title: Plasma Epstein-Barr virus DNA for pediatric Burkitt lymphoma diagnosis, prognosis and response assessment in Malawi.
abstract: Point-of-care tools are needed in sub-Saharan Africa (SSA) to improve pediatric Burkitt lymphoma (BL) diagnosis and treatment. We evaluated plasma Epstein-Barr virus (pEBV) DNA as a pediatric BL biomarker in Malawi. Prospectively enrolled children with BL were compared to classical Hodgkin lymphoma (cHL) and nonlymphoma diagnoses. Pediatric BL patients received standardized chemotherapy and supportive care. pEBV DNA was measured at baseline, mid-treatment, and treatment completion. Of 121 assessed children, pEBV DNA was detected in 76/88 (86%) with BL, 16/17 (94%) with cHL, and 2/16 (12%) with nonlymphoma, with proportions higher in BL versus nonlymphoma (p < 0.001) and similar in BL versus cHL (p = 0.69). If detected, median pEBV DNA was 6.1 log10copies/mL for BL, 4.8 log10copies/mL for cHL, and 3.4 log10copies/mL for nonlymphoma, with higher levels in BL versus cHL (p = 0.029), and a trend toward higher levels in BL versus nonlymphoma (p = 0.062). pEBV DNA declined during treatment in the cohort overall and increased in several children before clinical relapse. Twelve-month overall survival was 40% in the cohort overall, and for children with baseline pEBV detected, survival was worse if baseline pEBV DNA was ≥6 log10copies/mL versus <6 log10copies/mL (p = 0.0002), and also if pEBV DNA was persistently detectable at mid-treatment versus undetectable (p = 0.041). Among children with baseline pEBV DNA detected, viremia was the only significant risk factor for death by 12 months in multivariate analyses (adjusted hazard ratio 1.35 per log10copies/mL, 95% CI 1.04-1.75, p = 0.023). Quantitative pEBV DNA has potential utility for diagnosis, prognosis, and response assessment for pediatric BL in SSA.
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Westmoreland
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Montgomery
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Stanley
authors.affiliation: Department of Pediatrics, Texas Children's Hospital, Houston, TX.
authors.forename: Nader Kim
authors.initials: NK
authors.lastname: El-Mallawany
authors.affiliation: Department of Pediatrics, Texas Children's Hospital, Houston, TX.
authors.forename: Peter
authors.initials: P
authors.lastname: Wasswa
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: Toon
authors.initials: T
authors.lastname: van der Gronde
authors.affiliation: Baylor College of Medicine Children's Foundation Malawi, Lilongwe, Malawi.
authors.forename: Idah
authors.initials: I
authors.lastname: Mtete
authors.affiliation: Baylor College of Medicine Children's Foundation Malawi, Lilongwe, Malawi.
authors.forename: Mercy
authors.initials: M
authors.lastname: Butia
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: Salama
authors.initials: S
authors.lastname: Itimu
authors.affiliation: Baylor College of Medicine Children's Foundation Malawi, Lilongwe, Malawi.
authors.forename: Mary
authors.initials: M
authors.lastname: Chasela
authors.affiliation: Baylor College of Medicine Children's Foundation Malawi, Lilongwe, Malawi.
authors.forename: Mary
authors.initials: M
authors.lastname: Mtunda
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: Coxcilly
authors.initials: C
authors.lastname: Kampani
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: N George
authors.initials: NG
authors.lastname: Liomba
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.|Department of Medicine, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Tamiwe
authors.initials: T
authors.lastname: Tomoka
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: Bal M
authors.initials: BM
authors.lastname: Dhungel
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: Marcia K
authors.initials: MK
authors.lastname: Sanders
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.
authors.forename: Robert
authors.initials: R
authors.lastname: Krysiak
authors.affiliation: Baylor College of Medicine Children's Foundation Malawi, Lilongwe, Malawi.
authors.forename: Peter
authors.initials: P
authors.lastname: Kazembe
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fedoriw
authors.affiliation: Cancer Program, UNC Project-Malawi, Lilongwe, Malawi.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.|Department of Medicine, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Satish
authors.identifier: 0000-0003-2314-0316
authors.initials: S
authors.lastname: Gopal
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002051:Burkitt Lymphoma / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*; D002648:Child; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006689:Hodgkin Disease / Q000473:pathology / Q000821:virology; D006801:Humans; D008295:Malawi; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology / Q000821:virology; D010949:Plasma / Q000821:virology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019562:Viral Load / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral
keywords: Burkitt lymphoma; Epstein-Barr virus; Hodgkin lymphoma; sub-Saharan Africa