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Physician compliance and relapse rates of acute lymphoblastic leukemia in children
M Peeters1, G Koren, D Jakubovicz
1Division of Hematology-Oncology, Hospital for Sick Children, Toronto, Ontario.
Abstract:
We studied the prescription patterns of maintenance therapy for children with acute lymphoblastic leukemia and their association with duration of complete remission. Both 6-mercaptopurine and methotrexate (MTX) were prescribed in doses significantly lower than those recommended (75 mg/m2 daily 6-mercaptopurine; 20 mg/m2 weekly MTX) during maintenance therapy. Of 212 evaluated patients, patients who had relapses (n = 101) received significantly less MTX compared with patients who did not have relapses (n = 111) during the first 2 years of maintenance therapy. In the group of standard-risk patients who received the same induction therapy (n = 92), 11 of 17 who received less than 50% of the recommended MTX dose (64%) and 28 of 75 who received greater than 50% of the dose (37%) had relapses (P less than 0.05). The two groups had comparable periods of interruption of MTX therapy. Further analysis revealed that the lower maintenance dose stemmed from a continuous low prescribed dose and not from more frequent interruption of therapy in relapse. Physicians' inability or failure to adhere to the recommended protocol was associated with a higher relapse rate of acute lymphoblastic leukemia. Improved physicians' compliance may improve the prognosis of the disease.
Insights
Physicians often prescribed lower doses of 6-mercaptopurine and methotrexate (MTX) for childhood acute lymphoblastic leukemia maintenance therapy. Lower MTX doses correlated with higher relapse rates, suggesting improved physician adherence could enhance patient outcomes.
Area of Science:
- Pediatric Oncology
- Hematology
- Pharmacology
Background:
- Maintenance therapy is crucial for treating childhood acute lymphoblastic leukemia (ALL).
- Standard maintenance protocols involve 6-mercaptopurine and methotrexate (MTX).
- Suboptimal dosing may impact remission duration and relapse rates.
Purpose of the Study:
- To investigate ALL maintenance therapy prescription patterns.
- To assess the association between prescribed drug doses and remission duration.
- To identify factors contributing to suboptimal dosing.
Main Methods:
- Retrospective analysis of 212 pediatric ALL patients.
- Evaluation of 6-mercaptopurine and methotrexate (MTX) prescription doses.
- Comparison of MTX doses between relapsed and non-relapsed patients.
- Analysis of dose adherence and therapy interruptions.
Main Results:
- Patients received significantly lower doses of 6-mercaptopurine and MTX than recommended.
- Lower MTX doses in the first two years of maintenance were associated with higher relapse rates.
- Suboptimal dosing resulted from consistently low prescribed amounts, not increased interruptions.
- Physician non-adherence to protocols was linked to increased ALL relapse rates.
Conclusions:
- Physician adherence to recommended MTX and 6-mercaptopurine doses is critical for effective ALL maintenance therapy.
- Improving physician compliance with established protocols may lead to better remission durations and improved patient prognosis.
- Suboptimal dosing is a significant factor in ALL relapses.