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To define the clinical and biologic significance of childhood acute mixed-lineage leukemia diagnosed by stringent criteria, we studied 25 cases of acute lymphoblastic leukemia expressing greater than or equal to 2 myeloid-associated antigens (My+ ALL), and 16 cases of acute myeloid leukemia expressing greater than or equal to 2 lymphoid associated antigens(More)
CONTEXT Little is known about the incidence of secondary neoplasms after 15 to 20 years in children and adolescents who were treated for acute lymphoblastic leukemia. OBJECTIVES To investigate the cumulative incidence of secondary neoplasms in pediatric patients treated for acute lymphoblastic leukemia over 30 years and to characterize late-occurring(More)
BACKGROUND Patients with acute lymphoblastic leukemia are often treated with 6-mercaptopurine, and those with homozygous deficiency in thiopurine S-methyltransferase (TPMT) enzyme activity have an extreme sensitivity to this drug as a result of the accumulation of higher cellular concentrations of thioguanine nucleotides. We studied the metabolism, dose(More)
BACKGROUND Many antileukaemic agents or their metabolites are inactivated by liver enzymes. Most anticonvulsant drugs induce drug-metabolising enzymes and thereby increase the clearance of anticancer agents. We investigated whether anticonvulsants compromise the efficacy of cancer chemotherapy. METHODS We identified whom of 716 children treated(More)
Cancer is a significant health problem in the adolescent and young adult population. Confusion exists within the field of pediatric oncology with respect to the definition of childhood cancer, since most population-based incidence studies define childhood cancer on the basis of age alone. We recommend that the scope of pediatric oncology include the study(More)
BACKGROUND Brain tumours rarely occur in survivors of childhood acute lymphoblastic leukaemia after cranial radiotherapy. An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. METHODS We assessed(More)
BACKGROUND The clinical significance of submicroscopic levels of leukaemic cells in bone-marrow aspirates from children with acute lymphoblastic leukaemia (ALL) remains controversial. We prospectively determined the frequency and prognostic importance of minimal residual disease detected by a rapid immunological assay in bone-marrow aspirates of children(More)
Early clearance of leukemic cells is a favorable prognostic indicator in childhood acute lymphoblastic leukemia (ALL). However, identification of residual leukemic cells by their morphologic features is subjective and lacks sensitivity. To improve estimates of leukemia clearance, we applied flow cytometric techniques capable of detecting 1 leukemic cell in(More)
Event-free survival for children with acute lymphoblastic leukemia (ALL) now exceeds 80% in the most effective trials. Failures are due to relapse, toxicity, and second cancers such as therapy-related myeloid leukemia or myelodysplasia (t-ML). Topoisomerase II inhibitors and alkylators can induce t-ML; additional risk factors for t-ML remain poorly defined.(More)
Methotrexate (MTX) and mercaptopurine (MP) are widely used antileukemic agents that inhibit de novo purine synthesis (DNPS) as a mechanism of their antileukemic effects. To elucidate pharmacodynamic differences among children with acute lymphoblastic leukemia (ALL), DNPS was measured in leukemic blasts from newly diagnosed patients before and after therapy(More)