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Biomedical subjects

G Spitzer

Publications and source records attributed to G Spitzer.

At least 127 records · Page 7Linked to original sources
PubMed1985

Differential cytotoxic activity of chemotherapy agents on colony-forming cells from human tumors and normal bone marrow in vitro.

We have compared the in vitro differential killing efficacy of doxorubicin, 5-fluorouracil, cis-platinum, etoposide, and bleomycin on human tumor cells in a new adhesive tumor cell culture system (ATCCS), and on normal bone marrow granulocyte-macrophage colony-forming units (GM-CFUC) in culture. All of the above chemotherapy agents were tested with continuous exposure against tumor cells and GM-CFUC. In addition, bleomycin was also tested with a short (60 min) exposure against GM-CFUC. In order to determine chemosensitivity against all five drugs, 48 tumor specimens from patients with heterogeneous tumor types were tested in the ATCCS. Each drug was tested at three different concentrations corresponding to their lethal doses against GM-CFUC. Our results show that all five drugs exhibited a dose-response relationship against tumor cells and GM-CFUC. Bleomycin also showed a pronounced GM-CFUC-sparing quality with 60-min exposure even at very high concentrations (86% survival of GM-CFUC at 10 micrograms/ml and 48% at 50 micrograms/ml). In addition, it has a high tumor response rate with continuous exposure at low concentrations (67% at GM-CFUC LD5 and 91% at LD40). These data suggest that the comparison of differential cytotoxicity of chemotherapy drugs between tumor cells and bone marrow cells may serve as a model to select agents suitable for in vitro chemotherapy of bone marrow for the purpose of autologous bone marrow transplantation. In particular, bleomycin appears very attractive and deserves further investigation.

Antineoplastic Agents↗
PubMed1984

High-dose chemotherapy with autologous bone marrow transplantation.

High-dose chemotherapy using drugs with predominant marrow toxicity and autologous bone marrow support has been investigated in a number of tumor types. High response rates are uniform and complete responses are also high; but long-term disease-free survival is occasional. This review discusses those tumor types where patients treated with this approach have survived disease free for several years. Also discussed is what other tumor types and prognostic subgroups of those tumors might benefit therapeutically from high-dose cytotoxic intensification with autologous bone marrow support or at least have this approach considered as the first alternative for initial relapse.

Antineoplastic Agents↗
PubMed1984

Evolution of oligoleukemia.

Chronic lithium administration to 22 patients with oligoleukemia did not alleviate cytopenia or stimulate bone marrow proliferative activity. The authors identified, however, pretreatment characteristics discriminating two evolutionary endpoints of oligoleukemia (marrow failure, 10 patients; overt acute leukemia, 12 patients): higher marrow leukemic infiltrate, normal myeloid precursor proportion, platelet count, and female sex all favored eventual transition to overt leukemia which, in comparison with marrow failure, was associated with a significantly longer survival duration from symptoms. For patients developing overt leukemia, survival from diagnosis was inversely correlated with the degree of marrow leukemic infiltrate. The lack of lithium responsiveness in oligoleukemia is consistent with the concept of differentiated leukemia with abnormalities either at the level of a lithium-responsive adherent cell elaborating colony stimulating activity (CSA) or at the level of CSA-responsive CFUs.

Acute Disease↗
PubMed1984

Dose-survival curves of cis-platinum, melphalan, and velban in human granulocyte/macrophage progenitor cells.

To optimize the in vitro concentrations of anticancer agents with clinical dose-limiting myelosuppression in the human tumor stem cell assay, we established dose-survival curves for cis-platinum, melphalan, and velban in normal human granulocyte/macrophage colony-forming units (CFU-gm) in a bilayer agar system. The LD50 (drug concentration capable of killing 50% of CFU-gm) of cis-platinum, melphalan, and velban for one-hour exposure was (a) greater than 10 micrograms/ml, (b) 0.9 microgram/ml, and 1.2 micrograms/ml, respectively. The respective values for continuous exposure were 0.3 microgram/ml, 0.12 microgram/ml, and 0.001 microgram/ml. The use of dose ranges based on bone marrow tolerance may influence the clinical value of in vitro tumor sensitivity studies of drugs with hematologic toxicity.

