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 ten 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 co-variates, low hemoglobin (<8g/dL) and high LDH (>400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR)=1.57 [0.97 to 2.41]) and aHR=1.84, [0.91 to 3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10 to 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 to 2.43]), or doxorubicin (aHR=1.25, [0.66 to 2.35]), compared to 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.

Regulatory T Cells in Endemic Burkitt Lymphoma Patients Are Associated with Poor Outcomes: A Prospective, Longitudinal Study

“…Non-survivors included in this study tended to be younger (median age 5.3 years, range 2.3–9.0) than survivors (median age 9.0 years, range 3.8–13.4), relapse patients (median age 6.7, range 5.8–10.4), and healthy controls (median age 6.5 years, range 2.7–13.0 years). In analysis of covariance, age did not exert a significant effect, and in the overall study population age is not a predictor of survival [19]. Complete blood count was used to convert cell frequencies into absolute counts; N = 14 non-survivors, 11 survivors, 11 healthy controls.…”

“…The demographic characteristics and chemotherapeutic treatment regimen of our eBL study population from western Kenya has been described in more detail elsewhere [19]. For this sub-study, we included 38 eBL patients between the ages of 2–13 years old (median age 6.7 years), who were prospectively enrolled between August 2008 and January 2010 upon admittance to Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) in Kisumu, Kenya.…”

Poorly cytotoxic terminally differentiated CD56negCD16pos NK cells accumulate in Kenyan children with Burkitt lymphomas

“…39 Two independent pathologists in Kenya confirmed the diagnosis by cytopathology and May-Grünwald Giemsa staining. In this region, eBL is the most common pediatric cancer; 95% of children clinically suspected of having the disease are pathologically confirmed with eBL.…”

“…The survival rate for eBL children included in this study was 57%, similar to our larger study cohort. 39 Our eBL group was divided into 2 subgroups based on EBV status: no/low EBV loads detected in peripheral blood by quantitative polymerase chain reaction and high EBV copy numbers (.3 log EBV copies per microgram of DNA). This threshold was determined previously in comparisons of healthy Kisumu and eBL children.…”

Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type–Specific Differences

“…Endemic BL shows distinctive presentation in either the jaw or the abdomen (17); among Kenyan children within our larger BL cohort, the tumor presentation sites were 43% jaw and 50% abdomen (18). In addition, during the study period between 2003 and 2011, 22% of the admitted patients died in-hospital and 78% completed the course of chemotherapy treatment (18). In this respect, there was a dramatic difference between the survival rates with 63% of patients with jaw tumors surviving compared to 33% for abdominal tumors.…”