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Biomedical subjects

B Leventhal

Publications and source records attributed to B Leventhal.

At least 37 records · Page 2Linked to original sources

Intermediate-dose intravenous methotrexate and mercaptopurine therapy for non-T, non-B acute lymphocytic leukemia of childhood: a Pediatric Oncology Group study.

Methotrexate (MTX) and mercaptopurine (MP) are the mainstays of continuation therapy for acute lymphocytic leukemia (ALL). These drugs are stored in tissues as active metabolites. Relapse in ALL might reflect failure to achieve adequate intracellular drug levels. Assured (parenteral) delivery of higher doses of MTX and MP should maximize tissue levels of these drugs by overcoming individual variations in absorption, metabolism, clearance, and compliance. Fifty-nine children with ALL at lower risk of relapse received 12 intensive MTX/MP courses immediately after 4 weeks of standard vincristine, prednisone, and asparaginase induction. Each 2-week intensive course included: MTX, 200 mg/m2 intravenous (IV) push then 800 mg/m2 IV over 24 hours on day 1; MP, 200 mg/m2 IV push then 800 mg/m2 IV over 8 hours on day 2; MTX, 20 mg/m2 intramuscularly on day 8; and MP, 50 mg/m2 orally daily on days 8 to 14. After the 6 months of intensive therapy, continuation therapy was weekly MTX/MP (as on days 8 to 14) for 1 or 2 years. Age-based MTX was given intrathecally (IT) for CNS prophylaxis. All patients entered remission. Three patients relapsed: bone marrow (at 24 and 37 months), and bone marrow and CNS (at 34 months). There were no isolated CNS relapses or deaths in remission. Event-free survival at 4 years is 94% (SE, 7%) by Kaplan-Meier analysis. Toxicities (infection, mucositis) occurred in less than 10% of intensive MTX/MP courses. However, a child with Down's syndrome withdrew after three courses because of recurrent severe mucositis. Further studies of this regimen are in progress.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical trial of etoposide (VP-16) in children with recurrent malignant solid tumors. A phase II study from the Pediatric Oncology Group.

Etoposide (VP-16), 150 mg/M2, given intravenously daily for 3 days every 3 weeks resulted in 3 complete responses and 6 partial responses in 154 patients with a spectrum of recurrent malignant solid tumors. There was evidence of disease control in an additional 37 patients (27 mixed responses and 10 stable disease). These responses occurred primarily in patients with Ewing's sarcoma, Hodgkin's disease, neuroblastoma and rhabdomyosarcoma. Most of the patients had every extensive prior therapy; however prior therapy with teniposide (VM-26), the congener of VP-16, did not seem to preclude responses to the latter drug. Myelosuppression was the principal form of toxicity. Neutropenia characterized by absolute neutrophil counts of 0.5 to 0.9 x 10(9)/L occurred in one-half of the patients, and thrombopenia with platelet counts of less than 25 to 49 x 10(9)/L in one-fourth. These results demonstrate a favorable therapeutic index for VP-16 in several recurrent childhood solid tumors, supporting its use as a component of primary therapy for these diseases.

Adolescent↗

Interferon alfa-n1 (Wellferon) in juvenile onset recurrent respiratory papillomatosis: results of a randomized study in twelve collaborative institutions.

Sixty-six patients with clinically severe juvenile-onset recurrent respiratory papillomatosis (RRP) were entered into a 12-month randomized crossover study to evaluate interferon alpha-n1 Wellferon (WFN) as an adjuvant to CO2 laser surgical excision. Eligibility required disease onset to be before age 16, and an endoscopic excision requirement of at least three operations in the 6 months immediately prior to entry. Patients were randomized to Observation versus WFN at a dose of 5 MU/m2 daily for 28 days and three times weekly for 5 months. The patient groups were comparable in extent of disease at entry. Total extent of disease was determined by a composite score derived from the number of diseased anatomic sites and extent of surface area and lumen encroachment present at each site. Standard endoscopic excisions were performed every 2 months and clinical courses compared on a basis of composite scores determined at each endoscopy. Statistically significant improvement occurred in the patient group which received WFN. We conclude that interferon alpha n-1 is an effective adjuvant to surgery in RRP management.

Adolescent↗

Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children.

We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other "sanctuary" areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation (P less than 0.01). The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group (8 of 120) (P = 0.01). Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate (P = 0.03); there was no difference in the rate of hematologic relapse. In both risk strata the frequency of testicular relapse was significantly lower in the methotrexate group (1 patient) than the radiation group (10 patients) (P = 0.01). Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation.

Adolescent↗

Open lung biopsy in the immunocompromised pediatric patient.

Rapidly progressive pulmonary distress occurs as a secondary complication in immunocompromised pediatric patients. These patients usually develop a pattern of diffuse alveolar and/or interstitial infiltrates on chest x-ray and pursue a rapidly downhill course despite intensive respiratory support with the use of multiple and varied antimicrobial regimens. These patients are subjected to diagnostic open lung biopsies to establish a diagnosis. The diagnostic value of open lung biopsy and its current impact on therapy is not clearly established. This retrospective study attempts to determine the impact of open lung biopsy on diagnosis and therapeutic outcome. Between November, 1974, and October, 1982, 40 diagnostic open lung biopsies were performed on immunocompromised patients with clinically progressive respiratory disease. Adequate follow-up for complete evaluation was possible in 34 of these patients. Most of these patients had hematologic malignancies and all were on chemotherapeutic drugs at time of open lung biopsy. Open lung biopsy was considered helpful, ie, resulted in a change in antimicrobial therapy or substantiated preoperative therapy, in 17 of our 34 patients (50%). A "treatable" condition, amenable to antimicrobial therapy, was diagnosed in 16 of our patients (47%). Pneumocystis carinii pneumonitis (PCP) was the most common diagnosis in 11 (69%) of our "treatable" patients. The remaining five "treatable" patients had sarcoidosis (1), histiocytosis X (1), bacterial pneumonitis (1) and fungal pneumonitis (2). No diagnosis was achieved by open lung biopsy in ten (30%) of our patients. There were two complications attributable to open lung biopsy (6%), including one death. All PCP patients treated with trimethoprim sulfamethoxazole (T/S) survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Monoclonal antibody characterization of surface antigens in childhood T-cell lymphoid malignancies.

