Search PubMed⌕ Search

Biomedical subjects

B G Leventhal

Publications and source records attributed to B G Leventhal.

At least 55 records · Page 3Linked to original sources

Glucocorticoid receptors in immunological subtypes of childhood acute lymphocytic leukemia cells: a Pediatric Oncology Group Study.

Glucocorticoid receptors were quantitated by a whole cell method in cells from 593 children with acute leukemia at the time of diagnosis. Leukemia cells were also immunologically typed and divided into early pre-B- (not reactive with antibodies to T-lymphocyte antigens, surface immunoglobulin-negative, cytoplasmic immunoglobulin-negative), pre-B- (not reactive with antibodies to T-lymphocyte antigens, surface immunoglobulin-negative, cytoplasmic immunoglobulin-positive), B- (not reactive with antibodies to T-lymphocyte antigens, surface immunoglobulin-positive), and T- (reactive with antibodies to T-lymphocyte antigens) subtypes. There was a median of 9.7 X 10(3) sites per cell in the 359 with early pre-B-acute lymphocytic leukemia, a median of 8.1 X 10(3) sites per cell from 103 patients with pre-B-cell leukemia, and a median of 4.0 X 10(3) sites per cell from 116 patients with T-cell leukemia. The distributions per cell were significantly different among these 3 groups (P less than 0.0001). The 15 patients with B-cell disease had a median of 3.2 X 10(3) sites per cell. At the time of analysis, remission induction data are available for most of these patients. Within the early pre-B- group 291 patients with a median receptor number of 9.9 X 10(3) achieved remission, while 13 with a median receptor number of 4.8 X 10(3) did not. These distributions were significantly different (P = 0.034). Within the pre-B- and T-cell groups the distributions of receptor numbers for responders and non-responders were not significantly different. We conclude that each immunological subtype has characteristic receptor distribution. High receptor number within the null group is associated with the ability of the patient to achieve remission; however, the range of values within each patient group is too broad to use this assay as a predictor of response for any individual patient.

Adolescent↗

Recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis is a disease caused by a virus in the Papovaviridae family. It tends to recur in the laryngotracheal tree, and treatment is surgical removal with a CO2 laser and suspension microlaryngoscopy. Some patients may require these procedures every few weeks, and a systemic agent to control disease would be ideal for them. Care must be taken in the selection of an agent, as these lesions, similar to other papova virus-induced lesions, are most susceptible to malignant degeneration in the presence of a carcinogen. Eight patients were given 10 courses of polyriboinosinic-polyribocytidylic acid [poly(I,C)-LC] in an attempt to control their disease. The three who were tested were able to produce good titers of interferon. The rate of disease progression was probably slowed in four patients, as reflected by a decrease in the requirement for surgery; however, the medication appeared to be relatively toxic in effective doses. Four of 10 courses were held for hepatotoxicity, and mild hepatotoxicity occurred in four more. One course was held for thrombocytopenia associated with bleeding at the tracheostomy site. We conclude that in its presently available form, poly(I,C)-LC is too toxic to be administered long term for control of this disease.

Adult↗

Comparison between x-ray and bone scan detection of bone metastases in patients with rhabdomyosarcoma.

A comparison of radiographic and 99mTechnetium methyldiphosphonate scintigraphic evaluations for extent of skeletal disease was made retrospectively in 17 pediatric patients with Group III and IV rhabdomyosarcoma. Thirteen children had evidence of skeletal metastases. Of these, four exhibited multiple sites of blastic as well as lytic skeletal involvement on x-rays that were not detected by bone scans: two at the time of initial diagnosis, and two at relapse in children with prior radiotherapy to involved bones. In three additional patients a greater extent of bony disease was evident on x-rays than on bone scan. Neither the pathology of the tumor, lytic versus blastic quality of the bone lesion, nor lesion size per se was found to correlate with the failure to detect them on the bone scan. Although bone scans have greater sensitivity than x-rays for the detection of metastatic bone involvement in several adult and pediatric neoplasms, in the case of rhabdomyosarcoma, the radiographic exam appears to be a more sensitive indicator in some patients and should be considered an essential study in the evaluation of skeletal involvement by this tumor.

Bone Neoplasms↗

Magna-field irradiation and autologous marrow rescue in the tratment of pediatric solid tumors.

