Autologous platelet collection and storage to support thrombocytopenia in patients undergoing high-dose chemotherapy and circulating progenitor cell transplantation for high-risk breast cancer.

OBJECTIVES: The use of circulating progenitor cell support following high-dose chemotherapy for malignancies decreases but does not entirely abolish platelet transfusion requirement. We investigated the feasibility of supporting the posttransplant thrombocytopenic phase exclusively with autologous platelets collected by apheresis and cryopreserved. METHODS: 25 patients underwent plateletpheresis during the platelet rebound occurring after high-dose cyclophosphamide. Autologous platelets were cryopreserved in 5% dimethylsulfoxide, thawed and transfused during the aplastic phase after the myeloablative regimen whenever clinically required. RESULTS: A single plateletpheresis was carried out in all patients, allowing the harvest of a platelet concentrate with a mean value of 7.7 x 10(11) platelets. No significant procedure- or transfusion-related side effects were recorded. Mean platelet recovery after freezing and thawing was 63% and the mean number of platelet reinfused was 4.8 x 10(11); 23 of 25 patients were fully supported with autologous platelets. CONCLUSION: Plateletpheresis performed in our selected group of patients was found to be a safe and effective procedure to collect large amounts of autologous platelets; the numbers obtained proved to be sufficient for the transfusion demand of almost all patients.

On the role of the acidic cluster Glu 92-94 of spinach ferredoxin I.

The role of the acidic cluster Glu 92-94 of spinach ferredoxin I in the interaction both with the photosystem I multisubunit complex and the ferredoxin-NADP+ reductase, either membrane-bound or purified, was studied by kinetic characterization of site-directed mutants. Three mutants of ferredoxin have been produced to evaluate the effects of elimination of one or two negative charges in the three specific positions of the acidic cluster. Kinetic characterization of the ferredoxin mutants E92A/E93A, E93A and E93A/E94A as electron carriers in the photosynthetic electron transport chain, allowed to establish that the two latter mutants were nearly indistinguishable from the wild-type protein in their ability to be photoreduced by photosystem I and as electron donor to the reductase in the NADP+ photoreduction with thylakoid membranes. The E92A/E93A ferredoxin mutant behaved very similarly to E92 mutants previously characterized. Thus, the elimination of the carboxyl groups adjacent to residue 92 did not further impaired ferredoxin I main function, i.e., as an electron carrier in NADP+ photoreduction. The two double mutants showed a reduced rate in the cross-linking of ferredoxin to the reductase promoted by a soluble carbodiimide, indicating an involvement of the acidic cluster in the formation of the active covalent complex between the two proteins.

Early-stage Hodgkin's disease: long-term results with radiotherapy alone or combined radiotherapy and chemotherapy.

BACKGROUND: Controversy still exists over the optimal management of early-stage Hodgkin's disease (HD); presentation features may have a different prognostic impact according to initial therapy, and long-term toxicity must be fully evaluated. PATIENTS AND METHODS: This study included 164 patients with stage IA-IIA HD treated with radiotherapy (RT) alone or combined radio- and chemotherapy (CT) according to presenting features and their attendant prognostic significance. The RT group included 88 patients with favorable prognostic features; the combined modality group included 76 patients with one or more unfavorable features. In the RT group, 85% of patients received extended-mantle or STNI; in the combined modality group, RT consisted of mantle- (49%), extended mantle- (37%), and involved-field irradiation (14%); CT consisted of 6 cycles of MOPP before 1984; 3 cycles of ABVD were substituted for MOPP thereafter. RESULTS: Complete remission was obtained in 94% and 99% of patients of the RT and combined modality groups, respectively. The 10-year actuarial relapse-free survival (RFS) in the RT group was 62% and was influenced by stage (p = 0.04) and histology (p = 0.01); in the combined modality group, RFS was 88% and was influenced by the presence of bulky disease. Overall survival and tumor mortality between the therapy groups were comparable. RT-related toxicity consisted of mediastinal fibrosis (8 cases), myelitis (3), hypothyroidism (2); other long-term events included 2 cases of acute leukemia in the combined MOPP and RT group. Altogether, 8 of 20 patients who died were in their first complete remission. CONCLUSIONS: In stage IA-IIA HD, the combined modality therapy reduced the risk of relapse compared to radiation alone; long-term toxicity of RT was not negligible and relapses could occur late.

Analysis of long-term results and prognostic factors among 138 patients with advanced Hodgkin's disease treated with the alternating MOPP/ABVD chemotherapy.

BACKGROUND: A prospective study was conducted to assess (a) the long-term results and toxicity of the alternating MOPP/ABVD regimen in advanced Hodgkin's disease; (b) the prognostic value of pretreatment variables and of drug dose intensity. PATIENTS AND METHODS: A total 138 consecutive patients with advanced Hodgkin's disease entered this study; patient selection included stages IIB (33% of total), IIIB (26%), IV (25%), and stages IIA-IIIA (16%) with bulky disease and pulmonary hilum involvement. The MOPP/ABVD program was delivered in an 8-month program; adjuvant radiotherapy on sites of bulky disease was delivered in 24 patients. RESULTS: Complete remission was obtained in 106 (77%) patients; significant factors for CR in univariate analysis were stage, symptoms, histology, and bone marrow involvement. The five-year relapse-free survival (RFS) was 83%; in a multivariate analysis, histology only correlated with RFS (p = 0.04). The five-year freedom from tumor mortality and overall survival (OS) were 79% and 67%, respectively. An adverse prognostic significance for OS was observed for B symptoms and bone marrow involvement. The median percentage of relative dose intensity (RDI) was as follows: Adriamycin 86, mechlorethamine 85, vincristine 73, vinblastine 84, bleomycin 79, procarbazine 74, dacarbazine 81. No significant association was found between RDI and clinical outcome. No severe pancytopenia or life-threatening complications occurred during therapy. CONCLUSIONS: Alternating MOPP and ABVD cured more than 65% of patients with advanced HD; acute and late toxicity were acceptable. Prognostic analysis defined subgroups with a lower chance of cure which may deserve a more intensive initial therapy.