Malignancies associated with Epstein-Barr virus: Pathobiology, clinical features, and evolving treatments

Clinical Advances in Hematology and Oncology

Volumn 12, Issue 6, 2014, Pages 358-371

  Neparidze, Natalia ^a   Lacy, Jill ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Burkitt lymphoma; Epstein Barr virus; Gastric cancer; Hodgkin lymphoma; Nasopharyngeal; Post transplant lymphoproliferative disorder

Indexed keywords

4 PHENYLBUTYRIC ACID; 8 [4 (1 AMINOCYCLOBUTYL) PHENYL] 9 PHENYL 1, 2, 4 TRIAZOLO [3, 4 F] [1, 6] NAPHTHYRIDIN 3 (2H) ONE; ARGININE BUTYRATE; ARSENIC TRIOXIDE; AZACITIDINE; BORTEZOMIB; BRENTUXIMAB VEDOTIN; BUTYRIC ACID DERIVATIVE; CYCLOPHOSPHAMIDE; DASATINIB; DEXAMETHASONE; DOXORUBICIN; EPSTEIN BARR VIRUS VACCINE; ETOPOSIDE; GANCICLOVIR; GEMCITABINE; IFOSFAMIDE; LATENT MEMBRANE PROTEIN 1; LATENT MEMBRANE PROTEIN 2; METHOTREXATE; MITOGEN ACTIVATED PROTEIN KINASE; MODIFIED VACCINIA VIRUS ANKARA 5T4 VACCINE; PARTHENOLIDE; RAPAMYCIN; RECOMBINANT EBV GP350; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALGANCICLOVIR; VALPROIC ACID; VINCRISTINE; ZIDOVUDINE;

ANGIOIMMUNOBLASTIC T CELL LYMPHOMA; ARTICLE; BURKITT LYMPHOMA; DONOR LYMPHOCYTE INFUSION; DRUG MEGADOSE; EPSTEIN BARR VIRUS INFECTION; HODGKIN DISEASE; HUMAN; IN SITU HYBRIDIZATION; LARGE CELL LYMPHOMA; LYMPHOMA; LYMPHOMATOID GRANULOMATOSIS; LYMPHOPROLIFERATIVE DISEASE; MALIGNANT NEOPLASTIC DISEASE; NASOPHARYNX CARCINOMA; NK T CELL LYMPHOMA; NONHODGKIN LYMPHOMA; POLYMERASE CHAIN REACTION; PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; PRIMARY INFECTION; STOMACH CANCER; COMPLICATION; EPSTEIN BARR VIRUS; LYMPHOPROLIFERATIVE DISORDERS; NEOPLASMS; PHYSIOLOGY;

EPSTEIN-BARR VIRUS INFECTIONS; HERPESVIRUS 4, HUMAN; HUMANS; LYMPHOPROLIFERATIVE DISORDERS; NEOPLASMS;

EID: 84903514559     PISSN: 15430790     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (163)

1. Saha A, Robertson ES. Epstein-Barr virus-associated B-cell lymphomas: pathogenesis and clinical outcomes. Clin Cancer Res. 2011;17(10):3056-3063.
2. Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene. 2003;22(33):5108-5121.
3. Thorley-Lawson DA, Hawkins JB, Tracy SI, Shapiro M. The pathogenesis of Epstein-Barr virus persistent infection. Curr Opin Virol. 2013;3(3):227-232.
4. Kieff E, Rickinson AB. Epstein-Barr virus and its replication. In: Knipe DN, Howley PM, eds. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.
5. Ersing I, Bernhardt K, Gewurz BE. NF-5B and IRF7 pathway activation by Epstein-Barr virus Latent Membrane Protein 1. Viruses. 2013;5(6):1587-1606.
6. Meij P, van Esser JW, Niesters HG, et al. Impaired recovery of Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes after partially T-depleted allogeneic stem cell transplantation may identify patients at very high risk for progressive EBV reactivation and lymphoproliferative disease. Blood. 2003;101(11):4290-4297.