Marrow ablative therapy has been given to pediatric patients with a variety of disseminated tumors. Eight patients with advanced neuroblastoma received autologous marrow reinfusion after intensive therapy. Three of eight are in continus complete remission for 7 to 60 months. An additional four patients received allogeneic marrow transplantation and two remain in continuous complete response at 21 and 39 months. Intensive therapy and autologous marrow reinfusion have been applied to Ewing's sarcoma, but only preliminary results are available. Six patients with disseminated rhabdomyosarcoma and extra-osseous Ewing's sarcoma received conventional chemotherapy followed by sequential hemi-body irradiation. Four of six patients received autologous marrow rescue. Their median disease-free survival is 17 months. This preliminary experience demonstrates the feasibility of using marrow ablative therapy with autologous marrow transplantation in the treatment of pediatric solid tumors. Continuing Phase II studies are required to substantiate its efficacy.

Adolescent↗

Prognostic role of the intravenous urogram in children with acute leukemia.

We retrospectively studied intravenous urograms (IVU) performed at presentation on 108 children with acute leukemia in order to determine whether any association existed between an abnormal IVU and known prognostic factors at presentation, initial renal function, and outcome. Sixteen patients (14%) had abnormal IVUs. These patients were compared to the remainder of the group and found to be comparable in respect to known prognostic factors at diagnosis (P greater than 0.05). No correlation was found between abnormal renal function and an abnormal IVU. Renal enlargement was associated with shorter survival only in patients who had both adenopathy and hepatosplenomegaly (P less than 0.01). This effect did not persist in any other group of patients examined. When subjected to multivariate analysis the IVU did not significantly influence relapse or survival in these patients. Renal enlargement may be a prognostic feature in some patients with childhood leukemia. Nevertheless routine evaluation by IVU is discouraged because of potential adverse affects of urographic contrast media and the availability of noninvasive ultrasound techniques.

Adolescent↗

Cisplatin therapy in recurrent childhood brain tumors.

Twenty-two patients with brain tumors were initially treated with surgery, radiation therapy, and/or adjuvant chemotherapy. Histologic diagnosis included 11 gliomas, seven ependymomas, one dysgerminoma, one teratocarcinoma, one pinealoma, and one small cell tumor. At recurrence, documented on computerized tomographic scan, cisplatin (60 mg/m2/day iv X 2) was given every 3-4 weeks. Seventeen patients received two or more courses and were considered to be evaluable for response. Response parameters included change in the size of tumor on computerized tomographic scan and/or in clinical findings. Four patients had complete response, five had partial response, four had stable disease, and four had disease progression. Toxic effects were manageable. The number of patients with grade 3-4 toxic reactions, by category, were: thrombocytic, ten; leukocytic, four; renal, five; metabolic, four; gastrointestinal, none; and neurologic, seven. Two of the 14 patients tested had grade 3-4 ototoxicity. Acute fluid retention with decreased serum electrolytes and serious but reversible changes in the mental status, which were experienced in earlier patients, decreased in severity with increasing experience of the investigator. In summary, cisplatin appears to be active in a spectrum of brain tumors and should be studied further for therapeutic efficacy.

Adolescent↗

Immunotherapy of sarcomas.

Numerous attempts have been made at immunotherapy of sarcomas in man, and in most of these, tumor cells were used as a source of antigen. The cells were given by direct immunization with an adjuvant such as BCG or in adoptive immunotherapy trials in which tumor-immunized donors were a potential source of immune cells. These series of studies have shown consistent evidence of effect on the immune response of the patients to tumor antigens but no consistent clinical effect. Nonspecific immunotherapy has been less vigorously explored, but a current trial with interferon is potentially promising. The immune response to tumor antigens is surely a complex system of checks and balances. The methods investigators have used to date may have stimulated suppressor responses as well as or more effectively than cytotoxic responses to tumor. More precise immune modulation may indeed result in an effective antitumor response in man.

Animals↗

Glucocorticoid receptors in lymphoid tumors.

There is a range of levels of glucocorticoid receptor numbers seen in the various subclasses of acute lymphatic leukemia (ALL). This variability cannot be explained by the known correlation between active cell proliferation and an increase in the number of receptors, since the tumors with the highest growth fraction (i.e., Burkitt's lymphoma and T-cell leukemia) tend to have lower average receptor numbers than do tumors with lower growth fractions such as common ALL. All clinical specimens from patients with lymphatic leukemia have some measurable level of glucocorticoid receptors; therefore, the resistance seen in vivo cannot be explained by the lack of receptors. However, there has been a positive correlation, in our hands, with receptor level and prognosis. On the basis of in vitro models, it is proposed that perhaps the high receptor cell lines (i.e., common ALL of childhood) have relative stability of their genetic material making glucocorticoid-resistant mutations less likely to occur in patients with these cells than in low-receptor cell lines (i.e., T-cell leukemia). This greater genetic variability in the low-receptor lines could account for the earlier emergence of clinical glucocorticoid resistance in these patients.

Animals↗

Ovarian involvement in neuroblastoma.

