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

Geoffrey Buckle, Louise Maranda, Jodi Skiles, John Michael Ong'echa, Joslyn Foley, Mara Epstein, Terry Vik, Andrew Schroeder, Jennifer Lemberger, Alan Rosmarin, Scot C. Remick, Jeffrey A. Bailey, John Vulule, Juliana A. Otieno, Ann M. Moormann

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 (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.

Original languageEnglish (US)
Pages (from-to)1231-1240
Number of pages10
JournalInternational Journal of Cancer
Volume139
Issue number6
DOIs
StatePublished - Sep 15 2016

Fingerprint

Burkitt Lymphoma
Cohort Studies
Survival
Human Herpesvirus 4
Doxorubicin
Cyclophosphamide
Hemoglobins
Benchmarking
Induction Chemotherapy
Kenya
Lost to Follow-Up
Vincristine
Plasmodium falciparum
Nutritional Status
L-Lactate Dehydrogenase
Methotrexate
Malaria
Disease-Free Survival
Anemia
Neoplasms

Keywords

  • Africa
  • biomarkers
  • EBV
  • malaria
  • pediatric cancer

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011 : A historical cohort study. / Buckle, Geoffrey; Maranda, Louise; Skiles, Jodi; Ong'echa, John Michael; Foley, Joslyn; Epstein, Mara; Vik, Terry; Schroeder, Andrew; Lemberger, Jennifer; Rosmarin, Alan; Remick, Scot C.; Bailey, Jeffrey A.; Vulule, John; Otieno, Juliana A.; Moormann, Ann M.

In: International Journal of Cancer, Vol. 139, No. 6, 15.09.2016, p. 1231-1240.

Research output: Contribution to journalArticle

Buckle, G, Maranda, L, Skiles, J, Ong'echa, JM, Foley, J, Epstein, M, Vik, T, Schroeder, A, Lemberger, J, Rosmarin, A, Remick, SC, Bailey, JA, Vulule, J, Otieno, JA & Moormann, AM 2016, 'Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study', International Journal of Cancer, vol. 139, no. 6, pp. 1231-1240. https://doi.org/10.1002/ijc.30170
Buckle, Geoffrey ; Maranda, Louise ; Skiles, Jodi ; Ong'echa, John Michael ; Foley, Joslyn ; Epstein, Mara ; Vik, Terry ; Schroeder, Andrew ; Lemberger, Jennifer ; Rosmarin, Alan ; Remick, Scot C. ; Bailey, Jeffrey A. ; Vulule, John ; Otieno, Juliana A. ; Moormann, Ann M. / Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011 : A historical cohort study. In: International Journal of Cancer. 2016 ; Vol. 139, No. 6. pp. 1231-1240.
@article{ccf42f379d6a4ab7a3fcbe1b0ae9b522,
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 (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.",
keywords = "Africa, biomarkers, EBV, malaria, pediatric cancer",
author = "Geoffrey Buckle and Louise Maranda and Jodi Skiles and Ong'echa, {John Michael} and Joslyn Foley and Mara Epstein and Terry Vik and Andrew Schroeder and Jennifer Lemberger and Alan Rosmarin and Remick, {Scot C.} and Bailey, {Jeffrey A.} and John Vulule and Otieno, {Juliana A.} and Moormann, {Ann M.}",
year = "2016",
month = "9",
day = "15",
doi = "10.1002/ijc.30170",
language = "English (US)",
volume = "139",
pages = "1231--1240",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011

T2 - A historical cohort study

AU - Buckle, Geoffrey

AU - Maranda, Louise

AU - Skiles, Jodi

AU - Ong'echa, John Michael

AU - Foley, Joslyn

AU - Epstein, Mara

AU - Vik, Terry

AU - Schroeder, Andrew

AU - Lemberger, Jennifer

AU - Rosmarin, Alan

AU - Remick, Scot C.

AU - Bailey, Jeffrey A.

AU - Vulule, John

AU - Otieno, Juliana A.

AU - Moormann, Ann M.

PY - 2016/9/15

Y1 - 2016/9/15

N2 - 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 (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.

AB - 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 (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.

KW - Africa

KW - biomarkers

KW - EBV

KW - malaria

KW - pediatric cancer

UR - http://www.scopus.com/inward/record.url?scp=84977514983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977514983&partnerID=8YFLogxK

U2 - 10.1002/ijc.30170

DO - 10.1002/ijc.30170

M3 - Article

C2 - 27136063

AN - SCOPUS:84977514983

VL - 139

SP - 1231

EP - 1240

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 6

ER -