7. Reddy N, Rezvani K, Barrett AJ, Savani BN. Strategies to prevent EBV reactivation and posttransplant lymphoproliferative disorders (PTLD) after allogeneic stem cell transplantation in high-risk patients. Biol Blood Marrow Transplant. 2011;17(5):591-597.
8. Kwong YL, Pang AW, Leung AY, Chim CS, Tse E. Quantification of circulating Epstein-Barr virus DNA in NK/T-cell lymphoma treated with the SMILE protocol: diagnostic and prognostic significance. Leukemia. 2014;28(4):865-870.
9. Kanakry JA, Li H, Gellert LL, et al. Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial. Blood. 2013;121(18):3547-3553.
10. Hohaus S, Santangelo R, Giachelia M, et al. The viral load of Epstein-Barr virus (EBV) DNA in peripheral blood predicts for biological and clinical characteristics in Hodgkin lymphoma. Clin Cancer Res. 2011;17(9):2885-2892.
11. Wang ZY, Liu QF, Wang H, et al. Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy. Blood. 2012;120(10):2003-2010.
12. Jarrett RF. Risk factors for Hodgkin's lymphoma by EBV status and significance of detection of EBV genomes in serum of patients with EBV-associated Hodgkin's lymphoma. Leuk Lymphoma. 2003;44(S3)(suppl 3):S27-S32.
13. Ito Y, Kimura H, Maeda Y, et al. Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/Tcell lymphoma, nasal type. Clin Cancer Res. 2012;18(15):4183-4190.
14. Cinque P, Cingolani A, Bossolasco S, Antinori A. Positive predictive value of Epstein-Barr virus DNA detection in HIV-related primary central nervous system lymphoma. Clin Infect Dis. 2004;39(9):1396-1397, author reply 1397-1398.
15. Leung SF, Chan KC, Ma BB, et al. Plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma [published online March 17, 2014]. Ann Oncol. 2014. doi:10.1093/ annonc/mdu117.
16. Chan KC, Lo YM. Circulating EBV DNA as a tumor marker for nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):489-496.
17. Bollard CM, Gottschalk S, Torrano V, et al. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol. 2014;32(8):798-808.
18. Yustein JT, Dang CV. Biology and treatment of Burkitt's lymphoma. Curr Opin Hematol. 2007;14(4):375-381.
19. de Leval L, Hasserjian RP. Diffuse large B-cell lymphomas and Burkitt lymphoma. Hematol Oncol Clin North Am. 2009;23(4):791-827.
20. van den Bosch CA. Is endemic Burkitt's lymphoma an alliance between three infections and a tumour promoter? Lancet Oncol. 2004;5(12):738-746.
21. Wright DH. What is Burkitt's lymphoma and when is it endemic? Blood. 1999;93(2):758.
22. Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004;4(10):757-768.
23. Mutalima N, Molyneux E, Jaffe H, et al. Associations between Burkitt lymphoma among children in Malawi and infection with HIV, EBV and malaria: results from a case-control study. PLoS ONE. 2008;3(6):e2505.
24. Allday MJ. How does Epstein-Barr virus (EBV) complement the activation of Myc in the pathogenesis of Burkitt's lymphoma? Semin Cancer Biol. 2009;19(6):366-376.
25. Brady G, Macarthur GJ, Farrell PJ. Epstein-Barr virus and Burkitt lymphoma. Postgrad Med J. 2008;84(993):372-377.
26. Magrath I, Adde M, Shad A, et al. Adults and children with small non-cleavedcell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996;14(3):925-934.
27. Mead GM, Sydes MR, Walewski J, et al; UKLG LY06 collaborators. 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):1264-1274.
28. Mead GM, Barrans SL, Qian W, et al; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. 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):2248-2260.
29. Rizzieri DA, Johnson JL, Niedzwiecki D, et al. Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251. Cancer. 2004;100(7):1438-1448.
