[Autologous bone marrow transplants in Hodgkin's lymphoma. Analysis of cases from Genoa].
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Biomedical subjects
Publications and source records attributed to M Valbonesi.
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We have performed 24 cascade filtration treatments in 8 patients with hyperviscosity syndrome (2 cases), essential mixed cryoglobulinemia, post-hepatitic cryoglobulinemia, Sjogrens disease, rheumatoid vasculitis, Miller-Fisher syndrome and chronic dysimmune polyneuropathy. New cellulose diacetate filters were employed, giving a satisfactory performance. At 1.5 L plasma treatment, the rejection rate for macromolecular plasma components was close to 90%, whereas albumin recovery was close to 70%. Treatments were clinically effective, confirming that cascade filtration is an alternative to conventional plasma exchange in patients with IgM or immune complex mediated diseases.
In the treatment of Waldenstrom's macroglobulinemia (WM) and lipoprotein or immune complex mediated diseases, centrifugal and membrane plasma separation systems have been successfully employed over the past years. More recently, semiselective double filtration systems have been used in isolated cases. While it is hoped that cascade filtration (CF) will soon become a routine technique, a note of caution came from some investigators because of the lack of any evidence that CF does really deplete patients' plasma of known pathogenic macromolecules. The aim of this study was to test the efficacy of CF in the removal of IgM paraproteins in comparison with discontinuous flow centrifugation (DFC). Eight patients were treated by DFC and seven by CF; there were no significant differences between the two groups in terms of sex, age, clinical severity and IgM plasma concentration. After DFC or CF sessions, IgM concentration diminished by 50% and plasma viscosity by 60%, producing a comparable mean reduction in patients' clinical severity. Our in vivo results thus preliminarily answer the question whether CF is capable of removing known pathogenic macromolecules from patients' plasma, and the technique appears to warrant further investigations.
Data concerning 37 patients with inflammatory dysimmune polyneuropathy treated by discontinuous flow centrifugation, membrane plasma separation and cascade filtration are presented. Plasmapheresis was combined with immunosuppressants in patients with chronic or relapsing neuropathy (8 patients), cryoglobulinemic (6 patients) and paraneoplastic disease (2 patients), whereas 21 patients with acute Guillain-Barré syndrome (GBS) underwent exclusively plasmapheresis. Most patients were treated during the onset or progression of their disease and excellent or satisfactory clinical results were obtained in 18 patients with GBS, 6 with cryoglobulinemia, 2 with paraneoplastic disease and 4 with chronic relapsing polyneuropathy. Prior to therapy, 34 patients had high levels of immune complexes (CIC); this level was clearly reduced by plasmapheresis and clinical results correlated well with this removal. 3 patients with chronic dysimmune polyneuropathy, without any evidence of CIC, were completely unaffected by treatment. The possible role of CIC in demyelinating polyneuropathies is discussed on the basis of information given by cascade filtration treatment of 7 patients.
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Rebound after plasmapheresis is thought to be due to enhanced antibody and/or immune complex production. To prevent rebound a combination of steroids and immunosuppressive drugs has been used: lymphocytapheresis was employed in most patients, for not more than 10 sessions. 50 patients with myasthenia gravis, inflammatory myopathy, chronic dysimmune polyneuropathy and immune complex polyneuropathy have been treated and long-lasting benefits obtained in 35 patients. Rebound effects were observed only when cytotoxic drugs were not given or discontinued too soon. 8 patients who had been treated by plasmapheresis combined with steroids alone, after some recurrences of their disease, were switched to cytotoxic drugs, steroids and lymphocytapheresis combined with plasma exchange: in this group 7 patients eventually gained long lasting remissions. Our clinical experience strongly supports the hypothesis of a synergy between plasmapheresis and immuno-suppressive measures.
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Fifteen patients with symptomatic cryoglobulinaemia were subjected to apheretic treatment when acute renal insufficiency, glomerulonephritis, severe generalized vasculitis and polyneuropathy unresponsive to conventional therapy or complications due to steroids, such as vertebral collapse, peptic ulcer and steroid diabetes, had appeared. Treatment was performed by discontinuous flow centrifugation or cascade filtration: when discontinuous flow centrifugation was employed, a mixture of saline, gelatin and fresh frozen plasma was used for replacement. Cytotoxic drugs were administered to patients with lymphoma (4 patients) or chronic active hepatitis (5 patients) and also to patients suffering from essential mixed cryoglobulinaemia. Exchanges were organized into courses of 3 to 5 sessions over 5 to 10 days and employed as a supportive measure. No patient underwent long-term treatment. A complete resolution of kidney damage, skin involvement and neurologic signs was observed when treatment was started early in the course of the disease, whereas unequivocal but moderate improvement was obtained in the case of long-lasting symptoms such as polyneuropathy. Relapses were seen in most patients when cytotoxic drugs had been discontinued abruptly. In 8 patients the solubility of cryoglobulins was studied by a recently developed turbidimetric assay. Following treatment the solubility increased; when solubility decreased, 2 patients of this group had a relapse. On the basis of these preliminary observations it appears that the possibility of predicting relapsing disease or the need of continuing therapy can eventually be achieved.
