The first Buenos Aires international workshop on cellular and molecular therapies.
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Biomedical subjects
Publications and source records attributed to B Koziner.
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Thirty-eight patients, including 14 with Hodgkin's disease, 9 with non-Hodgkin's lymphomas, 4 with multiple myeloma and 11 with solid tumors, were enrolled in our study. Between March 1995 and March 1997, 24 of these patients had been autografted with peripheral blood, and 14 had received peripheral blood autografts plus bone marrow. The study was a double-blind, prospectively randomized comparison of interferon gamma-1b (IFN-gamma), given subcutaneously at a dose of 50 microg/m(2) daily for 30 days to 18 of the 38 patients, vs. placebo (20 of 38). Administration started after 2 consecutive days of >0.5 x 10(9) neutrophils/l following autologous stem cell transplantation. At a mean follow-up time of 536 +/- 269 days, disease-free survival (DFS) for the IFN-gamma and placebo groups was 728 vs. 510 days, respectively (p < 0.0750 by the Generalized Wilcoxon/Peto-Prentice test). Overall survival (OS) time for the IFN-gamma and placebo groups was 830 vs. 755 days, respectively. Despite the limited number of patients included in this comparison, a trend for superior DFS was observed in the IFN-gamma-treated group, a finding which merits further study.
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A renewed interest in the transfusion of granulocytes for support of patients afflicted by severe and prolonged neutropenia has resulted from improved methods of mobilization and collection that provide cellular products superior in number and functions as compared with historical experiences of the 70's. In this review we discuss the clinical experience reported in the literature over the past three decades, the progress made in donor selection, the use of growth factors and mechanical apheresis. We comment on adverse effects, emphasize present indications and our own experience for the use of granulocyte transfusions. Hopefully, the progress made in this area will justify the consideration of granulocyte transfusions in the management of the severely neutropenic patient and provide proper documentation to avoid repeating the disappointment experienced in the previous two decades.
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We report the case of a 54 year old male with an original diagnosis of chronic myeloid leukemia (CML) who developed a nodal T cell blast crisis (BC) while he was in a complete hematological remission (CR). We describe the clinical presentation and the histological, immunophenotypic and molecular characterization of the lymph node blast cells. Our case, together with other rare similar reports in the literature, argue that a T cell nodal blast crisis of CML resembles the presentation of a T-cell non-Hodgkin's lymphoma.
An increasing body of literature has documented the usefulness of donor lymphocyte infusions in inducing remissions in patients relapsing post allogeneic hematopoietic progenitor cell transplantation. Efficacy was shown to depend on the disease entity; the best results have been reported in chronic myeloid leukemia in chronic phase, where the remission rate varied between 60 and 80%. In acute myeloid leukemia and myelodysplastic syndromes the remission rate ranged between 20 and 40% and in multiple myeloma the response rate was approximately 40%. In contrast, results have been poor in acute lymphoid leukemia with only 10-20% and even lower reported responses. Considering the efficacy of donor lymphocyte infusions in inducing responses in several hematologic neoplasias post allogeneic transplantation, as will be described in detail in this review, it is justified to anticipate an increasing role for this modality of treatment in relapsed non transplanted patients and as maintenance of the responses achieved with chemotherapy at conventional or high doses.
Multiple sclerosis (MS) is an autoimmune demyelinating disease exhibiting great clinical variability. For control of its primary and secondary progressive variants, treatment has met with limited success. In recent years, increasing experience has been gained with the administration of high dose chemotherapy supported by the autologous infusion of hematopoietic progenitor cells (HPC), in some instances depleted of T cells. The European and International Registry of Hematopoietic Cell Transplantation for Autoimmune Diseases include 43 MS patients. BEAM was the most frequently used conditioning therapy. Treatment related mortality was 7%. The actuarial disease free survival and the overall projected survival at 38 months were 85% and 90% respectively. The inclusion of an increasing number of MS patients into these treatment programs and the growing submission of cases to the Registries will provide useful information to determine if the initial enthusiasm generated by this approach for the control of primary and secondary progressive forms of MS is justified.
We report the clinical course of five adult patients with chronic Chagas' disease (Cd) who underwent BMT. Two patients with non-Hodgkin's lymphoma and one with ALL received an ABMT. Allogeneic BMT was performed in two patients with AML and CML respectively. One donor had chronic Cd. Samples of peripheral blood for parasite investigation by the Strout method, blood culture, and immunological studies by indirect immunofluorescent assay, ELISA and indirect hemagglutination tests were performed weekly from the start of chemotherapy until day +60 for ABMT and during the period of immunosuppression for allogeneic BMT. No prophylaxis was given to any of these patients. In only one ABMT patient were trypomastigotes detected early by blood culture without symptoms of reactivation. Benznidazole as preemptive treatment was administered at 5-8 mg/kg/daily for 30 days. Parasitemia was rapidly cleared and at the end of therapy xenodiagnosis was negative. The other Cd patients showed no evidence of relapse of parasitemia or signs and symptoms of reactivation. In brief, evidence of Cd should be sought in all BMT patients coming from endemic areas because parasitemia and reactivation are potential complications during the period of neutropenia and immunosuppression. The strategy used for early detection and treatment of parasitemia and reactivation was safe and effective.