30. Thomas DA, Cortes J, O'Brien S, et al. Hyper-CVAD program in Burkitt'stype adult acute lymphoblastic leukemia. J Clin Oncol. 1999;17(8):2461-2470.
31. Smeland S, Blystad AK, Kvaløy SO, et al. Treatment of Burkitt's/Burkittlike lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens. Ann Oncol. 2004;15(7):1072-1078.
32. Bishop PC, Rao VK, Wilson WH. Burkitt's lymphoma: molecular pathogenesis and treatment. Cancer Invest. 2000;18(6):574-583.
33. Bell AI, Groves K, Kelly GL, et al. Analysis of Epstein-Barr virus latent gene expression in endemic Burkitt's lymphoma and nasopharyngeal carcinoma tumour cells by using quantitative real-time PCR assays. J Gen Virol. 2006;87(pt 10):2885-2890.
34. Xue SA, Labrecque LG, Lu QL, et al. Promiscuous expression of Epstein-Barr virus genes in Burkitt's lymphoma from the central African country Malawi. Int J Cancer. 2002;99(5):635-643.
35. Cen O, Longnecker R. Rapamycin reverses splenomegaly and inhibits tumor development in a transgenic model of Epstein-Barr virus-related Burkitt's lymphoma. Mol Cancer Ther. 2011;10(4):679-686.
36. Shirley CM, Chen J, Shamay M, et al. Bortezomib induction of C/EBP/ mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. Blood. 2011;117(23):6297-6303.
37. Li Y, Zhang Y, Fu M, et al. Parthenolide induces apoptosis and lytic cytotoxicity in Epstein-Barr virus-positive Burkitt lymphoma. Mol Med Rep. 2012;6(3):477-482.
38. Thompson S, Messick T, Schultz DC, Reichman M, Lieberman PM. Development of a high-throughput screen for inhibitors of Epstein-Barr virus EBNA1. J Biomol Screen. 2010;15(9):1107-1115.
39. Weiss LM, Strickler JG, Warnke RA, Purtilo DT, Sklar J. Epstein-Barr viral DNA in tissues of Hodgkin's disease. Am J Pathol. 1987;129(1):86-91.
40. Wu TC, Mann RB, Charache P, et al. Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin's disease. Int J Cancer. 1990;46(5):801-804.
41. Kapatai G, Murray P. Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma. J Clin Pathol. 2007;60(12):1342-1349.
42. Alexander FE, Jarrett RF, Lawrence D, et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer. 2000;82(5):1117-1121.
43. Levin LI, Chang ET, Ambinder RF, et al. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma. Blood. 2012;120(18):3750-3755.
44. Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med. 2003;349(14):1324-1332.
45. Chapman AL, Rickinson AB. Epstein-Barr virus in Hodgkin's disease. Ann Oncol. 1998;9(suppl 5):S5-S16.
46. Deacon EM, Pallesen G, Niedobitek G, et al. Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells. J Exp Med. 1993;177(2):339-349.
47. Massini G, Siemer D, Hohaus S. EBV in Hodgkin lymphoma. Mediterr J Hematol Infect Dis. 2009;1(2):e2009013.
48. Kapp U, Yeh WC, Patterson B, et al. Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells. J Exp Med. 1999;189(12):1939-1946.
49. Küppers R. B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. 2003;3(10):801-812.
50. Baumforth KR, Birgersdotter A, Reynolds GM, et al. Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates up-regulation of CCL20 and the migration of regulatory T cells. Am J Pathol. 2008;173(1):195-204.
51. Marshall NA, Culligan DJ, Tighe J, Johnston PW, Barker RN, Vickers MA. The relationships between Epstein-Barr virus latent membrane protein 1 and regulatory T cells in Hodgkin's lymphoma. Exp Hematol. 2007;35(4):596-604.
52. Ansell SM. Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. 2012;87(12):1096-1103.
53. Bollard CM, Aguilar L, Straathof KC, et al. Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's disease. J Exp Med. 2004;200(12):1623-1633.
