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Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia
- Source :
- The New England journal of medicine. 338(8)
- Publication Year :
- 1998
-
Abstract
- The rate of clearance of antileukemic agents differs by a factor of 3 to 10 among children with acute lymphoblastic leukemia. We hypothesized that the outcome of treatment would be improved if doses were individualized to prevent low systemic exposure to the drugs in patients with fast drug clearance.We stratified and randomly assigned 182 children with newly diagnosed acute lymphoblastic leukemia to postremission regimens that included high-dose methotrexate and teniposide plus cytarabine. The doses of these drugs were based on body-surface area (in the conventional-therapy group) or the rates of clearance of the three medications in each patient (in the individualized-treatment group). In the individualized-treatment group, doses were increased in patients with rapid clearance and decreased in patients with very slow clearance.Patients who received individualized doses had significantly fewer courses of treatment with systemic exposures below the target range than did patients who received conventional doses (P0.001 for each medication). Among the patients with B-lineage leukemia, those who received individualized therapy had a significantly better outcome than those given conventional therapy (P=0.02); the mean (+/-SE) rates of continuous complete remission at five years were 76+/-6 percent and 66+/-7 percent, respectively. There was no significant difference between treatments for patients with T-lineage leukemia (P=0.54). In a proportional-hazards model, the time-dependent systemic exposure to methotrexate, but not to teniposide or cytarabine, was significantly related to the risk of early relapse in children with B-lineage leukemia.Adjusting the dose of methotrexate to account for the patient's ability to clear the drug can improve the outcome in children with B-lineage acute lymphoblastic leukemia.
- Subjects :
- Male
medicine.medical_specialty
Adolescent
medicine.drug_class
Metabolic Clearance Rate
medicine.medical_treatment
Antimetabolite
Patient Care Planning
chemistry.chemical_compound
Acute lymphocytic leukemia
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Leukemia, B-Cell
Humans
Prospective Studies
Child
Childhood Acute Lymphoblastic Leukemia
Proportional Hazards Models
Teniposide
Chemotherapy
business.industry
Remission Induction
Cytarabine
Infant
General Medicine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease
Survival Analysis
Surgery
Methotrexate
chemistry
Child, Preschool
Antifolate
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 00284793
- Volume :
- 338
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- The New England journal of medicine
- Accession number :
- edsair.doi.dedup.....91b5db04c3d6b8829cb7058d6ab1758d