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Socioeconomic position and maintenance therapy in children with acute lymphoblastic leukemia: A national cohort study
Line Hjøllund Pedersen1,2, Anna Østergaard1,3,4, Victoria Bank1
1Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
Insights
Physician compliance, not family adherence, may explain socioeconomic disparities in childhood acute lymphoblastic leukemia (ALL) survival. Lower prescribed drug doses in lower socioeconomic groups suggest a need to improve physician adherence to ALL treatment protocols.
Area of Science:
- Pediatric Hematology Oncology
- Clinical Pharmacology
- Public Health
Background:
- Socioeconomic disparities in childhood acute lymphoblastic leukemia (ALL) survival are documented in high-income nations.
- Identifying vulnerable patient subgroups is crucial for targeted interventions.
- Differences in survival may emerge during maintenance therapy, potentially due to physician or family adherence issues.
Purpose of the Study:
- To investigate the association between socioeconomic position and adherence to maintenance therapy in childhood ALL.
- To determine whether physician compliance or family adherence contributes to socioeconomic disparities in ALL treatment.
Main Methods:
- Nationwide cohort study of 173 Danish children treated with ALL2008 protocol (2008-2016).
- Extensive monitoring of methotrexate (MTX)/6-mercaptopurine (6MP) dosing and metabolite levels.
- Retrospective analysis of adherence based on parental education, employment, and income.
Main Results:
- Lower prescribed doses of MTX and 6MP were observed in children from families with lower parental education and unemployment.
- Analysis of MTX and 6MP metabolite levels revealed no significant differences in family adherence based on socioeconomic factors.
- This suggests socioeconomic disparities are not driven by patient non-adherence to medication.
Conclusions:
- Inferior physician compliance to protocol recommendations on drug dosage may contribute to socioeconomic disparities in childhood ALL cure rates.
- Family adherence to maintenance therapy does not appear to be the primary driver of these disparities.
- Further research is needed to explore the precise mechanisms underlying physician non-compliance.
Background:
Socioeconomic differences in survival among children with acute lymphoblastic leukemia (ALL) have been reported in high-income countries and there is an unmet need for strategies to identify vulnerable patient subgroups. Reported differences in survival for children from families with different socioeconomic positions seem to arise when starting maintenance therapy. This could reflect reduced physician's compliance or family adherence to maintenance therapy.
Methods:
This nationwide cohort study with extensive monitoring of systemic methotrexate (MTX)/6-mercaptopurine (6MP) dosing and metabolite levels, retrospectively investigated 173 Danish children treated according to The Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol from 2008 to 2016.
Results:
Significantly lower prescribed doses of MTX and 6MP were seen in the children in families with short parental education (short vs. medium vs. higher education: mMTX: 13.8, 16.2, and 18.6 mg/m2 /week; p < .01; m6MP: 47.4, 64.9, and 66.1 mg/m2 /day; p = .03) or parents unemployed/not in workforce (unemployed/not in workforce vs. mixed vs. at work: mMTX: 15.0, 19.9, and 17.2 mg/m2 /week; p < .01; m6MP: 54.8, 72.0, and 65.1 mg/m2 /day; p < .01). When assessing family adherence by analyzing MTX and 6MP metabolite levels, including per prescribed dose of MTX and 6MP, we found no significant differences by levels of parental education, affiliation to work market, or income (p > .05 for all comparisons).
Conclusions:
These results indicate that inferior physician compliance to protocol recommendations on drug dosage rather than families' adherence to therapy may contribute to the association between socioeconomic position and cure rates in childhood ALL, although precise mechanisms remain to be explored.
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