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 non-lymphoma 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 non-lymphoma, with proportions higher in BL versus non-lymphoma (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 non-lymphoma, with higher levels in BL versus cHL (p=0.029), and a trend toward higher levels in BL versus non-lymphoma (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.

High pretreatment plasma Epstein‐Barr virus (EBV) DNA level is a poor prognostic marker in HIV‐associated, EBV‐negative diffuse large B‐cell lymphoma in Malawi

“…We and others have suggested that plasma EBV measurement may be particularly informative in SSA and other low‐income settings, where EBV‐associated lymphomas are common . This hypothesis has generally been confirmed for lymphomas that are invariably EBV‐positive, like endemic Burkitt lymphoma and HIV‐associated classic Hodgkin lymphoma . In such cases, plasma EBV functions as a sensitive circulating tumor DNA (ctDNA) marker, with both prognostic and monitoring utility.…”

“…Plasma EBV measurement is a clinically valuable and highly implementable biomarker for many EBV‐associated malignancies . We and others have suggested that plasma EBV measurement may be particularly informative in SSA and other low‐income settings, where EBV‐associated lymphomas are common . This hypothesis has generally been confirmed for lymphomas that are invariably EBV‐positive, like endemic Burkitt lymphoma and HIV‐associated classic Hodgkin lymphoma .…”

Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary Lymphoepithelioma-like Carcinoma (LELC) Patients

“…[24][25][26][27] It may also have a role in monitoring response in some lymphomas. 28,29 EBV DNA has also been found in the serum of patients with EBVassociated gastric cancer. 30,31 Cell-free EBV DNA can be found in the plasma of patients with pulmonary LELC.…”

Oral shedding of herpesviruses in HIV-infected patients with varying degrees of immune status

“…CMV plasma VL is closely linked to immune suppression, whether by HIV or iatrogenic drug regimen [35, 38] . A close association between plasma VL and disease burden also holds true for EBV-associated post-transplant lymphoproliferative disease and some EBV-positive lymphoma [39, 40] , but not always for KSHV and KS [41] . A5254 found that oral shedding of HSV-1 and CMV, but not of EBV and KSHV, were correlated with immune deficiency.…”