54. Lucas KG, Salzman D, Garcia A, Sun Q. Adoptive immunotherapy with allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes for recurrent, EBV-positive Hodgkin disease. Cancer. 2004;100(9):1892-1901.
55. Sing AP, Ambinder RF, Hong DJ, et al. Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin's disease. Blood. 1997;89(6):1978-1986.
56. Bierman PJ, Vose JM, Langnas AN, et al. Hodgkin's disease following solid organ transplantation. Ann Oncol. 1996;7(3):265-270.
57. Dharnidharka VR, Douglas VK, Hunger SP, Fennell RS. Hodgkin's lymphoma after post-transplant lymphoproliferative disease in a renal transplant recipient. Pediatr Transplant. 2004;8(1):87-90.
58. Goyal RK, McEvoy L, Wilson DB. Hodgkin disease after renal transplantation in childhood. J Pediatr Hematol Oncol. 1996;18(4):392-395.
59. Garnier JL, Lebranchu Y, Dantal J, et al. Hodgkin's disease after transplantation. Transplantation. 1996;61(1):71-76.
60. Carbone A, Spina M, Gloghini A, Tirelli U. Classical Hodgkin's lymphoma arising in different host's conditions: pathobiology parameters, therapeutic options, and outcome. Am J Hematol. 2011;86(2):170-179.
61. Choquet S, Leblond V, Herbrecht R, et al. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood. 2006;107(8):3053-3057.
62. Chiusolo P, Metafuni E, Cattani P, et al. Prospective evaluation of Epstein-Barr virus reactivation after stem cell transplantation: association with monoclonal gammopathy. J Clin Immunol. 2010;30(6):894-902.
63. Parker A, Bowles K, Bradley JA, et al; Haemato-oncology Task Force of the British Committee for Standards in Haematology and British Transplantation Society. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients-BCSH and BTS Guidelines. Br J Haematol. 2010;149(5):675-692.
64. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019-5032.
65. Gupta S, Fricker FJ, González-Peralta RP, Slayton WB, Schuler PM, Dharnidharka VR. Post-transplant lymphoproliferative disorder in children: recent outcomes and response to dual rituximab/low-dose chemotherapy combination. Pediatr Transplant. 2010;14(7):896-902.
66. Landgren O, Gilbert ES, Rizzo JD, et al. Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation. Blood. 2009;113(20):4992-5001.
67. Cesaro S, Pegoraro A, Tridello G, et al. A prospective study on modulation of immunosuppression for Epstein-Barr virus reactivation in pediatric patients who underwent unrelated hematopoietic stem-cell transplantation. Transplantation. 2010;89(12):1533-1540.
68. Höcker B, Böhm S, Fickenscher H, et al. (Val-)Ganciclovir prophylaxis reduces Epstein-Barr virus primary infection in pediatric renal transplantation. Transpl Int. 2012;25(7):723-731.
69. Shapiro R, Scantlebury VP, Jordan ML, et al. Pediatric renal transplantation under tacrolimus-based immunosuppression. Transplantation. 1999;67(2):299-303.
70. Hou HA, Yao M, Tang JL, et al. Poor outcome in post transplant lymphoproliferative disorder with pulmonary involvement after allogeneic hematopoietic SCT: 13 years' experience in a single institute. Bone Marrow Transplant. 2009;43(4):315-321.
71. Rasche L, Kapp M, Einsele H, Mielke S. EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT. Bone Marrow Transplant. 2014;49(2):163-167.
72. Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH. Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity? Am J Surg Pathol. 2000;24(3):375-385.
73. Buell JF, Gross TG, Hanaway MJ, et al. Posttransplant lymphoproliferative disorder: significance of central nervous system involvement. Transplant Proc. 2005;37(2):954-955.
74. Maecker B, Jack T, Zimmermann M, et al. CNS or bone marrow involvement as risk factors for poor survival in post-transplantation lymphoproliferative disorders in children after solid organ transplantation. J Clin Oncol. 2007;25(31):4902-4908.
