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T J Moss

Publications and source records attributed to T J Moss.

At least 55 records · Page 3Linked to original sources
PubMed1992

Quantitation of tumor cell removal from bone marrow: a preclinical model.

We have developed a multiassay system consisting of fluorescence microscopy, immunocytology and tumor colony assay to monitor the removal of tumor cells from bone marrow. This system was tested in preclinical purging experiments in which neuroblastoma cells were seeded into bovine marrow and purged by treatment with monoclonal antibodies and immunomagnetic beads. Eight experiments were performed on two different neuroblastoma cell lines seeded at 2% and/or 5% contamination. We consistently demonstrated greater than a 3 log removal with one cycle of antibody/bead treatment and greater than a 1 log further reduction by addition of a second cycle. We also demonstrated removal of all detectable tumor stem cells by this purging method. We feel that this system will prove valuable for monitoring ex vivo tumor removal in future clinical studies and should be considered for use in other purging trials.

Animals↗
PubMed1991

Serial immunocytologic analysis of blood for tumor cells in two patients with neuroblastoma.

Tumor surveillance tests are used to determine whether malignant cells are responsive or resistant to therapeutic regimens. For patients with neuroblastoma, conventional methods of surveillance are not sensitive enough. Because tumor cells are shed into the circulation, immunocytologic analysis of blood may function as a sensitive monitoring system. In this study, five blood samples were obtained from two patients with disseminated neuroblastoma at diagnosis and during therapy. These samples were analyzed with monoclonal antibodies and immunoperoxidase staining to determine whether circulating neuroblasts were present. In both patients, the presence or absence of circulating neuroblasts yielded information that was more sensitive than that from conventional tests. The authors conclude that immunocytologic analysis of blood should be included with conventional monitoring methods for surveillance of patients with disseminated neuroblastoma.

Antibodies, Monoclonal↗
PubMed1991

Prognostic value of immunocytologic detection of bone marrow metastases in neuroblastoma.

BACKGROUND: Morphologic evaluation of bone marrow for neuroblastoma cells is a routine and important component of clinical staging. Specific immunostaining of malignant cells with monoclonal antibodies should be more sensitive, however, and may improve the detection of metastases and provide additional prognostic information. METHODS: We looked for tumor cells in bone marrow from 197 patients with newly diagnosed neuroblastoma, using immunoperoxidase staining with monoclonal antibodies (immunocytologic analysis) and examination of smears and specimens obtained by trephine biopsy (conventional analysis). RESULTS: Routine smears and trephine-biopsy specimens were positive for tumor cells in 46 percent of the patients, whereas 67 percent were positive on immunocytologic analysis (P less than 0.0001). Immunocytologic analysis detected bone marrow metastases in 34 percent of patients considered to have only localized or regional disease (Stage I, II, or III). It also identified tumor cells that were not detected by conventional analysis in patients with widespread disease (Stage IV or IVS). Tumor content, as determined by immunocytologic analysis, predicted clinical outcome in relation to the age of the patient at diagnosis. Patients with Stage II or III disease diagnosed after one year of age who did not have occult marrow metastases did well, whereas those with metastases did poorly (P = 0.006). Patients in whom Stage IV disease was diagnosed before they were one year of age did well if bone marrow metastases were few or absent, but had poor survival if the marrow contained more than 0.02 percent tumor cells (P = 0.03). CONCLUSIONS: Immunocytologic analysis of bone marrow aspirates is more sensitive than conventional analysis in detecting tumor cells and provides prognostic information. The relations among marrow metastases, age at diagnosis, and clinical outcome illustrate the biologic heterogeneity of neuroblastoma.

Age Factors↗
PubMed1990

Contamination of peripheral blood stem cell harvests by circulating neuroblastoma cells.

Peripheral blood stem cells (PBSC) are being used as one alternative to autologous marrow rescue for patients with neuroblastoma and other solid malignancies. Some physicians prefer use of PBSC because less risk of tumor contamination is believed to exist. This hypothesis was evaluated by immunocytologic analysis of blood samples and concurrently drawn bone marrow (BM) samples and of PBSC harvests obtained from 31 patients with disseminated neuroblastoma. We found circulating neoplastic cells in 75% of specimens analyzed at diagnosis, in 36% during therapy, and in 14% of PBSC harvests. Tumor cells in blood obtained during therapy did not appear until 3 months after the time of diagnosis. Clearance of circulating neuroblastoma cells was documented after two courses of induction chemotherapy. Six of 13 patients with minimal or no BM disease had positive blood specimens. We conclude that substantial risk of tumor contamination of PB harvests exists and recommend that induction chemotherapy be administered before hematopoietic progenitor cells are collected from blood.

