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Biomedical subjects

G Bonadonna

Publications and source records attributed to G Bonadonna.

430 records · Page 24Linked to original sources
PubMedDate not supplied

Immunotoxin mediated killing of clonable T-lymphocytes infiltrating an irreversibly rejected human renal allograft.

We isolated and treated in vitro with a novel CD5-specific saporin immunotoxin, referred to as OKT1-SAP, the cells infiltrating an irreversibly rejected renal allograft from a patient who rejected while on cyclosporine plus steroids and then failed to respond to multiple courses of high-dose steroids, intravenous OKT3 antibody, and local irradiation to the graft. We report here that under experimental conditions achievable in vivo the immunotoxin OKT1-SAP was capable of eliminating in vitro more than 95% of clonable T-lymphocytes infiltrating the rejected allograft of this patient despite their resistance to previous aggressive immunosuppression. To our knowledge, this is the first report of an immunotoxin-mediated suppression of the clonogenic growth of rejected renal allograft infiltrating T-lymphocytes.

Adult↗
PubMedDate not supplied

Detection of occult leukemic cells in the autologous bone marrow graft of a patient with T-cell acute lymphoblastic leukemia by a highly specific and sensitive assay.

A patient with T-cell acute lymphoblastic leukemia (T-ALL) in second remission was treated with high doses of chemotherapy and radiotherapy, followed by transplantation of autologous bone marrow purged ex-vivo with an anti-CD5-saporin immunotoxin (OKT1-SAP). Prior to transplantation the bone marrow graft had been considered in complete remission, as assessed by morphology and immunophenotyping. Twenty-two days after transplantation, the disease relapsed in the bone marrow with the same phenotype as at the onset. Retrospective analysis of the transplanted marrow cells by a recently developed high sensitivity and specificity assay (HSS assay), involving immunologic fractionation and T-cell receptor rearrangement analysis, revealed a graft contamination of approximately 0.5% malignant T-cells. This finding, together with the early post-transplant leukemic relapse, strongly suggests that the bone marrow was the source of the leukemic cells. The data are discussed for their implications on residual leukemia detection by gene rearrangement studies.

Adolescent↗
PubMedDate not supplied

Detection of bone marrow minimal disease in non-Hodgkin's lymphoma patients by gene rearrangement analysis.

Bone marrow aspirates from 13 patients with non-Hodgkin's lymphoma of B- and T-lineage were drawn during staging procedures and examined by a combined technique involving immune selection and gene rearrangement analysis with DNA probes specific for the heavy-chain immunoglobulin gene (JH) or T cell receptor gene (T beta and T gamma). Morphologic examination of bone marrow biopsies revealed involvement by lymphoma in one case and suspicious accumulation of blasts in another. Southern blot analysis of the samples showed the presence of a rearranged clonal band in two samples, including the morphologically involved marrow. Clonal rearrangements were not detected in the suspected marrow. Bone marrow relapses were not observed in any of these patients after a median follow-up of 20 months. Antigen receptor rearrangements are tumor-specific markers which may increase the sensitivity and the specificity of morphologic examination, and may be useful in the proper staging and follow-up of lymphoma patients.

Bone Marrow↗
PubMedDate not supplied

Prognostic factors in Hodgkin's disease: implications for modern treatment (review).

This review outlines the major prognostic factors as derived from the analysis of recent prospective trials. Disease extent, systemic symptoms, age, sex, and achievement of complete remission lasting longer than 12 months following chemotherapy, as well as certain treatment-related complications (e.g. acute leukemia), constitute the major variables affecting survival. Bulky lymphoma and inadequate primary irradiation are factors which have influence on relapse-free but not necessarily on total survival. Recent reports provide no evidence that minimalizing treatment (except salvage treatment), will demonstrably reduce treatment-related complications. Optimal treatment, giving patients the best chance to enter first durable complete remission, still seems to represent the best strategic approach. However, in given patient subsets, the impact of various treatment strategies on the 5-, 10-, and 15-year results is now being balanced against delayed morbidity, such as organ damage and second malignancies, produced by the intensity of treatment or the prolonged delivery of certain drugs.

Hodgkin Disease↗
PubMedDate not supplied

Prognostic factors and response to treatment in non-Hodgkin's lymphomas (review).

This review outlines the major prognostic factors as derived from multivariate analysis of recent therapeutic studies in non-Hodgkin's lymphomas. Age at diagnosis (greater than or equal to 60 years vs less than or equal to 60 years), total number of involved sites, tumor bulk (mass size greater than or equal to 10 cm vs less than 10 cm), serum LDH (greater than or equal to 500 Units) and prompt achievement of complete remission following intensive combination regimens appear to be the most important variables predicting for cure in aggressive lymphomas. The clinical prognostic factors in follicular lymphomas were less extensively evaluated through Cox multiple regression analysis compared to large cell lymphomas. These factors include systemic symptoms, hepatosplenomegaly, anemia, as well as response to treatment. Treatment guidelines are provided in relation to high-risk and low-risk subsets rather than the classical stage assignment.

Cell Division↗
PubMedDate not supplied

Recent progress in multimodal therapy for resectable breast cancer.

Operable breast cancer with histologically positive axillary lymph nodes has been subjected to a number of prospective randomized trials with multimodal therapy in Milan since 1973. Available results indicate that the scientific and biological hypotheses that formed the basis of multimodal therapy were correct. In fact, five years after radical mastectomy, women who had received adjuvant chemotherapy with cyclophosphamide, Methotrexate and fluorouracil (CMF) showed significant improvement in relapse-free and total survival rates. The results were related to the level of drug administered as well as to the number of axillary nodes, but not to menopausal or estrogen receptor status. Future analyses will better define the optimal duration of CMF chemotherapy (12 vs. 6 cycles) as well as the efficacy of sequential noncross-resistant regimens.

Antineoplastic Agents↗
PubMedDate not supplied

Adjuvant chemotherapy for premenopausal breast cancer: a meta-analysis using quality-adjusted survival.

PURPOSE: Adjuvant chemotherapy for early breast cancer has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but the acute toxic effects of this treatment discourage some physicians from prescribing it. The purpose of this analysis was to determine whether the benefit of 6 months of adjuvant CMF (cyclophosphamide, methotrexate, fluorouracil) treatment outweighs its costs in terms of toxic effects. METHODS: A meta-analysis of quality-adjusted survival was performed based on data from 1229 patients, aged 49 years or younger, randomized in eight trials comparing CMF versus no adjuvant systemic therapy. The eight trials were included in the worldwide overview conducted by the Early Breast Cancer Trialists' Collaborative Group. The Q-TWiST method was used in a meta-analysis that provided treatment comparisons incorporating differences in quality of life associated with the amount of time patients spend with subjective toxic effects, after relapse, and without symptoms of relapse. RESULTS: Within 6 years of follow-up evaluation for patients with node-positive disease, the benefit in terms of increased relapse-free and overall survival balanced the costs in terms of acute toxic side effects. This was true even for the extreme case in which a zero value was assigned to all 6 months during which patients might receive adjuvant CMF chemotherapy. Within 10 years of follow-up evaluation, treated patients gained an average of 1.5 years of relapse-free survival time, almost 1 year of overall survival time, and 1 year of time without symptoms and toxicity. CONCLUSIONS: Adjuvant chemotherapy for younger women with node-positive breast cancer provided substantial amounts of quality-adjusted survival time, even after accounting for costs associated with toxic effects of the treatment. The Q-TWiST method represents a valuable tool for comparing treatments because it incorporates patients' perceptions of their quality of life for therapeutic decision-making.

Antineoplastic Combined Chemotherapy Protocols↗