75. Xu QS, Ye S, Zhou YQ, Sheng JF, Ye K, Zheng SS. Posttransplantation lymphoproliferative disorder involving the central nervous system in liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2008;7(5):551-554.
76. Twist CJ, Castillo RO. Treatment of recurrent posttransplant lymphoproliferative disorder of the central nervous system with high-dose methotrexate [published online August 1, 2013]. Case Rep Transplant. 2013. doi:1155/2013/765230.
77. Traum AZ, Rodig NM, Pilichowska ME, Somers MJ. Central nervous system lymphoproliferative disorder in pediatric kidney transplant recipients. Pediatr Transplant. 2006;10(4):505-512.
78. Taj MM, Messahel B, Mycroft J, et al. Efficacy and tolerability of high-dose methotrexate in central nervous system positive or relapsed lymphoproliferative disease following liver transplant in children. Br J Haematol. 2008;140(2):191-196.
79. Heslop HE, Slobod KS, Pule MA, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010;115(5):925-935.
80. Comoli P, Labirio M, Basso S, et al. Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood. 2002;99(7):2592-2598.
81. Savoldo B, Goss JA, Hammer MM, et al. Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs). Blood. 2006;108(9):2942-2949.
82. Bollard CM, Rooney CM, Heslop HE. T-cell therapy in the treatment of posttransplant lymphoproliferative disease. Nat Rev Clin Oncol. 2012;9(9):510-519.
83. Doubrovina E, Oflaz-Sozmen B, Prockop SE, et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012;119(11):2644-2656.
84. Ricciardelli I, Brewin J, Lugthart G, Albon SJ, Pule M, Amrolia PJ. Rapid generation of EBV-specific cytotoxic T lymphocytes resistant to calcineurin inhibitors for adoptive immunotherapy. Am J Transplant. 2013;13(12):3244-3252.
85. Barker JN, Doubrovina E, Sauter C, et al. Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using thirdparty EBV-specific cytotoxic T lymphocytes. Blood. 2010;116(23):5045-5049.
86. Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of Epstein-Barr virus (EBV) nuclear antigen 1-specific t cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013;31(1):39-48.
87. Moosmann A, Bigalke I, Tischer J, et al. Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood. 2010;115(14):2960-2970.
88. Gloghini A, Dolcetti R, Carbone A. Lymphomas occurring specifically in HIV-infected patients: from pathogenesis to pathology. Semin Cancer Biol. 2013;23(6):457-467.
89. Mueller N, Mohar A, Evans A, et al. Epstein-Barr virus antibody patterns preceding the diagnosis of non-Hodgkin's lymphoma. Int J Cancer. 1991;49(3):387-393.
90. van Baarle D, Hovenkamp E, Callan MF, et al. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma. Blood. 2001;98(1):146-155.
91. Epeldegui M, Widney DP, Martínez-Maza O. Pathogenesis of AIDS lymphoma: role of oncogenic viruses and B cell activation-associated molecular lesions. Curr Opin Oncol. 2006;18(5):444-448.
92. Piriou ER, van Dort K, Nanlohy NM, Miedema F, van Oers MH, van Baarle D. Altered EBV viral load setpoint after HIV seroconversion is in accordance with lack of predictive value of EBV load for the occurrence of AIDS-related non-Hodgkin lymphoma. J Immunol. 2004;172(11):6931-6937.
93. Richard Y, Amiel C, Jeantils V, et al. Changes in blood B cell phenotypes and Epstein-Barr virus load in chronically human immunodeficiency virus-infected patients before and after antiretroviral therapy. J Infect Dis. 2010;202(9):1424-1434.
94. Kaplan LD, Lee JY, Ambinder RF, et al. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005;106(5):1538-1543.
95. Barta SK, Xue X, Wang D, et al. Treatment factors affecting outcomes in HIVassociated non-Hodgkin lymphomas: a pooled analysis of 1546 patients. Blood. 2013;122(19):3251-3262.
