Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study
Program in Molecular Medicine; Department of Quantitative Health Sciences; Department of Medicine, Division of Hematology/Oncology; Department of Medicine, Division of Transfusion Medicine
Clinical Epidemiology | Epidemiology | Hemic and Lymphatic Diseases | Immune System Diseases | Infectious Disease | International Public Health | Neoplasms | Pediatrics
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 ( < 8 g/dL) and high LDH ( > 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 (a HR = 1.43 [0.84-2.43]) or doxorubicin (a HR = 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.
Africa, EBV, biomarkers, malaria, pediatric cancer
DOI of Published Version
Int J Cancer. 2016 Sep 15;139(6):1231-40. doi: 10.1002/ijc.30170. Epub 2016 May 18. Link to article on publisher's site
International journal of cancer
Buckle, Geoffrey C.; Maranda, Louise; Skiles, Jodi; Ong'echa, John Michael; Foley, Joslyn; Epstein, Mara M.; Vik, Terry A.; Schroeder, Andrew; Lemberger, Jennifer; Rosmarin, Alan G.; Remick, Scot C.; Bailey, Jeffrey A.; Vulule, John; Otieno, Juliana A.; and Moormann, Ann M., "Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study" (2016). University of Massachusetts Medical School Faculty Publications. 1016.