Adolescent↗
PubMed1990

Detection of neuroblastoma cells in blood.

Tumor surveillance tests are used to detect relapse and to guide the clinician in making therapeutic changes. Identification of relapse early in the course of disease may improve long-term survival. For patients with neuroblastoma, current conventional surveillance methods include radiologic testing, bone marrow analysis, physical examination, and measurement of urinary catecholamine metabolites. Immunocytologic analysis of blood for the detection of circulating tumor cells is a highly specific and sensitive method, which may prove useful in monitoring patients with neuroblastoma. In our study, circulating tumor cells were detected in seven of 10 patients with known disseminated disease at diagnosis and in six of 13 patients during therapy. In some patients, as few as two tumor cells were identified among 100,000 normal hematopoietic cells. The presence or absence of circulating neuroblasts in the 13 patients evaluated during therapy was significantly correlated with tumor relapse (P = .002). We conclude that immunocytologic analysis of blood is a sensitive method for the detection of circulating neuroblasts. We recommend that this technique be used in conjunction with other conventional methods for improved tumor detection and subsequent monitoring of neuroblastoma patients.

Antibodies, Monoclonal↗
PubMed1989

Accuracy of diagnostic imaging as determined by delayed operative intervention for advanced neuroblastoma.

Current treatment of newly diagnosed widespread neuroblastoma may include chemotherapy, delayed surgical resection, marrow ablative chemoradiotherapy, and bone marrow transplantation. Diagnostic imaging (DI) with computerized tomography (CT) or magnetic resonance imaging (MRI) has been used to determine response to therapy and timing of delayed resection. We assessed the accuracy of DI in 25 patients (26 total cases) treated over 21 months. Tumor size and location were estimated prior to surgical resection by DI, and the sensitivity and specificity of these studies were determined from operative findings. DI consisted of CT (15), MRI (8), and MRI and CT (3). Discordance between DI and operative findings was found in ten patients (38%). This included three errors of sensitivity (12%), including two false-positives and one false-negative. Seven errors of specificity were noted; they included a positive scan with no viable tumor identified (3), much more extensive disease (3), or less extensive disease (1). Viable tumor was identified in 18 cases, and in 11 patients, complete resection of macroscopic tumor at the primary site was carried out. Ten of 13 patients operated on within 5 months of beginning chemotherapy were rendered grossly free of neuroblastoma at the primary site after surgery. Eight of 12 patients operated on 6 months or longer after starting chemotherapy were rendered grossly free of tumor at the primary site. Bone marrow transplantation was performed in 21 patients, ten of whom are alive with a median follow up of 20 months. Survival was similar for patients who underwent surgical resection at less than or equal to 5 v greater than 6 months after starting chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗
PubMed1989

Clinical collection and use of peripheral blood stem cells in pediatric patients.

Peripheral blood stem cells have been used in lieu of marrow as autologous cellular support after marrow-ablative radio/chemotherapy. Autologous marrow support allows the use of higher, more effective doses of therapy. Peripheral blood stem cells (PBSC) offer the potential for this form of "transplant" in patients with marrow involved with disease. PBSC use also allows the avoidance of marrow harvest under general anesthesia. Previous reports of PBSC use have been limited to adults. This article describes peripheral blood stem cell collection in children, and documents the successful use of such cells in a 21/2-year-old boy and a 3-year-old girl with progressive stage IV neuroblastoma involving the marrow. Collections were performed using a Fenwal CS3000 blood cell processor primed with fresh frozen plasma and red cells, using a low flow rate to avoid citrate toxicity. The transplant was performed using collections that were negative or low in neuroblastoma cells (as detected by anti-neuron-specific enolase and antineuroblastoma monoclonal antibodies) after preparation with high-dose cyclophosphamide, etoposide, and cisplatin. Posttransplant recovery was uneventful, and engraftment was comparable to that in 4 patients treated with a similar preparative regimen followed by infusion of autologous marrow. Using careful technique, PBSC support in lieu of marrow may be a viable treatment modality in pediatric neuroblastoma or other solid tumors, particularly when the marrow is involved with disease.

Blood Transfusion, Autologous↗
PubMed1989

Secondary leukemia following successful treatment of Wilms' tumor.