96. Cheah C. Incorporating high-dose IV methotrexate into initial therapy results in lower rates of central nervous system (CNS) relapse in patients with high-risk diffuse large B-cell lymphoma (DLBCL). Paper presented at: 55th ASH Annual Meeting and Exposition; December 7-10, 2013; New Orleans, LA. Abstract 4353.
97. Mentzer SJ, Fingeroth J, Reilly JJ, Perrine SP, Faller DV. Arginine butyrateinduced susceptibility to ganciclovir in an Epstein-Barr-virus-associated lymphoma. Blood Cells Mol Dis. 1998;24(2):114-123.
98. Feng WH, Hong G, Delecluse HJ, Kenney SC. Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol. 2004;78(4):1893-1902.
99. Ghosh SK, Perrine SP, Williams RM, Faller DV. Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents. Blood. 2012;119(4):1008-1017.
100. Perrine SP, Hermine O, Small T, et al. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007;109(6):2571-2578.
101. Kurokawa M, Ghosh SK, Ramos JC, et al. Azidothymidine inhibits NFkappaB and induces Epstein-Barr virus gene expression in Burkitt lymphoma. Blood. 2005;106(1):235-240.
102. Bayraktar UD, Diaz LA, Ashlock B, et al. Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas. Leuk Lymphoma. 2014;55(4):786-794.
103. Boulanger E, Meignin V, Oksenhendler E. Bortezomib (PS-341) in patients with human herpesvirus 8-associated primary effusion lymphoma. Br J Haematol. 2008;141(4):559-561.
104. Granato M, Santarelli R, Lotti LV, et al. JNK and macroautophagy activation by bortezomib has a pro-survival effect in primary effusion lymphoma cells. PLoS ONE. 2013;8(9):e75965.
105. Bhatt S, Ashlock BM, Toomey NL, et al. Efficacious proteasome/HDAC inhibitor combination therapy for primary effusion lymphoma. J Clin Invest. 2013;123(6):2616-2628.
106. Sin SH, Roy D, Wang L, et al. Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Blood. 2007;109(5):2165-2173.
107. Abou-Merhi R, Khoriaty R, Arnoult D, et al. PS-341 or a combination of arsenic trioxide and interferon-alpha inhibit growth and induce caspase-dependent apoptosis in KSHV/HHV-8-infected primary effusion lymphoma cells. Leukemia. 2007;21(8):1792-1801.
108. Bhatt S, Ashlock BM, Natkunam Y, et al. CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma. Blood. 2013;122(7):1233-1242.
109. Stingaciu S, Ticchioni M, Sudaka I, Haudebourg J, Mounier N. Intracavitary cidofovir for human herpes virus-8-associated primary effusion lymphoma in an HIV-negative patient. Clin Adv Hematol Oncol. 2010;8(5):367-374.
110. Halfdanarson TR, Markovic SN, Kalokhe U, Luppi M. A non-chemotherapy treatment of a primary effusion lymphoma: durable remission after intracavitary cidofovir in HIV negative PEL refractory to chemotherapy. Ann Oncol. 2006;17(12):1849-1850.
111. Oyama T, Ichimura K, Suzuki R, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27(1):16-26.
112. Ok CY, Papathomas TG, Medeiros LJ, Young KH. EBV-positive diffuse large B-cell lymphoma of the elderly. Blood. 2013;122(3):328-340.
113. Montes-Moreno S, Odqvist L, Diaz-Perez JA, et al. EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation. Mod Pathol. 2012;25(7):968-982.
114. Oyama T, Yamamoto K, Asano N, et al. Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients. Clin Cancer Res. 2007;13(17):5124-5132.
115. Dunleavy K, Roschewski M, Wilson WH. Lymphomatoid granulomatosis and other Epstein-Barr virus associated lymphoproliferative processes. Curr Hematol Malig Rep. 2012;7(3):208-215.
