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Plasma Epstein‐Barr virus (EBV) DNA measurement has established prognostic utility in EBV‐driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub‐Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B‐cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV‐positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P =.048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV‐positive patients. Unexpectedly, most HIV‐positive patients with high plasma EBV DNA at diagnosis had EBV‐negative lymphomas, as confirmed by multiple methods. Even in these HIV‐positive patients with EBV‐negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P =.014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV‐positive patients with convincingly EBV‐negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Clinical reports of multicentric Castleman disease (MCD) from sub-Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma-associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV-associated MCD patients in Malawi. To our knowledge, this is the first HIV-associated MCD case series from the region. Methods: We describe HIV-positive patients with MCD in Lilongwe, and compare them to HIV-associated lymph node Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi's 16 million people. We included adult patients≥18 years of age with HIV-associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015. Results and discussion: MCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA <400 copies/mL. Most KS and NHL patients were also on ART, although ART duration was longer for MCD (56.4 months, range 18.2–105.3) than KS (14.2 months, range 6.8–21.9, p=0.039) or NHL (13.8 months, range 0.2–98.8, p=0.017). Survival was poorer for MCD patients than lymph node KS or NHL. Conclusions: HIV-associated MCD occurs in Malawi, is diagnosed late and is associated with high mortality. Improvements in awareness, diagnostic facilities, treatment and supportive care are needed to address this likely under-recognized public health problem in SSA. [ABSTRACT FROM AUTHOR]