Deoxycoformycin treatment for childhood T-cell acute lymphoblastic leukemia early in second remission: a Pediatric Oncology Group Study.

2-Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol (#8303) for children with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma in first relapse. Twenty-seven patients received one or more courses of DCF at 15 mg/m2/day as a 3-day continuous infusion immediately after achieving a second remission with a four-drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF.

Phase I and clinical pharmacological study of 4-demethoxydaunorubicin (idarubicin) in children with advanced cancer.

We conducted a phase I and pharmacokinetic study of i.v. idarubicin, a new anthracycline analogue, in 42 evaluable children 1-19 years old.

Phase I study of iproplatin in pediatric patients: a Pediatric Oncology Group Study.

Iproplatin was evaluated in a phase I study in children to determine the maximum tolerated dosage. The dose-limiting toxic effect was found to be myelosuppression, which in part was related to the amount of prior therapy with irradiation and other anticancer agents. The dosage recommended for phase II trials in children is 324 mg/m2 iv over 2 hours every 3-4 weeks.

Methotrexate (MTX) concentration in tumors following low-dose MTX.

Methotrexate (MTX) is a folate analog competitive with reduced folates for cellular transport and metabolism. Since the normal plasma folate concentration is only 10(-8) M, we tested the possibility that there may be a saturable uptake of MTX by proliferating tumor tissue at plasma MTX concentrations of only 10(-7) to 10(-6) M. Patients with advanced malignancies, refractory to accepted therapy, were given low-dose oral MTX (30-60 mg/m2 total dose in four to eight divided doses).

Folate and methotrexate polyglutamate tissue levels in rhesus monkeys following chronic low-dose methotrexate.

Methotrexate (MTX), a mainstay in the treatment of acute lymphoblastic leukemia, is associated with both hepatic and neurologic toxicity. Like a folate, MTX is metabolized to polyglutamated derivatives (MTXGlun) with long intracellular half-lives. These metabolites may contribute to MTX toxicity through a direct effect on cellular metabolism or indirectly through a perturbation of folate homeostasis.

Terminal deoxynucleotidyl transferase activity in childhood leukemia.

The activity of terminal deoxynucleotidyl transferase (Tdt) was measured in mononuclear cells of 70 children with acute leukemia, in whom raised levels of Tdt were noted at diagnosis, relapse, or during remission. Serial measurements of Tdt activity were related to the percentage of blasts in the bone marrow and the clinical course of children both during therapy and after its completion. The Tdt values did not predict relapse in children with acute lymphoblastic leukemia nor did the quantitative determination correlate with the percentage of blasts in the bone marrow.