116. Aoki T, Harada Y, Matsubara E, et al. Long-term remission after multiple relapses in an elderly patient with lymphomatoid granulomatosis after rituximab and high-dose cytarabine chemotherapy without stem-cell transplantation. J Clin Oncol. 2013;31(22):e390-e393.
117. Aozasa K. Pyothorax-associated lymphoma. J Clin Exp Hematop. 2006;46(1):5-10.
118. Nakatsuka S, Yao M, Hoshida Y, Yamamoto S, Iuchi K, Aozasa K. Pyothoraxassociated lymphoma: a review of 106 cases. J Clin Oncol. 2002;20(20):4255-4260.
119. Aozasa K, Takakuwa T, Nakatsuka S. Pyothorax-associated lymphoma: a lymphoma developing in chronic inflammation. Adv Anat Pathol. 2005;12(6):324-331.
120. Narimatsu H, Ota Y, Kami M, et al. Clinicopathological features of pyothorax-associated lymphoma; a retrospective survey involving 98 patients. Ann Oncol. 2007;18(1):122-128.
121. Taniguchi A, Hashida Y, Nemoto Y, Taguchi T, Iwahara Y, Daibata M. Pyothorax-associated lymphoma (PAL) with biclonal Epstein-Barr virus infection: characterization of a novel PAL cell line with unique features. Leuk Res. 2013;37(11):1545-1550.
122. Nakagawa T, Nakano T, Masuda R, et al. Pyothorax-associated lymphoma: complete remission achieved by chemotherapy alone [published online March 29, 2013]. Gen Thorac Cardiovasc Surg. 2013.
123. Krenacs L, Schaerli P, Kis G, Bagdi E. Phenotype of neoplastic cells in angioimmunoblastic T-cell lymphoma is consistent with activated follicular B helper T cells. Blood. 2006;108(3):1110-1111.
124. de Leval L, Rickman DS, Thielen C, et al. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood. 2007;109(11):4952-4963.
125. Weiss LM, Jaffe ES, Liu XF, Chen YY, Shibata D, Medeiros LJ. Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Blood. 1992;79(7):1789-1795.
126. Bräuninger A, Spieker T, Willenbrock K, et al. Survival and clonal expansion of mutating "forbidden" (immunoglobulin receptor-deficient) epstein-barr virus-infected b cells in angioimmunoblastic t cell lymphoma. J Exp Med. 2001;194(7):927-940.
127. Sallah S, Gagnon GA. Angioimmunoblastic lymphadenopathy with dysproteinemia: emphasis on pathogenesis and treatment. Acta Haematol. 1998;99(2):57-64.
128. Federico M, Rudiger T, Bellei M, et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol. 2013;31(2):240-246.
129. Kyriakou C, Canals C, Goldstone A, et al; Outcome-Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Highdose therapy and autologous stem-cell transplantation in angioimmunoblastic lymphoma: complete remission at transplantation is the major determinant of Outcome-Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26(2):218-224.
130. Jaffe ES, Chan JK, Su IJ, et al. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. 1996;20(1):103-111.
131. Rizvi MA, Evens AM, Tallman MS, Nelson BP, Rosen ST. T-cell non-Hodgkin lymphoma. Blood. 2006;107(4):1255-1264.
132. Kimura H, Ito Y, Kawabe S, et al. EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. Blood. 2012;119(3):673-686.
133. Kato S, Miyata T, Takata K, et al. Epstein-Barr virus-positive cytotoxic T-cell lymphoma followed by chronic active Epstein-Barr virus infection-associated T/NKcell lymphoproliferative disorder: a case report. Hum Pathol. 2013;44(12):2849-2852.
134. Li YX, Fang H, Liu QF, et al. Clinical features and treatment outcome of nasaltype NK/T-cell lymphoma of Waldeyer ring. Blood. 2008;112(8):3057-3064.
