Burkitt lymphoma (BL) is the most common paediatric cancer in sub-Saharan Africa (SSA). Anthracyline-based treatment is standard in resource-rich settings, but has not been described in SSA. Children ≤ 18 years of age with newly diagnosed BL were prospectively enrolled from June 2013 to May 2015 in Malawi. Staging and supportive care were standardized, as was treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for six cycles. Among 73 children with BL, median age was 9.2 years (interquartile range 7.7–11.8), 48 (66%) were male and two were positive for human immunodeficiency virus. Twelve (16%) had stage I/II disease, 36 (49%) stage III and 25 (34%) stage IV. Grade 3/4 neutropenia occurred in 17 (25%), and grade 3/4 anaemia in 29 (42%) of 69 evaluable children. Eighteen-month overall survival was 29% (95% confidence interval [CI] 18–41%) overall. Mortality was associated with age >9 years [hazard ratio [HR] 2.13, 95% CI 1.15–3.94], female gender (HR 2.12, 95% CI 1.12–4.03), stage (HR 1.52 per unit, 95% CI 1.07–2.17), lactate dehydrogenase (HR 1.03 per 100 iu/l, 95% CI 1.01–1.05), albumin (HR 0. 96 per g/l, 95% CI 0.93–0.99) and performance status (HR 0.78 per 10-point increase, 95% CI 0.69–0.89). CHOP did not improve outcomes in paediatric BL compared to less intensive regimens in Malawi.
These findings highlight families at risk for treatment abandonment, underlying reasons, and opportunities to improve retention in care for pediatric cancer patients in SSA.
Background
Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein–Barr virus (EBV) are prevalent.
Methods
We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment and evaluation, including HIV status and EBV testing of tumors and plasma.
Results
Among 31 patients with confirmed cHL, the median age was 19 years (range, 2–51 years) and 22 (71%) were male. Sixteen patients (52%) had stage III/IV, 25 (81%) B symptoms, and 16 (52%) performance status impairment. Twenty-three patients (74%) had symptoms >6 months, and 11 of 29 (38%) had received empiric antituberculosis treatment. Anemia was common with median hemoglobin 8.2 g/dL (range, 3.1–17.1 g/dL), which improved during treatment. No children and 5 of 15 adults (33%)were HIV+. All HIV+ patients were on antiretroviral therapy for a median 15 months (range, 2–137 months), with median CD4 count 138 cells/μL (range, 23–329 cells/μL) and four (80%) having undetectable HIV. EBV was present in 18 of 24 (75%) tumor specimens, including 14 of 20 (70%) HIV− and 4 of 4 (100%) HIV+. Baseline plasma EBV DNA was detected in 25 of 28 (89%) patients, with median viral load 4.7 (range, 2.0–6.7) log10copies/mL, and subsequently declined in most patients. At 12 months, overall survival was 75% (95% confidence interval [CI], 55%–88%) and progression-free survival 65% (95% CI, 42%–81%). Baseline plasma EBV DNA and persistent viremia during treatment were associated with poorer outcomes.
Conclusion
cHL in Malawi is characterized by delayed diagnosis and advanced disease. Most cases were EBV associated and one-third of adults were HIV+. Despite resource limitations, 12-month outcomes were good.
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.
Translation and cultural validation of the PROMIS-25 into Chichewa for Malawi was successful. Baseline HRQoL for patients with pediatric lymphoma in Malawi is poor for all domains except peer relationships. This emphasizes an urgent need to address HRQoL among children undergoing cancer treatment in SSA using self-reported instruments validated within the local context.
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