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The rationale for and results of plasma exchange (PE) in the therapy of different immune-mediated neurological diseases such as myasthenia gravis, multiple sclerosis, acute and chronic-relapsing Guillain-Barré syndromes, polymyositis, dermatomyositis and amyotrophic lateral sclerosis are reviewed. Dialysis dementia and Refsum's disease, subacute sclerosing panencephalitis and schizophrenia are mentioned, too. If we exclude the treatment of acute Guillain-Barré syndrome, where PE alone appears to be sufficient to produce recovery or improvement, the combined use of immunosuppressive drugs and/or lymphocytapheresis is probably needed in the treatment of the other diseases. PE allows the disease to be controlled rapidly while long-term pharmacological control is established. An underlying theme in this review is the need of adequately controlled studies or at least of large case lists with exhaustive reports concerning both positive and negative results since a new perspective is needed for this topic. Nonetheless, a number of uncontrolled observations suggest that probably PE effectiveness in most immune-mediated neurological diseases could be proven if the requisite trials were performed.
We have developed a simple and rapid nephelometric test for the quantification of the osmotic fragility of red blood cells. 10 microliters of whole blood are mixed with hypotonic NaCl solutions under mechanical stirring while the hemolysis curve is continuously recorded for 1 min. In our preliminary studies, this test was reproducible, time-saving, easy to set up and to standardize. No false-positive or false-negative results have been recorded so far. Moreover, it seems that this test can differentiate heterozygous beta-thalassemic patients from patients with sideropenic anemia, which was hardly possible with previously proposed assays.
A new technique which allows lymphocytapheresis to be combined with cascade filtration (CF) is described in this paper. This therapeutical approach was applied for the treatment of patients affected by necrotizing vasculitis (1), inflammatory myopathies (5), Cryoglobulinemia (5), immune complex polyneuropathies (7), rheumatoid arthritis (3) and psoriasis (3 patients). Two cases of Waldenstrom's macroglobulinemia were also treated after the onset of the hyperviscosity syndrome. 78 procedures have been performed without any untoward effect. From a clinical point of view all patients had some improvement following treatment, thereby confirming not only the clinical safety of this therapeutical approach but also its effectiveness at least in the management of diseases which usually respond to plasma exchange treatment. Laboratory investigations showed that with CF it is possible to selectively remove IgM, immune complexes, fibrinogen, lipoproteins and high molecular weight plasma components, sparing most albumin and IgG globulins (85 and 71%, respectively).
A simple method for the study of kinetic solubility curves of cryoglobulins is presented. In its first application to the study of 21 patients with cryoglobulinemia, it was possible to ascertain that clinical condition roughly correlates with decreased solubility whereas no correlation is found with per cent cryocrit. In the group of patients we studied, 6 underwent plasma exchange treatment when glomerulonephritis, acute renal insufficiency, cerebritis and polyneuropathy appeared: in these patients, following 2 to 5 apheretic sessions, solubility increased showing a sort of correlation with clinical benefits determined by treatment. The preliminarity of this study is underlined.
A patient with severe Henoch-Schoenlein purpura was successfully treated by combined plasmapheresis and cyclophosphamide therapy. PE proved to be effective in the symptomatic treatment of the disease. Its possible role in the prevention and treatment of HS nephritis is suggested.
20 patients with myasthenia gravis (MG), refractory to anticholinesterase and steroid therapy, underwent plasma exchange therapy combined with immunosuppressive drugs and lymphocytapheresis. In all these patients an apparent clinical improvement was obtained since their first exchange session. During a follow-up of 8-18.5 months, a long-lasting benefit was achieved in 16 patients even though 6 of these had a single recurrence shortly after their first apheretic cycle. 3 patients who achieved substantial improvement of their symptoms during plasmapheresis showed recurrence of weakness after each apheretic course was stopped. However, their clinical response to therapy tended to improve with the following courses, which would be consistent with the effects of immunosuppression. This study strongly suggests that plasma exchange combined with immunosuppressive drugs and lymphocytapheresis can bring about dramatic and sustained improvement of MG and may alter its natural history.
58 patients were treated by discontinuous flow plasma exchange because of an immune complex (IC) disease. 41 patients who had a high level of circulating IC prior to plasmapheresis showed both clinical and immunochemical evidence of improvement with plasma exchange. Only 2 patients with a high level of IC did not improve after therapy: these patients suffered from multiple sclerosis and idiopathic thrombocytopenic purpura, respectively. Prior to PE therapy the level of circulating IC in 15 patients was within the normal range, when measured according to Manca et al. In this group none of the patients worsened after therapy, whereas 8 patients showed an objective improvement. The positive correlation between IC removal and clinical results suggests that patients with a high level of circulating IC are most likely to benefit from apheretic treatment.
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