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Biomedical subjects

B G Leventhal

Publications and source records attributed to B G Leventhal.

At least 73 records · Page 4Linked to original sources
PubMed1978

Clinical implications of glucocorticoid receptors in human leukemia.

Glucorticoid receptors were studied in various populations of normal human peripheral blood lymphocytes and leukemic lymphoblasts. Normal lymphocytes contain low levels of glucocorticoid receptor (approximately 2,500 sites/cell) which are identical in T- and non-T-fractions. Phytohemagglutinin treatment increases levels about 3-fold. Leukemic lymphoblasts contain larger numbers of receptor sites. Presence of receptor is correlated with in vitro sensitivitiy to glucocorticoids and in vivo response to therapy. Quantity of receptor is also correlated with complete remission duration independently of leukemic cell type (T or null), initial WBC, or age of patient. Quantitative determination of glucocorticoid receptor levels in acute lymphoblastic leukemia may be of value both as an independent prognostic variable and in suggesting which patients should receive glucocorticoid therapy.

Adolescent↗
PubMed1977

Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy.

Two patients with acute lymphoblastic leukemia treated on the same protocol became blind during complete remission. Therapy consisted of systemic combination chemotherapy, prophylactic central nervous system irradiation and monthly intrathecal cytosine arabinoside. Eight months after CNS irradiation visual acuity in both patients began to decrease. Meningeal leukemia in the area of the chiasm was suspected but despite additional radiotherapy, steroids and continued intrathecal therapy, both patients were blind within 6 months. Numerous lumbar punctures were negative for leukemic cells. Extensive investigation, including craniotomy in one case, failed to reveal the cause of blindness. Biopsy of the optic nerve in one case was compatible with radiation toxicity. We postulate that potentiation of radiation toxicity to the optic nerves and chiasm by systemic chemotherapy, intrathecal chemotherapy, or both, may have led to blindness. The patients continue in complete hemotologic and CNS remission 12 and 29 months after becoming blind.

Acute Disease↗
PubMed1977

Multiple childhood osteosarcomas in an American Indian family with erythroid macrocytosis and skeletal anomalies.

Three of nine children of possibly consanguineous American Indian parents developed typical osteosarcoma in a 2-year period. Etiologic investigations detected limb anomalies and elevated mean corpuscular volumes (98--109 micrometer3) in the surviving tumor patient, several of her sibs, and her father. Limb anomalies included simple clinodactyly with brachymesophalangy, absence of one digital ray of the foot, and bilateral radioulnar synostosis. The red cell macrocytosis was not accompanied by anemia or explained by the usual causes. No unusual environmental exposures were found and screening for possible oncogenic viruses by culture, electron microscopy, and serology was negative. All family members had elevated antibody titers to Epstein-Barr viral antigens. The proband and her father had excessive chromosomal breaks in the bone marrow. This unusual familial pattern of osseous malignancy and malformation and defective erythropoiesis, tentatively called OSLAM syndrome, may represent impaired regulation of bone development.

Adolescent↗
PubMed1976

Effects of childhood leukemia and chemotherapy on puberty and reproductive function in girls.

Longer survivial in childhood leukemia prompted this study of pubertal development and reproductive function in 35 girls and women. Twenty-eight patients (80 per cent) had normal pubertal progression during a median of 74 months after diagnosis of leukemia and 49 months of chemotherapy. Seven patients were abnormal: four exhibited hypothalamic-pituitary dysfunction with suppression of circulating serum gonadotropins (less than 6 mlU per milliliter); three others had evidence of primary ovarian dysfunction - reversible in two - with inappropriately elevated circulating serum gonadotropins (follicle-stimulating hormone greater than 20 mlU per milliliter). Normal sexual development correlated best with pubertal status at onset of leukemia; only one of 17 patients with diagnosis before puberty experienced altered pubertal progression, whereas abnormalities appeared in six of 18 with onset during puberty or after menarche. Thus, most girls with aggressively treated child-hood leukemia have an excellent prognosis for normal hypothalamic-pituitary-ovarian function; normal development is further enhanced in patients who are prepubertal at onset of leukemia.

Adolescent↗
PubMed1976

Combined modality treatment of American Burkitt's lymphoma.

Fifteen American patients with Burkitt's lymphoma were treated in a clinical trial employing chemotherapy, radiotherapy, and immunotherapy. Two patients died during induction, and 13 achieved complete responses. Eight patients relapsed at a median of 11 weeks from initial treatment, and seven of these have died. The remaining patient has enjoyed a prolonged third remission following intensive chemotherapy and bone marrow autograft. Five patients remain in their first remission in excess of 1 year. The major therapeutic goal in the management of Burkitt's lymphoma is the prevention of relapse; the identification of risk factors and various strategies to achieve this goal are discussed.

Adolescent↗
PubMed1976

Acute myelogenous leukemia in children: a preliminary report of combination chemotherapy.

Twenty-four children (2 to 21 years) diagnosed as having AML from 1969 to 1972 were randomized to receive either a single combination (COMP or PRAVD) or sequential combination chemotherapy (alternating POMP and PRAVD). Seventeen achieved complete remission. Patients who received POMP alone had the longest median duration of remission (1,400 days) compared to PRAVD (395 days) or POMP-PRAVD (270 days); interpretation of this difference is uncertain, since the numbers in each group are small. Fifteen patients have relapsed, four initially with CNS involvement. Successful reinduction was achieved almost exclusively for patients who had initially received POMP. Survival after first relapse was short. Patients less than 16 years had a median survival of 632 days, compared to 285 days for patiens greater than 16 (p less than 0.05). The high initial induction rate in these patients is encouraging, but the duration remission is inferior to that seen in childhood ALL. Moreover, the slope of the relapse curve is continuous over a five-year period with no definite plateau where it might appear that patients are no longer at risk of relapse. Improved methods for the treatment of childhood ALL and adult AML suggest possible new approaches to AML in children, with prophylactic treatment of central nervous system, late intensification, and immunotherapy.

