title: Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial.
abstract: Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cutoff of >60 viral copies/100 µL plasma yielded 96% concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(+) by this cutoff. Patients with pretreatment EBV(+) plasma (n = 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n = 274), log-rank P = .009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(+) patients (n = 7) had inferior FFS compared with plasma EBV(-) patients (n = 125), log-rank P = .007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003389.
authors: Johns Hopkins University, School of Medicine, Baltimore, MD 21287, USA.
authors: Jennifer A
authors: JA
authors: Kanakry
authors: Hailun
authors: H
authors: Li
authors: Lan L
authors: LL
authors: Gellert
authors: M Victor
authors: MV
authors: Lemas
authors: Wen-son
authors: WS
authors: Hsieh
authors: Fangxin
authors: F
authors: Hong
authors: King L
authors: KL
authors: Tan
authors: Randy D
authors: RD
authors: Gascoyne
authors: Leo I
authors: LI
authors: Gordon
authors: Richard I
authors: RI
authors: Fisher
authors: Nancy L
authors: NL
authors: Bartlett
authors: Patrick
authors: P
authors: Stiff
authors: Bruce D
authors: BD
authors: Cheson
authors: Ranjana
authors: R
authors: Advani
authors: Thomas P
authors: TP
authors: Miller
authors: Brad S
authors: BS
authors: Kahl
authors: Sandra J
authors: SJ
authors: Horning
authors: Richard F
authors: RF
authors: Ambinder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood*; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006689:Hodgkin Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008466:Mechlorethamine / Q000627:therapeutic use; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009656:North America; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012680:Sensitivity and Specificity; D014747:Vinblastine / Q000008:administration & dosage / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D001761:Bleomycin; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D011241:Prednisone
references: Int J Cancer. 1990 Nov 15;46(5):801-4
references: 2172169
references: Clin Cancer Res. 2006 Jan 15;12(2):460-4
references: 16428487
references: J Clin Oncol. 2013 Feb 20;31(6):684-91
references: 23182987
references: Blood. 1993 Jan 15;81(2):462-7
references: 8380725
references: Blood. 2004 Jul 1;104(1):243-9
references: 15031209
references: Cancer Res. 1999 Nov 1;59(21):5452-5
references: 10554016
references: Leuk Lymphoma. 2013 Jan;54(1):41-5
references: 22667341
references: Clin Cancer Res. 2011 May 1;17(9):2885-92
references: 21478335
references: Int J Cancer. 1999 Aug 20;84(4):442-8
references: 10404101
references: Cancer Res. 2003 May 1;63(9):2028-32
references: 12727814
references: Sao Paulo Med J. 2006 May 4;124(3):154-7
references: 17119693
references: Blood. 2012 Oct 18;120(16):3280-7
references: 22948049
references: Diagn Mol Pathol. 2004 Jun;13(2):61-8
references: 15167006
references: Blood. 2012 May 3;119(18):4129-32
references: 22343727
references: APMIS. 2011 Jan;119(1):10-6
references: 21143522
references: Leuk Lymphoma. 2004 Mar;45(3):489-97
references: 15160910
references: J Clin Oncol. 2006 Dec 1;24(34):5414-8
references: 17135642
references: Int J Cancer. 1997 Feb 7;70(4):375-82
references: 9033642
references: Eur J Cancer. 2001 Oct;37(15):1853-7
references: 11576839
references: Blood. 2005 Oct 1;106(7):2444-51
references: 15941916
references: Clin Cancer Res. 2012 Jul 15;18(14):3762-71
references: 22645050
references: J Mol Diagn. 2004 Nov;6(4):378-85
references: 15507678
references: Ann N Y Acad Sci. 2000 Apr;906:99-101
references: 10818603
references: Cancer Res. 2000 Dec 15;60(24):6878-81
references: 11156384
references: Blood. 2012 Sep 6;120(10):2003-10
references: 22826562