OBJECTIVE: To evaluate in a multivariate analysis the prognostic factors associated with hematopoietic recovery and the supportive care requirements after autotransplant of progenitor cells (PC) from various sources: bone marrow (BMPC), BMPC & peripheral blood (PBPC), and PBPC alone. PATIENTS AND METHODS: A total of 570 patients with hematological malignancies and solid tumors underwent high-dose therapy followed by autotransplant. PBPC were obtained after mobilization with chemotherapy and/or cytokines. One-hundred five patients received BMPC, 217 received BMPC & PBPC and 248 PBPC alone; all of the patients received G-CSF or GM-CSF after infusion. RESULTS: In a multivariate analysis the recovery of neutrophils was adversely associated with low numbers of nucleated cells infused (P < 0.13), bone marrow progenitor cell source, and diagnosis of multiple myeloma and acute leukemia (P < 0.001). The factors that adversely affected platelet recovery were low number of nucleated cells and diagnosis of multiple myeloma and acute leukemia (P < 0.001). CONCLUSIONS: We conclude that BMPC adversely affect neutrophil recovery while low numbers of nucleated cells and diagnosis of multiple myeloma and acute leukemia adversely affect both neutrophil and platelet recovery.
We studied the effect of TPA, G-CSF, GM-CSF, conditioned medium from 5637 cells (CM5637) and IL-4 on U-937 cell line proliferation and differentiation. Flow cytometry analysis showed that the expression of the CD14 cell surface antigen, initially detected in 90% of the cells, decreased when the cells were cultured with either G-CSF, GM-CSF, CM5637, or IL-4. The CD11c expression only decreased by exposure to GM-CSF and IL-4. The cells also showed a decrease in alpha-naphthylesterase (alpha-NAE) activity and an increase in peroxidase (Px) activity in the GM-CSF supplemented cultures. Remarkable changes in cell morphology were also observed. IL-4 induced morphologic features resembling histiocytic-like cells positive for the expression of alpha-NAE and negative for Px. GM-CSF induced cells with pseudopods, negative for alpha-NAE expression and positive for Px. TPA effect on U-937 cells was similar to that observed with GM-CSF. No proliferative response was detected with any of the factors assayed. These results suggest that GM-CSF and IL-4 can promote distinct changes in the differentiative pathway of U-937 cells, as evidenced by the marked morphological, immunological and cytochemical changes observed in the cell cultures.
The early detection of clonogenic cells able to survive cytotoxic therapy and to initiate a neoplastic process, defined as Minimal Residual Disease (MRD), represents a major objective for the development of new and more sensitive diagnostic methods. The cloning of different chromosomal translocations along with the application of the Polymerase Chain Reaction (PCR) technique has allowed the characterization of various hematological disorders at the molecular level. This approach has led to the development of PCR based assays able to detect a minimum number of malignant cells with very high specificity. In the present paper we discuss the use of PCR and its value as a predictor for relapse in lymphomas, chronic myelogenous leukemia and acute promyelocytic leukemia, characterized by the t(14;18) t(9;22) and t(15;17) translocations, respectively.
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The administration of high dose chemotherapy and or radiotherapy with autologous hematopoietic rescue has become a treatment modality with increasing number of indications in a variety of malignant conditions. Improvements in the conditioning regimens and supportive measures used, as well as a more refined patient selection based on prognostic factors, have resulted in progressively better results. The availability of precursor cells from peripheral blood has allowed a faster restoration of hematopoiesis, decreasing the period and intensity of myelosuppression. The following revision gives an updated image of the accumulated experience with this mode of support in malignant lymphomas.
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To achieve a high percentage of durable complete remissions (CR) and prolonged survivals and reduce toxicity in patients with early-stage and intermediate-stage Hodgkin's disease, a randomized trial of four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa, bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT) was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5 years, the percentage of patients in CR was 90%, with freedom from progression of 89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of 59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and overall survival of 91% (P greater than 0.15). The median follow-up was 65 months (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2 relapses and 2 deaths. Short-term toxicity except for transient leukopenia was less for TBV and RT than for MOPP and RT. Good results are achievable with combined treatment without excessive toxicity.