benchekroun S, Bouhas R, Doumbe P, Khattab M, et al. Treatment of B-cell lymphoma with LMB modified protocols in Africa--report of the French-African Pediatric Oncology Group (GFAOP). Pediatr Blood Cancer. 2008;50(6):1138–42.PubMedCrossRefGoogle Scholar
  72. 72.
    Hesseling P, Broadhead R, Mansvelt E, Louw M, Wessels G, Borgstein E, et al. The 2000 Burkitt lymphoma trial in Malawi. Pediatr Blood Cancer. 2005;44(3):245–50.PubMedCrossRefGoogle Scholar
  73. 73.
    Goldman S, Smith L, Anderson JR, Perkins S, Harrison L, Geyer MB, 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.PubMedCrossRefGoogle Scholar
  74. 74.
    Meinhardt A, Burkhardt B, Zimmermann M, Borkhardt A, Kontny U, Klingebiel T, 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 Off J Am Soc Clin Oncol. 2010;28(19):3115–21.CrossRefGoogle Scholar
  75. 75.
    Montgomery ND, Liomba NG, Kampani C, Krysiak R, Stanley CC, Tomoka T, et al. Accurate real-time diagnosis of lymphoproliferative disorders in Malawi through clinicopathologic teleconferences: a model for pathology services in sub-Saharan Africa. Am J Clin Pathol. 2016;146(4):423–30.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Rees CA, Keating EM, Lukolyo H, Danysh HE, Scheurer ME, Mehta PS, et al. Mapping the epidemiology of Kaposi Sarcoma and non-Hodgkin lymphoma among children in sub-Saharan Africa: a review. Pediatr Blood Cancer. 2016;63(8):1325–31.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Martro E, Bulterys M, Stewart JA, Spira TJ, Cannon MJ, Thacher TD, et al. Comparison of human herpesvirus 8 and Epstein-Barr virus seropositivity among children in areas endemic and non-endemic for Kaposi’s sarcoma. J Med Virol. 2004;72(1):126–31.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Tukei V, Kekitiinwa A, Beasley R. Prevalence and outcome of HIV-associated malignancis among children. AIDS. 2011;25:1789–93.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    El-Mallawany NK, Wasswa P, Mtete I, Mutai M, Stanley CC, Mtunda M, et al. Identifying opportunities to bridge disparity gaps in curing childhood cancer in Malawi: malignancies with excellent curative potential account for the majority of diagnoses. Pediatr Hematol Oncol. 2017;34(5):261–74.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Chadburn A, Said J, Gratzinger D, Chan JK, de Jong D, Jaffe ES, et al. HHV8/KSHV-positive lymphoproliferative disorders and the spectrum of plasmablastic and plasma cell neoplasms: 2015 SH/EAHP workshop report-part 3. Am J Clin Pathol. 2017;147(2):171–87.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Gopal S, Liomba NG, Montgomery ND, Moses A, Kaimila B, Nyasosela R, et al. Characteristics and survival for HIV-associated multicentric Castleman disease in Malawi. J Int AIDS Soc. 2015;18:20122.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Valsecchi MG, Tognoni G, Bonilla M, Moreno N, Baez F, Pacheco C, et al. Clinical epidemiology of childhood cancer in Central America and Caribbean countries. Ann Oncol. 2004;15(4):680–5.PubMedCrossRefGoogle Scholar
  83. 83.
    Pribnow AK, Ortiz R, Baez LF, Mendieta L, Luna-Fineman S. Effects of malnutrition on treatment-related morbidity and survival of children with cancer in Nicaragua. Pediatr Blood Cancer. 2017;64(11):e26590.CrossRefGoogle Scholar
  84. 84.
    Laurini JA, Perry AM, Boilesen E, Diebold J, Maclennan KA, Muller-Hermelink HK, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood. 2012;120(24):4795–801.PubMedCrossRefGoogle Scholar
  85. 85.
    Perry AM, Molina-Kirsch H, Nathwani BN, Diebold J, Maclennan KA, Muller-Hermelink HK, et al. Classification of non-Hodgkin lymphomas in Guatemala according to the World Health Organization system. Leuk Lymphoma. 2011;52(9):1681–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Cohen JI, Kimura H, Nakamura S, Ko YH, Jaffe ES. Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008. Ann Oncol. 2009;20(9):1472–82.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, et al. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011;117(22):5835–49.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Kimura H, Cohen JI. Chronic active Epstein-Barr virus disease. Front Immunol. 2017;8:1867.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Bollard CM, Cohen JI. How I treat T cell chronic active Epstein barr virus disease. Blood. 2018;131:2899.PubMedCrossRefGoogle Scholar
  90. 90.
