title: Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study.
abstract: 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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Buckle
authors.affiliation: Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Louise
authors.initials: L
authors.lastname: Maranda
authors.affiliation: Department of Pediatrics, Hemotology/Oncology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Jodi
authors.initials: J
authors.lastname: Skiles
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: John Michael
authors.initials: JM
authors.lastname: Ong'echa
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Joslyn
authors.initials: J
authors.lastname: Foley
authors.affiliation: Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Mara
authors.initials: M
authors.lastname: Epstein
authors.affiliation: Department of Hemotology/Oncology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Vik
authors.affiliation: Research and Analysis Department, Direct Relief, Goleta, CA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Schroeder
authors.affiliation: Research and Analysis Department, Direct Relief, Goleta, CA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lemberger
authors.affiliation: Department of Hematology/Oncology, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Alan
authors.initials: A
authors.lastname: Rosmarin
authors.affiliation: Department of Oncology and Senior Scientist, Maine Medical Center and Maine Medical Center Research Institute, Portland, ME.
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bailey
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: John
authors.initials: J
authors.lastname: Vulule
authors.affiliation: Jaramogi Oginga Odinga Teaching and Referral Hospital, Kenya Ministry of Health, Kisumu, Kenya.
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Otieno
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Moormann
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000453:epidemiology* / Q000266:history / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D049674:History, 21st Century; D017052:Hospital Mortality; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007630:Kenya / Q000453:epidemiology; D008297:Male; D009367:Neoplasm Staging; D011159:Population Surveillance; D012307:Risk Factors; D015996:Survival Rate
keywords: Africa; EBV; biomarkers; malaria; pediatric cancer