Plasma Epstein-Barr virus DNA for pediatric Burkitt lymphoma diagnosis, prognosis, and response assessment in Malawi

Details

• Alternative Title:
  Int J Cancer
• Personal Author:
  Westmoreland, Katherine D. ; Montgomery, Nathan D. ; Stanley, Christopher C. ; El-Mallawany, Nader Kim ; Wasswa, Peter ; van der Gronde, Toon ; Mtete, Idah ; Butia, Mercy ; Itimu, Salama ; Chasela, Mary ; Mtunda, Mary ; Kampani, Coxcilly ; Liomba, N. George ; Tomoka, Tamiwe ; Dhungel, Bal M. ; Sanders, Marcia K. ; Krysiak, Robert ; Kazembe, Peter ; Dittmer, Dirk P. ; Fedoriw, Yuri ; Gopal, Satish
• Description:
  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 log| copies/mL for BL, 4.8 log| copies/mL for cHL, and 3.4 log| copies/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 log| copies/mL versus <6 log| copies/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 log| copies/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.
• Subjects:
  Biomarkers, Tumor Burkitt Lymphoma Child DNA, Viral Epstein-Barr Virus Infections Female Herpesvirus 4, Human Hodgkin Disease Humans Malawi Male Neoplasm Recurrence, Local Plasma Prognosis Proportional Hazards Models Prospective Studies Viral Load

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• Keywords:
  Burkitt Lymphoma Epstein-Barr Virus Hodgkin Lymphoma Sub-Saharan Africa
• Source:
  Int J Cancer. 140(11):2509-2516
• Pubmed ID:
  28268254
• Pubmed Central ID:
  PMC5386821
• Document Type:
  Journal Article
• Funding:
  P01 CA019014/CA/NCI NIH HHSUnited States/ ; K01 TW009488/TW/FIC NIH HHSUnited States/ ; P30 CA016086/CA/NCI NIH HHSUnited States/ ; U2G PS001965/PS/NCHHSTP CDC HHSUnited States/ ; U54 CA190152/CA/NCI NIH HHSUnited States/ ; R25 TW009340/TW/FIC NIH HHSUnited States/ ; P30 AI050410/AI/NIAID NIH HHSUnited States/ ; R21 CA180815/CA/NCI NIH HHSUnited States/
• Volume:
  140
• Issue:
  11
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f63bc6afaf3894f04dd0bb5ec300bb7deff81d1f9e745d6a05d2b6d52a175a9d
• Download URL:
  https://stacks.cdc.gov/view/cdc/45108/cdc_45108_DS1.pdf
• File Type:
  [PDF - 492.94 KB ]