Antineoplastic Agents↗
PubMed1984

Responses of human bone marrow progenitor cells to fluoro-ara-AMP, homoharringtonine, and elliptinium.

The cytotoxicity of the investigational anticancer drugs fluoro-ara-AMP, homoharringtonine, and elliptinium on normal human granulocyte-macrophage colony-forming units in culture (GM-CFU) was investigated using a bilayer soft agar system. For each drug, the dose-dependent survival curve on a semilogarithmic plot formed a straight line. The D0 were: 0.51 microgram/ml (fluoro-ara-AMP), 0.004 microgram/ml (homoharringtonine) and 0.026 microgram/ml (elliptinium). The in vitro toxicity of drugs on bone marrow progenitor cells did not correlate with the relative myelosuppressive potency observed in vivo.

Alkaloids↗
PubMed1984

Repeated high-dose cyclophosphamide, BCNU and VP-16-213 and autologous bone marrow transplantation in adult acute lymphocytic leukemia in first remission.

In adult acute lymphocytic leukemia (ALL) cure is rare. The purpose of this study was to try to improve remission duration and survival by administration of two courses of high-dose chemotherapy, each followed by autologous bone marrow rescue, in first remission. Chemotherapy consisted of cyclophosphamide, BCNU and VP-16-213. Rescue bone marrow was fractionated over a discontinuous albumin gradient to minimize contamination with leukemic cells. Fourteen patients entered the study. Median total remission duration was 14 months. Three patients relapsed after one course of treatment. Five patients relapsed after the second course. Four patients died after the second course and two patients remain alive and well in unmaintained remission, with a total remission duration of 42+ and 47+ months. It is concluded that this regimen is toxic but, with careful selection of patients, may lead to long-term unmaintained remissions.

Adolescent↗
PubMed1984

Improved culture conditions for clonogenic growth of primary human breast tumours.

Four established human breast tumour cell lines with different biologic properties were selected for study and requirements for their clonogenic growth in semisolid cultures were identified. The conventional conditions were modified by factors that enhanced colony formation of 3 or more of these cell lines. The modified culture conditions were then applied to the growth in agar of primary breast tumours. A 5-fold improvement in plating efficiency was observed when cultures of 105 primary tumours grown under these modified conditions were compared to those of 52 tumours grown earlier under conventional conditions, and a 4-fold improvement resulted from the addition of hormones and conditioned medidum in 26 tumours cultured simultaneously under both conditions. The biologic relevance of these clonogens recovered in vitro was substantiated by a 70% concordance of in vitro and in vivo tumour sensitivity to anticancer drugs.

Agar↗
PubMed1984

Phase II clinical evaluation of dihydroxyanthracenedione in patients with advanced lung cancer.

A phase II clinical study of dihydroxyanthracenedione ( DHAD ) was conducted in 50 patients with advanced lung cancers. DHAD was administered intravenously on a 5-day schedule repeated every 4 weeks. Most patients had adenocarcinoma (46%), and had received previous chemotherapy (66%) and radiation therapy (50%). Among 41 evaluable patients, there were four partial remissions, eight disease stabilizations and 29 disease progressions. Remissions were more common among previously untreated patients (20% vs. 4%), particularly in patients with adenocarcinoma and large cell carcinomas of whom 3/10 (30%) responded. Responses lasted 9+, 9, 7, and 3 months, respectively. Cardiac toxicity was not observed. Other toxicities were tolerable. DHAD is a potentially useful agent for the therapy of adenocarcinoma and large cell lung cancers.

Adenocarcinoma↗
PubMed1984

Systemic combination chemotherapy as primary treatment of brain metastasis from lung cancer.