Leukemia accounts for 15-20% of the secondary malignancies among survivors of Wilms' tumor. We report three patients who developed leukemia after the successful treatment of Wilms' tumor, each of whom demonstrates the importance of close long-term medical surveillance. The first patient developed Philadelphia chromosome positive chronic myelogenous leukemia (CML) 6 years after the diagnosis of Wilms' tumor. This is the second report of CML occurring after Wilms' tumor. The other two patients developed acute nonlymphocytic leukemia (ANLL) 3 and 18 years after successful treatment of Wilms' tumor. In one patient, the clinical manifestations were subtle, and in the other the latency period was the longest reported for secondary leukemia following Wilms' tumor. We conclude that survivors of childhood cancer require frequent medical surveillance even in their adult years.

Alkylating Agents↗
PubMed1988

Expression of a developmental stage-specific antigen by neuronal precursor cells of human fetal cerebellum.

A monoclonal antibody that was prepared against human neuroblastoma cells was shown to react strongly with fetal brain and moderately with adult brain by quantitative absorption testing. Immunoperoxidase staining demonstrated expression of the antigen by neuronal precursor cells in the cerebellar external granular layer of a 24- to 26-week fetus but not by their mature derivatives in the granular and molecular layers of adult cerebellum. The antigen was also present on subventricular cells of fetal cerebral cortex, as well as adult and fetal astrocytes. The expression of this antigen by neuronal precursor cells in the external granular layer but not their mature derivatives suggests that it is a stage-specific marker for cerebellar neuronal development.

Adult↗
PubMed1988

Bone marrow transplantation for poor prognosis neuroblastoma.

These studies suggest that intensive chemoradiotherapy (eg., VAMP-TBI), if given relatively soon after diagnosis and before development of progressive disease, improves long-term survival for patients with advanced neuroblastoma. Although this particular therapy is not useful for those who already have developed progressive disease, other intensive regimens may warrant testing in this latter group of patients. Our current study is testing aggressive induction chemotherapy, ex vivo purging of autologous marrow, and VAMP-TBI followed by BMT. Because of the increasing risk of progressive disease with time after diagnosis, we recommend beginning the BMT phase by 20 weeks after diagnosis. This should result in 85% of newly diagnosed patients entering the BMT phase without progressive disease; and, with fewer toxic deaths, 90% should survive the BMT phase. Thus, approximately 70% of patients could be disease-free survivors 8-9 months after diagnosis. Because a significant number of patients still develop progressive disease during induction or after BMT, efforts are being made to improve induction and pretransplant therapies and to identify prognostic factors. If modifications of the current regimens do not decrease the rate of progressive disease, it may be necessary to develop additional or different therapy for patients identified to be at high risk. Hopefully, new strategies will further increase the percentage of patients with tumor-free survival.

Bone Marrow Transplantation↗
PubMed1987

Delayed surgery and bone marrow transplantation for widespread neuroblastoma.

From 1983 to 1986, 21 patients with poor prognosis neuroblastoma were treated with bone marrow transplantation. This regimen included induction chemotherapy, delayed surgical resection, local irradiation, and intensive chemoradiotherapy followed by infusion of allogeneic or autologous marrow. This therapeutic approach resulted in a 57% long-term survival rate (follow-up: 14-48 months), which appears to be approximately three times superior to conventional chemotherapy in a comparable group of children. In addition, complete resection was possible in 11 of 17 patients operated on after induction therapy. Recurrence in the primary site after bone marrow transplantation occurred in only one of 18 evaluable patients. Thus, this approach almost always eradicates primary tumor in patients with neuroblastoma with advanced disease.

Adolescent↗
PubMed1984

Gender and pre-atherosclerotic lesions. Effects on prevalence in human abdominal aortas.

Gross and microscopic examination of equivalent segments of abdominal aortas obtained at autopsy from 39 male patients aged 10 to 30 years (mean, 20.5 years) and 37 female patients aged 9 to 30 years (mean, 20.9 years) revealed no significant difference in the prevalence of aortic pre-atherosclerotic lesions in male v female patients. The prevalence of fatty streaks and early and late fibromusculoelastic lesions did not change significantly with increasing age, suggesting that in the abdominal aorta, the majority of precursor lesions for atherosclerosis are already present by 15 years of age. These findings suggest that the reduced severity of atherosclerosis in female patients is not due to the presence of smaller numbers (or extent) of precursor lesions, but rather to slower progression of these lesions in female patients.

Adolescent↗