135. Yamaguchi M, Kwong YL, Kim WS, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol. 2011;29(33):4410-4416.
136. Lung RW, Tong JH, To KF. Emerging roles of small Epstein-Barr virus derived non-coding RNAs in epithelial malignancy. Int J Mol Sci. 2013;14(9):17378-17409.
137. Dawson CW, Port RJ, Young LS. The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin Cancer Biol. 2012;22(2):144-153.
138. Marquitz AR, Raab-Traub N. The role of miRNAs and EBV BARTs in NPC. Semin Cancer Biol. 2012;22(2):166-172.
139. Lo KW, Chung GT, To KF. Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol. 2012;22(2):79-86.
140. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1765-1777.
141. Maxwell JH, Kumar B, Feng FY, et al. HPV-positive/p16-positive/EBVnegative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010;32(5):562-567.
142. Yeung WM, Zong YS, Chiu CT, et al. Epstein-Barr virus carriage by nasopharyngeal carcinoma in situ. Int J Cancer. 1993;53(5):746-750.
143. Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N Engl J Med. 1995;333(11):693-698.
144. Leung SF, Chan AT, Zee B, et al. Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type. Cancer. 2003;98(2):288-291.
145. Leung SF, Zee B, Ma BB, et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol. 2006;24(34):5414-5418.
146. Chan AT, Lo YM, Zee B, et al. Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst. 2002;94(21):1614-1619.
147. Lin JC, Wang WY, Chen KY, et al. Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med. 2004;350(24):2461-2470.
148. Adham M, Greijer AE, Verkuijlen SA, et al. Epstein-Barr virus DNA load in nasopharyngeal brushings and whole blood in nasopharyngeal carcinoma patients before and after treatment. Clin Cancer Res. 2013;19(8):2175-2186.
149. Chan KC, Hung EC, Woo JK, et al. Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program. Cancer. 2013;119(10):1838-1844.
150. Ma BB, Hui EP, Chan AT. Systemic approach to improving treatment outcome in nasopharyngeal carcinoma: current and future directions. Cancer Sci. 2008;99(7):1311-1318.
151. Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005;23(15):3568-3576.
152. Lee NY, Zhang Q, Pfister DG, et al. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2012;13(2):172-180.
153. Straathof KC, Bollard CM, Popat U, et al. Treatment of nasopharyngeal carcinoma with Epstein-Barr virus-specific T lymphocytes. Blood. 2005;105(5):1898-1904.
154. Wong CH, Loong HH, Hui CW, et al. Preclinical evaluation of the PI3KmTOR dual inhibitor PF-04691502 as a novel therapeutic drug in nasopharyngeal carcinoma. Invest New Drugs. 2013;31(6):1399-1408.
155. Comoli P, Pedrazzoli P, Maccario R, et al. Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes. J Clin Oncol. 2005;23(35):8942-8949.
156. Hui EP, Taylor GS, Jia H, et al. Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Res. 2013;73(6):1676-1688.
157. Wildeman MA, Novalic Z, Verkuijlen SA, et al. Cytolytic virus activation therapy for Epstein-Barr virus-driven tumors. Clin Cancer Res. 2012;18(18):5061-5070.
158. Shibata D, Weiss LM. Epstein-Barr virus-associated gastric adenocarcinoma. Am J Pathol. 1992;140(4):769-774.
159. Shin WS, Kang MW, Kang JH, et al. Epstein-Barr virus-associated gastric adenocarcinomas among Koreans. Am J Clin Pathol. 1996;105(2):174-181.
160. Chang MS, Uozaki H, Chong JM, et al. CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin Cancer Res. 2006;12(10):2995-3002.
161. Hino R, Uozaki H, Murakami N, et al. Activation of DNA methyltransferase by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res. 2009;69(7):2766-2774.
162. Fukayama M. Epstein-Barr virus and gastric carcinoma. Pathol Int. 2010;60(5):337-350.
163. Lee JH, Kim SH, Han SH, An JS, Lee ES, Kim YS. Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis. J Gastroenterol Hepatol. 2009;24(3):354-365.