Although childhood T-cell acute lymphocytic leukemia (T-ALL) and T-cell non-Hodgkin's lymphoma (T-NHL) have certain clinical features in common, T-ALL carries a notably poorer prognosis than does T-NHL. To determine whether the malignant cells from patients with these disorders are distinguishable, we examined bone marrow and/or blood from 51 children with T-ALL and tumor biopsy specimens from 17 with T-NHL, using a panel of monoclonal antibodies directed against T-cell differentiation antigens. We found considerable phenotypic heterogeneity in both T-ALL and T-NHL. Of the T-ALL (defined by greater than 25% blasts in the bone marrow) patients, 33% demonstrated a surface antigen pattern consistent with the earliest thymocyte stage of T-cell development (T9+ and/or T10+, or T6-/T4-/T8-/T3-), 37% were of a midthymocyte stage (T6+, and/or simultaneous expression of T4-helper and T8-suppressor antigens), and 30% expressed surface antigen patterns found on mature thymocytes (T3+, variable expression of other antigens). In contrast, tumor cell phenotypes in the 17 T-NHL patients were approximately equally distributed between mid- and mature thymocyte phenotypes. No NHL samples were classified as the early thymocyte phenotype. Clinical features as related to specific T-ALL immunophenotypes are presented, and the implications of these findings in regard to the current understanding of the differences in tumor biology between T-ALL and T-NHL are discussed.

Antibodies, Monoclonal↗

MER immunotherapy and combination chemotherapy for advanced, recurrent Hodgkin's disease. Cancer and Leukemia Group B study.

The effects of chemotherapy and chemoimmunotherapy in previously treated advanced Hodgkin's disease were evaluated in a randomized study of 167 patients by CALGB. Combination chemotherapy consisted of treatment with one of three regimens with further randomization of MER (methanol extraction residue BCG) immunotherapy or no MER during chemotherapy. CVPP (CCNU, vinblastine, procarbazine, prednisone) was compared to a new combination, BAVS (bleomycin, Adriamycin, vincristine, streptozotocin), and to a third regimen consisting of alternating cycles of CVPP and BAVS. At the current analysis there is no significant difference in complete responses among the chemotherapy regimens. MER did not improve complete response frequency and was associated with significantly poorer survival for patients previously treated with chemotherapy. There was also no benefit with MER for patients with at least one pretreatment positive skin test. Because of the documented lack of therapeutic benefit and the morbidity of painful ulcers, MER treatment has been discontinued.

Adult↗

The clinical utility of reproduction drawing tests with low IQ patients.

Bedside mental status testing in low IQ, poorly educated patients is often difficult. These patients, who comprise a significant proportion of the population served by major inner city public hospitals, have a limited ability to perform adequately on many higher cortical function tests. Because of this, it is often difficult to accurately differentiate between an organic brain syndrome and the effect of depressed intelligence in these patients. Copying line drawings and other constructional tasks are a very important element in a complete mental status examination, as they are frequently failed by patients with organic brain disease. The applicability of drawing tasks in the low IQ patient is an important issue; this study demonstrates that selected drawings can be effectively utilized to identify brain dysfunction in this low IQ population.

Brain Damage, Chronic↗

Cytogenetic studies in acute lymphocytic leukemia: special emphasis in long-term survival.

Cytogenetic studies were performed in 331 patients with ALL diagnosed at the National Institutes of Health between January 1961 and January 1976. Four patients had constitutionally abnormal genotypes, three had Down's syndrome, and one had a D/G translocation. Aneuploidy was observed in the pretreatment bone marrow in 49/115 (42.6%) of this series exhibited several general characteristics: aneuploid cells usually coexist with normal stem cells, hyperdiploidy is predominant and wide ranging aneuploidy clusters around a major cell line. The most common chromosomal group involved in aneuploidy is the G group (p=0.001) and the next most common is the B group (p=0.01). Aneuploidy disappeared after successful achievement of remission, and new clones developed in 12 patients during relapse. Two of the four patients originally thought to have a Ph1 chromosome, on trypsin Giemsa handing were proved to have a 21q- chromosome. A higher incidence of aneuploidy was noted in patients under one year or more than 20 years of age and was also higher in patients with low or elevated WBCs at diagnosis. The appearance of aneuploid cells in the bone marrow at the onset or later in the disease is of no prognostic significance but persistence of these lines and the development of total aneuploidy signals a poor prognosis. Eradication of aneuploid cells is therefore essential for the achievement of a long remission and progress to a permanent cure.

Adolescent↗

Human antisera detecting leukemia-associated antigens on autochthonous tumor cells.

Leukemia patients in remission were immunized with RAJI lymphoid tissue culture cell lines. Four of 7 patients developed antibody to the immunizing cell as well as to allogeneic leukemia cells. Sera from 3 patients were tested against autochthonous tumor cells either frozen or obtained at the time of disease relapse. Patient's sera were cytotoxic to their own leukemia cells; however, this cytotoxicity was lost at the time of relapse.

Antigens, Neoplasm↗