Adolescent↗
PubMed1976

Reversible dementia temporally associated with intraventricular therapy with methotrexate in a child with acute myelogenous leukemia.

During maintenance therapy with intraventricular methotrexate, progressive dementia developed in a child with meningeal leukemia. Cerebrospinal fluid levels of MTX were in the nontoxic range and neurologic evaluation failed to demonstrate anatomic obstruction, infection, or folate depletion. The patient's symptoms gradually resolved when the methotrexate was discontinued, suggesting that methotrexate neurotoxicity may occur in the absence of an elevated CSF concentration of MTX.

Child, Preschool↗
PubMed1976

Lack of prognostic value of lymphoblast size in acute lymphoblastic leukaemia.

There are conflicting reports about the relationship of cell size and type to prognosis in acute lymphoblastic leukaemia (ALL). For this reason, bone marrows at diagnosis and first relapse were studied in 56 children with ALL treated on the same protocol. Lymphoblasts greater than 12 mmu in diameter were called macrolymphoblasts (MLB). Forty-one of 56 initial bone marrows had less than 20% MLB(group A), and 15 had greater than 20% MLB (group B). Median survival, complete remission rate, first remission duration, and the distribution of CNS leukaemia were similar in both groups. First relapse marrows were examined from 50 patients and a significant increase in MLB compared to initial pre-treatment bone marrows (18% vs 8%) was found.

Adolescent↗
PubMed1975

New looks in leukemia.

Immunologic markers are now available for acute leukemia. These show that most patients now diagnosed as having acute lymphatic leukemia have blast cells which react with antihuman T antisera. In addition, about 20% of patients have blast cells which form E rosettes. These patients tend to be those with high white counts and aggressive disease. Tumor-associated antigens have been identified in acute leukemia. Antisera raised in other species by immunization appear to detect some antigens common to all acute leukemias and other antigens which can distinguish the myeloid from the lymphoid leukemias. The reactivity to leukemia antigens can be related to prognosis. The immune manipulations required to produce cure, however, are not understood. These antigenic markers, by allowing us to detect smaller amounts of tumor than can be detected by morphology alone, may help us to predict relapse and define cure.

Animals↗
PubMed1975

Long-term second remissions in acute lymphatic leukemia.

Long-term second remissions were seen in 5/66 patients with all. Relapse was extramedullary in 2/5. Persistent, progressive marrow lymphocytosis preceded relapse in 4/5 patients and persistent marrow eosinophilia in 1/5. All 5 patients had had an unmaintained remission of at least 6 months prior to relapse, and responded the second time to drugs which were essentially the same as those used initially. We conclude that long-term second remissions may occur in all. Patients who relapse after 6 months or more of unmaintained remission should be treated with the drugs used in current initial induction regimens in hope of cure.

Adolescent↗
PubMed1975

Varied manifestations of a familial lymphoproliferative disorder.

In a sibship of nine adults, four died of lymphocytic or histiocytic lymphomas, and one of Waldenström's macroglobulinemia (immunoglobulin M [IgM], kappa type) complicated by adenocarcinoma of the lung. In the next generation, one member died of Hodgkin's disease; four of nine healthy persons had impaired lymphocyte transformation in vitro in response to phytohemagglutinin-P (PHA-P), and three of these had polyclonal elevations in IgM levels. Subsequent to these observations, adenocarcinoma of the lung developed in one woman with immune defects, and lymphocytic leukemia developed in her 3 year old grandson. The findings in this family point to a genetically regulated defect of immunity expressed as diverse lymphoproliferative disorders, including polyclonal and monoclonal IgM gammopathies. The occurrence of pulmonary adenocarcinoma in two members suggests genetic and immunologic determinants in these instances.

Adenocarcinoma↗
PubMed1975

Cell-mediated immunity in human acute leukemia.

The general cell-mediated immunological reactivity of patients with acute leukemia has been found to be intact, although it may be depressed by extensive disease or by chemotherapy. Patients with acute leukemia also have cellular immune reactivity against tumor associated antigens, as measured by skin tests for delayed hypersensitivity, lymphocyte stimulation, and 51Cr release cytotoxicity. Skin reactions to autologous and allogeneic crude membrane extracts of blast cells correlated with disease state, positive in many patients in remission and negative in most patients in relapse. Extracts of human lymphoid tissue culture cell lines derived from lymphomas or leukemia also gave positive reactions in patients with acute leukemia, and also in patients with lymphoma and nasopharyngeal carcinoma. The antigens detected in the skin tests with the lymphoid cell lines appear to be different from those associated with Epstein-Barr virus (EBV) and from those detected in the 51Cr release assay. Evidence is presented which suggests a complex variety of antigens on blast cells and on the cell lines. Although leukemia associated antigens were also detected by lymphocyte stimulation and by cytotoxicity assays, the results did not correlate with the skin tests nor with each other. The possible use of these assays for monitoring the chemotherapy and immunotherapy of acute leukemia patients is discussed.

Acute Disease↗