Five patients with primary lung cancer metastatic to the brain were treated with systemic combination therapy alone. One patient had had unsuccessful radiation therapy, while the other four received chemotherapy as the primary modality of treatment. Response was observed in all five patients. The concept of the blood-brain barrier and the role of systemic chemotherapy in metastatic cancer to the brain are discussed.

Adenocarcinoma↗
PubMed1984

Obstructive lung disease after allogeneic bone marrow transplantation.

We report the cases of 3 patients with marked dyspnea and an obstructive ventilation disorder associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation. This disorder was characterized by recurrent pulmonary infections and colonization of the lower respiratory tract by Pseudomonas aeruginosa. Two patients have shown rapidly progressive deterioration with death following due to respiratory failure. Intensive therapy with antibiotics, bronchodilators, high-dose steroids, and azathioprine was not effective in arresting the malignant course of this disorder.

Adult↗
PubMed1984

High-dose methylprednisolone treatment for acute graft-versus-host disease after bone marrow transplantation in adults.

High-dose methylprednisolone (HDMP) was used to treat 18 episodes of severe (grades III and IV) acute graft-versus-host disease (GVHD) that developed after allogeneic bone marrow transplantation in 12 patients with acute leukemia and in 2 with aplastic anemia. Most of the patients showed rapid improvement in GVHD, with complete resolution of the skin and gut manifestations. However, the response of liver disease to the treatment was slow and incomplete. Complications seen were interstitial pneumonia and fungal and viral infections. Seven patients survived for more than two months following the treatment of acute GVHD. Five of these became long-term survivors with a median survival of 22+ months (range 11-38 months); all five long-term survivors developed chronic GVHD and are alive at the time of this report. It appears that HDMP is an effective treatment for severe acute GVHD. However, its true efficacy can only be ascertained in a randomized study comparing high-dose and conventional-dose methylprednisolone.

Acute Disease↗
PubMed1984

The true predictive value of the human tumor stem cell assay: does a workable assay select for treatment responders?

In practice, the human tumor clonogenic assay is workable for less than half of the patient population to which it is applied, since the remainder of the specimens fail to produce sufficient numbers of colonies. Thereby a bias may be introduced which could result in a false predictive value positive of the test. It is therefore necessary to compare the responses to treatment of patients whose tumors could be assayed in vitro to those whose tumors failed to grow adequately, to assure that the prevalence of treatment responders has not changed within the group of patients for which the assay worked. From an analysis of the treatment response of 70 patients with stage III and IV ovarian carcinomas and 70 patients with stage IV breast cancer, no selection bias did occur and no preferential in vitro growth of tumor samples from patients with treatment response was found.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Low natural killer cell activity in the bone marrow of healthy donors with normal killer cell activity in the peripheral blood.

We have investigated the natural killer (NK) cell activity in peripheral blood and in bone marrow of nine normal donors. It was found that Ficoll-Hypaque (FH)-separated cells from the bone marrow collected in small (1 ml) aliquots had very low NK activity compared with normal activity in the peripheral blood of the same donor (mean +/- SD: 4.2% +/- 2.5% vs 25.1% +/- 15%, P less than 0.01). This difference was maintained for cells bearing receptors for sheep erythrocytes (E+) in both tissues (4.3% +/- 2.37% vs 15%+/-12.6%, P less than 0.01) or E- cells (2.5% +/- 2.86% vs 20.4% +/- 19.5%, P less than 0.01). Also, in bone marrow cells with Fc receptors for IgG (Fc gamma+) neither E+ nor E- had significant NK activity, in contrast to the peripheral blood, where significant NK cell activity was detectable in the Fc gamma + cells, either E+ or E- (1.9% +/- 1.2% and 1.3% +/- 1.4% vs 16.1% +/- 10.3% and 12.8% +/- 7.4%, respectively, P less than 0.01 for both). Our data indicate that bone marrow obtained with a low degree of blood contamination from normal donors has very low NK activity with no significant increase in any of the several fractions tested.

Bone Marrow Cells↗