    Ohshima K, Kimura H, Yoshino T, Kim CW, Ko YH, Lee SS, et al. Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD. Pathol Int. 2008;58(4):209–17.PubMedCrossRefGoogle Scholar
  91. 91.
    Chabay PA, Preciado MV. EBV primary infection in childhood and its relation to B-cell lymphoma development: a mini-review from a developing region. Int J Cancer. 2013;133(6):1286–92.PubMedCrossRefGoogle Scholar
  92. 92.
    Balfour HH Jr, Sifakis F, Sliman JA, Knight JA, Schmeling DO, Thomas W. Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States and factors affecting its acquisition. J Infect Dis. 2013;208(8):1286–93.PubMedCrossRefGoogle Scholar
  93. 93.
    Mbulaiteye SM, Pullarkat ST, Nathwani BN, Weiss LM, Rao N, Emmanuel B, et al. Epstein-Barr virus patterns in US Burkitt lymphoma tumors from the SEER residual tissue repository during 1979-2009. APMIS. 2014;122(1):5–15.PubMedCrossRefGoogle Scholar
  94. 94.
    Araujo I, Foss HD, Bittencourt A, Hummel M, Demel G, Mendonca N, et al. Expression of Epstein-Barr virus-gene products in Burkitt’s lymphoma in Northeast Brazil. Blood. 1996;87(12):5279–86.PubMedGoogle Scholar
  95. 95.
    Sandlund JT, Fonseca T, Leimig T, Verissimo L, Ribeiro R, Lira V, et al. Predominance and characteristics of Burkitt lymphoma among children with non-Hodgkin lymphoma in northeastern Brazil. Leukemia. 1997;11(5):743–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Queiroga EM, Gualco G, Weiss LM, Dittmer DP, Araujo I, Klumb CE, et al. Burkitt lymphoma in Brazil is characterized by geographically distinct clinicopathologic features. Am J Clin Pathol. 2008;130(6):946–56.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Klumb CE, Hassan R, De Oliveira DE, De Resende LM, Carrico MK, De Almeida Dobbin J, et al. Geographic variation in Epstein-Barr virus-associated Burkitt’s lymphoma in children from Brazil. Int J Cancer. 2004;108(1):66–70.PubMedCrossRefGoogle Scholar
  98. 98.
    Lara J, Cohen M, De Matteo E, Aversa L, Preciado MV, Chabay P. Epstein-Barr virus (EBV) association and latency profile in pediatric Burkitt’s lymphoma: experience of a single institution in Argentina. J Med Virol. 2014;86(5):845–50.PubMedCrossRefGoogle Scholar
  99. 99.
    Lei H, Li T, Li B, Tsai S, Biggar RJ, Nkrumah F, et al. Epstein-Barr virus from Burkitt Lymphoma biopsies from Africa and South America share novel LMP-1 promoter and gene variations. Sci Rep. 2015;5:16706.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Quintanilla-Martinez L, Ridaura C, Nagl F, Saez-de-Ocariz M, Duran-McKinster C, Ruiz-Maldonado R, et al. Hydroa vacciniforme-like lymphoma: a chronic EBV+ lymphoproliferative disorder with risk to develop a systemic lymphoma. Blood. 2013;122(18):3101–10.PubMedCrossRefGoogle Scholar
  101. 101.
    Rodriguez-Pinilla SM, Barrionuevo C, Garcia J, Martinez MT, Pajares R, Montes-Moreno S, et al. EBV-associated cutaneous NK/T-cell lymphoma: review of a series of 14 cases from peru in children and young adults. Am J Surg Pathol. 2010;34(12):1773–82.PubMedCrossRefGoogle Scholar
  102. 102.
    Barrionuevo C, Anderson VM, Zevallos-Giampietri E, Zaharia M, Misad O, Bravo F, et al. Hydroa-like cutaneous T-cell lymphoma: a clinicopathologic and molecular genetic study of 16 pediatric cases from Peru. Appl Immunohistochem Mol Morphol. 2002;10(1):7–14.PubMedGoogle Scholar
  103. 103.
    El-Mallawany NK, Geller L, Bollard CM, Wistinghausen B, Mussai F, Wayne AS, et al. Long-term remission in a child with refractory EBV(+) hydroa vacciniforme-like T-cell lymphoma through sequential matched EBV(+)-related allogeneic hematopoietic SCT followed by donor-derived EBV-specific cytotoxic T-lymphocyte immunotherapy. Bone Marrow Transplant. 2011;46(5):759–61.PubMedCrossRefGoogle Scholar
  104. 104.
