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Racial differences in the survival of childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group
B H Pollock1, M R DeBaun, B M Camitta
1University of Florida, and Pediatric Oncology Group Statistical Office, Gainesville, FL, USA. brad@pog.ufl.edu
Insights
African-American (AA) and Spanish surname (SS) children with acute lymphoblastic leukemia have lower survival rates than white children. This disparity is likely due to chemotherapy response, not compliance, suggesting a need for personalized treatment.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- Acute lymphoblastic leukemia (ALL) is a common childhood cancer.
- Survival rates for ALL have improved significantly, but disparities persist among different racial and ethnic groups.
- Understanding the factors contributing to these disparities is crucial for improving outcomes.
Purpose of the Study:
- To investigate survival differences in newly diagnosed B-precursor ALL between African-American (AA) and Spanish surname (SS) children compared to white children.
- To adjust for biologic factors and identify potential causes for observed survival disparities.
Main Methods:
- A historic cohort study involving 4,061 white, 518 AA, and 507 SS children aged 1-20 years.
- Patients were treated on three successive Pediatric Oncology Group multicenter randomized clinical trials from 1981 to 1994.
- Statistical analysis included adjustment for age, leukocyte count, sex, era of treatment, and leukemia blast cell ploidy.
Main Results:
- AA and SS patients presented with more adverse prognostic features and had lower survival rates than white patients.
- Five-year cumulative survival rates were 81.9% ± 0.6% for white, 68.6% ± 2.1% for AA, and 74.9% ± 2.0% for SS children.
- Adjusted analyses revealed a 42% excess mortality for AA children (PHR=1.42) and a 33% excess mortality for SS children (PHR=1.33) compared to white children.
Conclusions:
- Observed survival differences were not explained by clinical presentation, tumor biology, or adherence to therapy.
- Disparities in outcome are likely linked to variations in chemotherapeutic response, not compliance.
- Future improvements may necessitate individualized dosing strategies, potentially guided by pharmacogenetic profiles, particularly for AA and SS children.
Purpose:
We conducted a historic cohort study to test the hypothesis that, after adjustment for biologic factors, African-American (AA) children and Spanish surname (SS) children with newly diagnosed B-precursor acute lymphoblastic leukemia had lower survival than did comparable white children.
Patients And Methods:
From 1981 to 1994, 4,061 white, 518 AA, and 507 SS children aged 1 to 20 years were treated on three successive Pediatric Oncology Group multicenter randomized clinical trials.
Results:
AA and SS patients were more likely to have adverse prognostic features at diagnosis and lower survival than were white patients. The 5-year cumulative survival rates were (probability +/- SE) 81.9% +/- 0.6%, 68.6% +/- 2.1%, and 74.9% +/- 2.0% for white, AA, and SS children, respectively. Adjusting for age, leukocyte count, sex, era of treatment, and leukemia blast cell ploidy, we found that AA children had a 42% excess mortality rate compared with white children (proportional hazards ratio [PHR] = 1.42; 95% confidence interval [CI], 1.12 to 1. 80), and SS children had a 33% excess mortality rate compared with white children (PHR = 1.33; 95% CI, 1.19 to 1.49).
Conclusion:
Clinical presentation, tumor biology, and deviations from prescribed therapy did not explain the differences in survival and event-free survival that we observed, although differences seem to be diminishing over time with improvements in therapy. The disparity in outcome for AA and SS children is most likely related to variations in chemotherapeutic response to therapy and not to compliance. Further improvements in outcome may require individualized dosing based on specific pharmacogenetic profiles, especially for AA and SS children.