[Rapid recovery and sustained remission of a thrombopenic thrombotic purpura treated with plasmapheresis and vincristine].
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Biomedical subjects
Publications and source records attributed to L Barbolla.
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Auto-immune haemolytic anaemia (AIHA) has been found in a case of alpha-interferon treatment. Serum antibody and eluate were positive in the absence of the drug. Although the patient recovered after the treatment was stopped, DAGT remained positive for at least 8 months. The mechanism proposed to explain why this drug induced AIHA is similar to that proposed for alpha-methyl-dopa. Drugs could alter the red cell membrane and impair the immune system. Such changes have been observed with alpha-interferon and were related with increased autoimmunity.
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A clinical trial of an immunotherapy which consisted of intratumoural injections of autologous lymphocytes with human lymphoblastoid interferon was evaluated in 31 patients with intracranial glioblastoma. Immunotherapy was performed after stereotactic biopsy or surgical resection. The treatment was tolerated well by all patients. Three patients showed positive response to immunotherapy as documented by transient regression or stabilization of the tumour size on computed tomography. Nevertheless, there is no significant difference in the survival time of the patients treated with immunotherapy and those not treated. We conclude that this immunotherapeutic regimen is not beneficial in patients with glioblastoma when used as single treatment after tumoural biopsy or resection.
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Seven glioblastomas were studied between 1 and 6 months after intratumoral injection of autologous lymphocytes and human lymphoblastoid interferon. Morphological study showed a great number of lymphocytes within the tumor tissue, and interactions between lymphocytes and glioblastoma cells, suggesting a killing phenomenon. These data support the potential usefulness of adoptive immunotherapy in patients with glioblastoma by means of intratumoral administration of activated lymphoid cells.
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Preliminary experience with a clinical trial of immunotherapy for glioblastoma, by means of intratumoural injection of autologous lymphocytes (AL) mixed with low doses of human lymphoblastoid interferon (HLI) is presented. In two of twelve patients, a transient reduction of tumoural volume was obtained. Morphological studies showed that injected lymphocytes remain within the tumour, and suggest tumoural lysis due to activity of natural killer (NK) cells. Clinically no significant prolongation of survival time could be achieved and, as in other series, patients with additional radiation therapy survived longer. But the morphological findings suggest that immunotherapy carrying NK-cells to contact with tumoural cells might be useful in some patients with glioblastoma. Actually no explanation can be given why only two of our cases responded positively. Regarding the otherwise poor prognosis it seems justified to continue these studies.
From June/82 through November/85 bone marrow transplant recipients in our Institution were given only trimethoprim-sulfamethoxazole as prophylaxis against interstitial pneumonia. In December/85 we began a program of administration of passive immunoprophylaxis with hyperimmune plasma or cytomegalovirus-specific gamma globulin and transfusion of seronegative blood products to all bone marrow transplant recipients whether they were seropositive or seronegative prior to transplant. Nine of 36 patients in the historical control group and 9 of 32 patients in the study group developed an interstitial pneumonia. Interstitial pneumonia, once established, was treated empirically. The 9 patients in the control group received trimethoprim-sulfamethoxazole +/- adenine arabinoside, acyclovir, amphotericin B and anti-bacterial antibiotics; all died. Post-mortem study was performed in 7 (4 CMV, 3 idiopathic). The 9 patients in the study group received high dose cytomegalovirus-specific gamma globulin + acyclovir or ganciclovir in addition to the above measures. Four were cured, one relapsed and responded to treatment again. Five died (1 CMV, 1 candida, 3 idiopathic). We conclude that the prophylactic measures, as applied at our Institution, were inefficient. By contrast, therapy with specific immunoglobulin + acyclovir or ganciclovir can control a high percentage of patients. We compare this experience with reports from other centers.
Another important aspect of these transplants is the possibility of assessing the variations in the activity of serum ABH transferases in receptors of organs with ABH typing different from theirs. The antigenicity of these enzymes has been proven, antitransferase antibodies being found in BMT with minor mismatch, A-group receptors of O-group bone-marrow, and in SOT with major mismatch, O-group receptors of B-group liver. The study of the properties of such antibodies is of great interest in the course of GVHD or HVGD, in either form of transplant, as well as in the knowledge of the biochemical and immunologic characteristics of these ABH enzymes.
The contribution of the bone marrow to plasma A- or B-transferase activities has been studied in patients who underwent incompatible bone marrow transplantation (BMT). As deduced from major incompatibility (group O recipient/A donor), the contribution of the marrow to these plasma activities was c. 5-10% of the total activity. In cases of minor incompatible transplants (A recipient/O donor), normal plasma activity was present in two patients, while no activity was found in a further two in whom a potent antitransferase was detected. The antibody inhibited both A- and B-transferase activities to a high titre. The patients in whom this antibody arose exhibited severe graft-versus-host disease.
The contribution of the liver to plasma ABO glycosyltransferase activity has been studied in a group O individual transplanted with a liver from a group B donor. The B transferase activity present in the post-transplantation plasma was negligible. However, a potent B transferase inhibitor, absent from the pretransplantation plasma, was present after transplantation. The inhibitor was present in the excluded fraction following Sephadex G-25 gel filtration, but was retained by a protein A-Sepharose column, suggesting that it was an IgG antibody. This inhibitor was also effective in reducing A transferase activity.
In part I of this report, the CSF circulatory dynamics of autologous leucocytes labelled with indium-111 and injected in the subarachnoid space, in patients operated on for glioblastoma, were studied. In the Part II, a series of 11 patients with recurrent glioblastoma was studied for evaluating the efficacy of intrathecal injection of autologous leucocytes. Six patients previously had radiotherapy. The results in Part I show that after intrathecal injection of autologous leucocytes, these cells follow throughout the subarachnoid space and pass to the systemic blood circulation, showing no evidence of colonization of the tumour or deposit in the tumoural region. The mean survival of the patients studied in Part II was 8 months. Those six patients who received radiotherapy had a mean survival of 11.4 months, and those five who received only intrathecal injection of autologous leucocytes after surgery, had a mean survival of 4 months. This results seem to demonstrate that immunotherapy, as used in this study, is ineffective in patients with glioblastoma.
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