Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: enzymological and clinical aspects.

Background: Inosine 5'-monophosphate dehydrogenase (IMPDH; EC1.1.1.

Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2.

The bacterial enzyme carboxypeptidase G2 (CPDG2) rapidly hydrolyzes methotrexate to inactive metabolites. We administered recombinant CPDG2 (2000 U) intrathecally to seven cancer patients 3 to 9 hours after they had received an accidental overdose of intrathecal methotrexate (median dose = 364 mg; range = 155-600 mg). Four of the seven patients had cerebrospinal fluid (CSF) exchange to remove methotrexate before CPDG2 administration.

Combination therapy in childhood leukaemia: in vitro studies of thiopurines and inhibitors of purine metabolism on apoptosis.

Background: Methotrexate (MTX) followed by 6-mercaptopurine (6MP) is one of the best known combinations for the treatment of childhood acute lymphoblastic leukaemia. Tiazofurin (TF) and 6-thioguanine (TG) are also used as chemotherapy agents in the treatment of malignancies. We have examined the induction of apoptosis by combinations of these drugs to gain more insights into their efficacy in the treatment of malignancies.

Conduct of phase I trials in children with cancer.

Purpose And Methods: Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies.

Determination of intracellular levels of 6-mercaptopurine metabolites in erythrocytes utilizing capillary electrophoresis with laser-induced fluorescence detection.

Capillary electrophoresis proved to be a useful technique for the analysis of intracellular levels of 6-thioguanosine mono-, di-, and triphosphate with analysis times of 20 min. Conditions required for baseline separation of the thioguanine nucleotides consisted of a 25 mM KH2PO4 (pH 8.0) buffer and a separation voltage of +28 kV.

Reversal of 6-mercaptopurine and 6-methylmercaptopurine ribonucleoside cytotoxicity by amidoimidazole carboxamide ribonucleoside in Molt F4 human malignant T-lymphoblasts.

Cytotoxicity of 6-mercaptopurine (6MP) and 6-methylmercaptopurine ribonucleoside (Me-MPR) was studied in Molt F4 human malignant lymphoblasts. Both drugs are converted into methylthioIMP (Me-tIMP), which inhibits purine de novo synthesis. Addition of amidoimidazole carboxamide ribonucleoside (AICAR) circumvented inhibition of purine de novo synthesis, and thus partly prevented 6MP and Me-MPR cytotoxicity.

Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study.

Purpose: Using the technique of recursive partitioning and amalgamation analysis with verification, the Pediatric Oncology Group (POG) investigated the independent prognostic significance of previously published prognostic factors significantly associated with event-free survival (EFS) in B-progenitor cell acute lymphoblastic leukemia (ALL).

Patients And Methods: Age, leukocyte count, sex, immunophenotype (expression of cytoplasmic immunoglobulin [Ig] and of surface antigens CD10 and CD34), and DNA index (ratio of the flow cytometry-determined DNA content of leukemia cells to that of normal diploid cells) were the variables used in the evaluation of four antimetabolite-based chemotherapy regimens in 1,535 children with the newly diagnosed B-progenitor cell ALL between February 1986 and May 1990.

Results: There were three subgroups at widely different risks of treatment failure.

Metastasizing chordoma in early childhood: a pathological and immunohistochemical study with review of the literature.

A 2 1/2-year-old female with a sphenooccipital-vertebral chordoma presented with neck pain, torticollis, fever, a lytic lesion of C2 vertebra, and bilateral nodular infiltrates in the lung. The lung biopsy revealed multiple tumor emboli by an enigmatic epithelioid-appearing neoplasm with immunohistochemical staining for vimentin, cytokeratin, and epithelial membrane antigen. A thorough roentgenographic evaluation disclosed a destructive, prepontine mass in the region of the clivus, erosion of the odontoid process, and compression of the cervical spinal cord.

Prolonged echoviral meningitis in a cancer patient with normal serum immunoglobulins.

This is a report of prolonged meningitis caused by echovirus type 20 in a patient with rhabdomyosarcoma. It represents one of the few documented cases of delayed clearance of echovirus in the cerebrospinal fluid in a patient with normal serum immunoglobulins. The case illustrates the prolonged clinical course of echoviral meningitis in a patient receiving cytotoxic drug therapy, and it suggests that factor(s) other than humoral antibodies may be involved in the elimination of echovirus from the central nervous system.

Pediatric Oncology Group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin's lymphoma (Burkitt's lymphoma excluded).

From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2-L2 therapy for the treatment of non-Hodgkin's lymphoma (NHL). Burkitt's lymphoma patients were ineligible; E-rosette-positive patients with greater than or equal to 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second-look surgery on completion of induction chemotherapy.

Management of children with isolated testicular leukemia.

Since 1975, nine children with testicular leukemia were treated at the University of Kansas Medical Center on a standard protocol. Six patients presented with overt testicular leukemia and three patients had microscopic testicular leukemia detected on a biopsy done after 3 years of continuous complete remission. All patients had an M1 bone marrow at the time of testicular relapse and one patient had a concomitant central nervous system (CNS) relapse.

Utilization of a human tumor cloning system to monitor for bone marrow involvement in children with non-hodgkin's lymphoma.

The objective of this study was to evaluate the sensitivity of two methods for determining bone marrow involvement with non-Hodgkin's lymphoma. These methods were histologic review of bone marrow aspirates, and clot sections versus in vitro growth of lymphoma colonies on soft agar. Forty-two bone marrow aspirates were studied from 14 children who were without bone marrow involvement at diagnosis.

In vitro sensitivity of normal granulocytic and lymphoma colonies to vinca alkaloids.

Recently, a colony-forming assay was developed in our laboratory for pediatric malignant lymphoid diseases. This assay supports the growth of lymphoma colonies (ML-CFC) as well as normal granulocytic colonies (CFU-C) and thus a direct comparison between the antineoplastic and myelosuppressive effects of a drug can be determined. To test specificity of this in vitro assay to structurally similar drugs, the inhibitory effects of three vinca alkaloids (vincristine, vindesine, vinblastine) on ML-CFC (B-, T-, pre-T-cell types) and CFU-C was determined.

Vindesine and prednisone for remission induction in children with acute lymphocytic leukemia.

Vinca alkaloids are effective anticancer agents. Vindesine is a recent vinca alkaloid derivative with anti-tumor effects shown in in vitro systems and in patients with acute lymphocytic leukemia (ALL). The present study was designed to investigate the therapeutic effectiveness and toxicity of vindesine in combination with prednisone for remission induction in late stage ALL in children.

Childhood cancer: nonmedical costs of the illness.

The financial burden of cancer treatment is a major source of anxiety for the families of pediatric cancer patients. Parents of these patients report that nonmedical, out-of-pocket expenditures are the most troublesome because, unlike medical bills, nonmedical costs must be paid immediately and are rarely reimbursed. Data on nonmedical expenditures (transportation, food, lodging, clothing, family care, and miscellaneous) were collected from 70 patients' families for one-week periods at three-month intervals.