Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study

• Published in: International journal of cancer 2016-09, Vol.139 (6), p.1231-1240
• Main Authors: Buckle, Geoffrey, Maranda, Louise, Skiles, Jodi, Ong'echa, John Michael, Foley, Joslyn, Epstein, Mara, Vik, Terry A., Schroeder, Andrew, Lemberger, Jennifer, Rosmarin, Alan, Remick, Scot C., Bailey, Jeffrey A., Vulule, John, Otieno, Juliana A., Moormann, Ann M.
• Format: Article
• Language: English
• Subjects: Adolescent; Africa; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; biomarkers; Biopsy; Burkitt Lymphoma - diagnosis; Burkitt Lymphoma - epidemiology; Burkitt Lymphoma - history; Burkitt Lymphoma - mortality; Cancer; Chemotherapy; Child; Child, Preschool; Cohort Studies; EBV; Epstein-Barr virus; Female; Health risk assessment; History, 21st Century; Hospital Mortality; Humans; Infant; Kaplan-Meier Estimate; Kenya - epidemiology; Lymphoma; malaria; Male; Medical research; Mortality; Neoplasm Staging; pediatric cancer; Pediatrics; Plasmodium falciparum; Population Surveillance; Risk Factors; Survival Rate
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30170

Discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource‐constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein‐Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this 10 year prospective study period, 22% died in‐hospital and 78% completed six‐courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event‐free‐survival; and 31% were lost to follow‐up; the overall one‐year survival was 45%. After adjusting for covariates, low hemoglobin (400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR) = 1.57 [0.97–2.41]) and aHR = 1.84, [0.91–3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10–11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System‐level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (aHR = 1.43 [0.84–2.43]) or doxorubicin (aHR = 1.25, [0.66–2.35]), compared with those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches. What's new? Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer diagnosed in Equatorial Africa. However, while B‐cell lymphomas have the potential for complete remission, estimated survival rates for eBL patients in Africa are low, likely owing to unique regional factors. The present study shows that malaria, anemia and high‐dose cyclophosphamide contribute to poor outcomes for African children diagnosed with eBL. Importantly, peripheral blood titers of Epstein‐Barr virus, an eBL risk factor, were not associated with patient outcome. The findings provide a basis for the future evaluation of strategies to improve eBL treatment and survival.