A case of neuroblastoma involving the ovaries bilaterally at diagnosis is reported. A review of previous cases of neuroblastoma at Johns Hopkins Hospital revealed no previous occurrence of ovarian metastatic disease at diagnosis, but involvement in about one-third of cases at autopsy. This appears to be a more common site of metastatic disease than has been previously recognized. The significance of this site of metastases in neuroblastoma is unknown.

Adrenal Gland Neoplasms↗

Human B-cell antigens in acute lymphocytic leukemia. Lack of correlation with other lymphocyte surface markers.

Cells from patients with acute lymphocytic leukemia were studied for cell surface markers and B-cel alloantigens. Three cell types were defined. Those spontaneously rosetting with erythrocytes and not prossessing surface immunoglobulin or complement receptors were considered T-cells. Cells not showing rosette formation, surface immunoglobulin, or complement receptors were considered null cells and could be divided into two categories based on their ability to stimulate in mixed lymphocyte reaction. B-cell alloantigens were found randomly distributed on all cell types. The results suggested that genetic information for human B-cell antigens was present in all cell types and that other cell surface markers may reflect a stage of differentiation of the leukemia cell type.

Antigens, Surface↗

Cryopreserved autologous bone marrow transplantation in the treatment of selected pediatric malignancies: a preliminary report.

We have shown that it is possible to collect and viably store sufficient numbers of stem cells to hematologically reconstitute patients following marrow-lethal doses of chemoradiotherapy. While no current procedure can be guaranteed to eliminate clonogenic tumor from the bone marrow, the fact that hematopoietic stem cells capable of reconstituting the host can be obtained after intensive chemotherapy makes it possible to clear microscopic foci of tumor from the marrow prior to storage. Such patients are now included in our protocol. The initial treatment results indicate that, in selected circumstances, tumor in otherwise refractory patients can be eliminated or partially controlled by a single intensive pulse of chemoradiotherapy with severe but acceptable extramedullary toxicity. The fact that patients can be rescued from otherwise lethal myelotoxicity by the reinfusion of cryopreserved autologous bone marrow permits wider exploration of new, more intensive cytoreductive regimens in a variety of cancers.

Bone Marrow Transplantation↗

Autologous bone marrow transplantation in the treatment of selected human malignancies: The Johns Hopkins Oncology Center Program.

Preliminary clinical trials using cryopreserved autologous bone marrow reinfusion have now been carried out at our institution in 5 children and 2 adults with advanced stages of neuroblastoma, rhabdomyosarcoma, non-Hodgkin's lymphoma and small cell carcinoma of the lung. Normal numbers of in vitro colony forming cells (CFU-C) were obtained from these patients despite prior courses of combination chemotherapy. The dose of marrow cells cryopreserved ranged from 1-6 X 10(8) cells/kg and recovery of CFU-C after thawing averaged 50%. Partial or complete hematologic reconstitution was achieved in all patients. The time for recovery ranged from 10-43 days for leukocytes (greater than 1000 cells/mm3) and 23-45 days for platelets (greater than 50,000/mm3). Two patients have died of interstitial pneumonitis due to cytomegalovirus. Three patients have died of recurrent tumor at 40, 48 and 156 days post-transplant. Two patients have had significant therapeutic benefit. One of these had a stable partial response permitting the use of further post-transplant therapy and is alive and well 16+ months post-transplant. The other patient had a complete response and remains tumor-free 25+ months following therapy. We conclude: 1) Autologous bone marrow reinfusion permits hematologic reconstitution following marrow-ablative therapy. 2) A quantity of marrow sufficient for this purpose remains viable following cryopreservation even when obtained from patients previously exposed to chemotherapy. 3) Autologous bone marrow reinfusion now allows the exploration of more intensive cytoreductive therapy in selected malignancies.

Antineoplastic Agents↗

Correlation of adenosine deaminase activity with cell surface markers in acute lymphoblastic leukemia.

Adenosine deaminase (ADA) activity has been measured in the lymphoblasts of 23 untreated patients with acute lymphoblastic leukemia and related to the presence or absence of immunologic cell surface markers. The mean ADA activity in the acute lymphoblastic leukemia population as a whole was increased fourfold over that in normal lymphocytes. 9 of the 23 patients were classified as thymus-derived (T-) cell acute lymphoblastic leukemia on the basis of erythrocyte rosette positivity; the remaining 14 patients had null-cell leukemia. The mean ADA activity (ADA U/mg protein) of T-cell lymphoblasts (102 U) was 3 times higher than the mean of null lymphoblasts (30 U). This difference is statistically significant (P less than 0.02). Measurement of ADA activity offers a biochemical method of distinguishing between immunological subtypes of lymphoblasts which may be of prognostic and therapeutic value.

Adenosine Deaminase↗