Biomedical subjects
Publications and source records attributed to G Mathé.
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18 patients with malignant gammapathies (16 with myeloma and 2 with Waldenström's disease) were treated with human fibroblastic Interferon (beta IF). This was administered i.v. 6 X 10(6) units weekly (7 patients) or 3 X 10(6) units twice weekly (11 patients). during at least 3 months if tolerated. Treatment was discontinued because of side effects in three patients. Reduction of the M component, by at least 25% from the initial value, was obtained in 3 patients. In one case the disappearance of a urinary Bence Jones protein was observed. In 4 cases, there was a significant reduction of bone marrow infiltration by plasma cells. In 5 cases, major alleviation or disappearance of bone pain was observed. Duration of treatment seemed to be an important factor for activity. Immune monitoring with currently available tests, mainly natural cytoxicity, yielded no correlation with therapeutic effect in these patients. This preliminary study demonstrates the effect of fibroblastic Interferon in myeloma. However, further studies are necessary to determine the population of patients most likely to benefit from treatment, the best modalities, possible special indications, dose schedules and duration of treatment. As it is not myelosuppressive it could be indicated in the frequent situation of advanced myeloma with bone marrow failure, contra-indicating combination chemotherapy.
Nine patients with chronic lymphoid leukemia (CLL) were treated with subcutaneous human (leukocyte) interferon a (IF a). In the first part of the study, 7 patients received intermittent 10 day courses, with free intervals of 10 to 15 days and with dose escalation in the same patient from cycle to cycle from 1.5 to 6 X 10(6) units daily, if tolerated. As we observed a decrease of peripheral lymphocytosis with low doses, and as high doses gave more side-effect in the second part of the study, 4 patients (including two who has previously received intermittent courses) were treated for three months or more at a dose of 1.5 X 10 units daily. Tumor mass reduction was seen in only three patients. However, a significant decrease in peripheral lymphocytosis was seen in 7 patients who were sustained in the continuous treatment group; with relapse at treatment discontinuation in one patient and despite continuation in another. Immune monitoring with currently available T, B, NK and macrophage tests, showed a good correlation between NK cell activity and clinical response, in this group of patients. Further studies are warranted to determine the best modalities of treatment, the population of patients likely to benefit from such treatment, the possible special respective indications of IF, and also the other treatments of CLL. One can already consider as a reasonable indication CLL presentations with myeloid insufficiency as IF is not myelotoxic, contrary to chemotherapy.
Antibodies directed against the common acute lymphoid leukemia antigen (CALLA) were obtained from 2 hybridomas: J5 (Schlossman, mice sensitized with patient ALL cells), and Vil-A1 (Knapp, sensitization with the Reh cell line). The percentage of lymphoid cells reacting with these 2 monoclonal antibodies were compared. Antibody dilution curves indicated that the dilutions used yielded maximum percentages of positive cells. The percentage of CALLA-positive cells with the J5 antibody was significantly (p less than 0.001) higher than that found with the Vil-A1 antibody in 16 non-neoplastic inflammatory tonsils and in 13 non-Hodgkin lymphoma and chronic lymphatic leukemia lymph-nodes (p less than 0.05). In contrast, the difference between CALLA positive cells with J5 and Vil-A1 was not significant (p greater than 0.5) in 19 acute lymphoid leukemias. The difference between the ALL-cells, presumably pre-B, and the B-cells from the non-ALL subjects was also statistically significant (p less than 0.01). The results suggest that the two hybridomas form antibodies against different CALLA epitopes. Vil-A1 seems somewhat more specific for ALL than J5.
Four mycobacterial extracts--two water soluble and two water insoluble--were tested for their immunostimulatory and antitumor activities: MER, the methanol extraction residue fraction of tubercle bacilli (insoluble); HIU I, an insoluble component of the membrane of whole cells of bacillus Calmette-Guérin (BCG); HIU II, a soluble component of BCG; AND Lederer's WSA, a soluble extract of Mycobacterium smegmatis. In a hemolytic plaque-forming cell assay, MER, HIU II and WSA showed immunostimulatory activity. However, only MER was active in the immunoprophylaxis of L1210 leukemia and of the solid Lewis tumor. The loss of antitumor activity does not seem to be related to water solubility, but appears rather to occur during purification.
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No correlation was found between in vivo delayed hypersensitivity responses in cancer patients and in vitro lymphocyte transformation by mitogens or antigens, even when the same antigen [purified protein derivative of tuberculin (PPD)] was used for both the in vivo and in vitro testing. However, there was a good correlation between the in vitro lymphocyte transformation tests with PPD and with the mitogens phytohemagglutinin and pokeweed mitogen.
Using ultrastructural analysis, we studied the effects of hyperthermic treatment of one case of human liver metastasis from colon carcinoma. The results indicate that the main hyperthermic response involves the neoplastic and the histiocytic cell population. The drastic decrease in metastatic cells was accompanied by the appearance of cell fragments and apoptotic bodies. Consequently, the histiocytic component (Kupffer cells) showed increased frequency, indicating an activated state. The data are consistent with a direct action of the heat on tumor cells with subsequent activation of Kupffer cells.