    Jaffe ES, Harris NL, Stein H, Isaacson PG. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood. 2008;112(12):4384–99.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Smith MC, Cohen DN, Greig B, Yenamandra A, Vnencak-Jones C, Thompson MA, et al. The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder. Int J Clin Exp Pathol. 2014;7(9):5738–49.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Sevilla DW, El-Mallawany NK, Emmons FN, Alexander S, Bhagat G, Alobeid B. Spectrum of childhood Epstein-Barr virus-associated T-cell proliferations and bone marrow findings. Pediatr Dev Pathol. 2011;14(1):28–37.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Gualco G, Domeny-Duarte P, Chioato L, Barber G, Natkunam Y, Bacchi CE. Clinicopathologic and molecular features of 122 Brazilian cases of nodal and extranodal NK/T-cell lymphoma, nasal type, with EBV subtyping analysis. Am J Surg Pathol. 2011;35(8):1195–203.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Quintanilla-Martinez L, Franklin JL, Guerrero I, Krenacs L, Naresh KN, Rama-Rao C, et al. Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression. Hum Pathol. 1999;30(7):849–55.PubMedCrossRefGoogle Scholar
  109. 109.
    Yamaguchi M, Suzuki R, Oguchi M. Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type. Blood. 2018;131(23):2528–40.PubMedCrossRefGoogle Scholar
  110. 110.
    Howard SC, Ortiz R, Baez LF, Cabanas R, Barrantes J, Fu L, et al. Protocol-based treatment for children with cancer in low income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)--part II. Pediatr Blood Cancer. 2007;48(4):486–90.PubMedCrossRefGoogle Scholar
  111. 111.
    Klumb CE, Schramm MT, De Resende LM, Carrico MK, Coelho AM, de Meis E, et al. Treatment of children with B-cell non-Hodgkin’s lymphoma in developing countries: the experience of a single center in Brazil. J Pediatr Hematol Oncol. 2004;26(7):462–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Chantada G, Casak S, Alderete D, Zubizarreta P, Gallo G, Muriel FS. Treatment of B-cell malignancies in children with a modified BFM-NHL 90 protocol in Argentina. Med Pediatr Oncol. 2003;41(5):488–90.PubMedCrossRefGoogle Scholar
  113. 113.
    Baez F, Pillon M, Manfredini L, Ocampo E, Mendez G, Ortiz R, et al. Treatment of pediatric non-Hodgkin lymphomas in a country with limited resources: results of the first national protocol in Nicaragua. Pediatr Blood Cancer. 2008;50(1):148–52.PubMedCrossRefGoogle Scholar
  114. 114.
    Acquatella G, Insausti CL, Garcia R, Gomez R, Hernandez M, Carneiro M, et al. Outcome of children with B cell lymphoma in Venezuela with the LMB-89 protocol. Pediatr Blood Cancer. 2004;43(5):580–6.PubMedCrossRefGoogle Scholar
  115. 115.
    Navarrete M, Rossi E, Brivio E, Carrillo JM, Bonilla M, Vasquez R, et al. Treatment of childhood acute lymphoblastic leukemia in central America: a lower-middle income countries experience. Pediatr Blood Cancer. 2014;61(5):803–9.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Chagaluka G, Carey P, Banda K, Schwab C, Chilton L, Schwalbe E, et al. Treating childhood acute lymphoblastic leukemia in Malawi. Haematologica. 2013;98(1):e1–3.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Kersten E, Scanlan P, Dubois SG, Matthay KK. Current treatment and outcome for childhood acute leukemia in Tanzania. Pediatr Blood Cancer. 2013;60(12):2047–53.PubMedCrossRefGoogle Scholar
  118. 118.
    Rubagumya F, Xu MJ, May L, Driscoll C, Uwizeye FR, Shyirambere C, et al. Outcomes of low-intensity treatment of acute lymphoblastic leukemia at Butaro Cancer Center of Excellence in Rwanda. J Glob Oncol. 2018;2018(4):1–11.Google Scholar
  119. 119.
    Ceppi F, Ortiz R, Antillon F, Vasquez R, Gomez W, Gamboa J, et al. Anaplastic large cell lymphoma in Central America: a report from the Central American Association of Pediatric Hematology Oncology (AHOPCA). Pediatr Blood Cancer. 2016;63(1):78–82.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Baylor College of Medicine, Department of Pediatrics, Section of Hematology-OncologyHoustonUSA
  2. 2.Texas Children’s Cancer and Hematology Centers, Baylor College of MedicineGlobal HOPE (Hematology-Oncology Pediatric Excellence)HoustonUSA

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