Increase in "Null" cells in acute lymphocytic leukaemia in remission on long-term immunotherapy.
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Biomedical subjects
Publications and source records attributed to G Mathé.
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Six systemic adjuvants: living bacillus Calmette-Guérin (BCG), hydrosoluble extracts from BCG and from Mycobacterium smegmatis, bacterial lipopolysaccharide, lentinan and levamisole, have been tested for their ability to induce macrophage activation in mice. The first four adjuvants mentioned increase phosphatase activity of peritoneal macrophages and make them nonspecifically cytotoxic for tumor cells in vitro. The intensity of these phenomena vary with route and time of administration. In contrast, lentinan and levamisole depress both these macrophage activities. Living BCG, extracts from BCG and from M. smegmatis, and the lipopolysaccharide increase the cytotoxic potential of normal macrophages in vitro, suggesting that these agents may exert a direct action on macrophages. Levamisole did not activate normal macrophages in vitro. The existence of a correlation between the capacity of adjuvants to stimulate macrophage tumoricidal activity and their efficiency in active cancer immunotherapy is discussed.
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Twenty patients with very severe bone marrow aplasia were treated with mismatched bone marrow transplants. Engraftment and transitory chimerism (from 2-10 months) not complicated by secondary disease occurred in 4 patients. Of these, 3 are still alive after 5 years, with a compensated hematologic status. Engraftment failed in 16 patients; only 1 of these is still alive after 5 years.
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42 patients suffering from terminal leukaemic lymphosarcoma were treated as acute lymphoid leukaemia patients. 26 entered apparently complete remission (CR). They were submitted to complementary cell reducing treatment comprising systemic and intrathecal chemotherapy and radiotherapy on the CNS and on the lymphosarcomatous masses that had been detected at the beginning of leukaemic conversion. Eight relapsed during this treatment and 18 were still in CR at the end of it: nine were submitted to active immunotherapy (BCG + C. granulosum + irradiated allogeneic leukaemic lymphosarcoma cells): five out of the nine have remained free of disease for between 13 to 66 months. Nine served as controls: all except two, who are still at the beginning of the trial, have already died from leukaemic manifestations.
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The i.v. administration of living BCG to (DBA/2 X C57Bl/6) Fl mice pushd quickly the quiescent stem cells of bone marrow into S phase of the cell cycle. This treatment can be used to shorten the intervals of hemopoietic restoration after administration of combination cytotoxic chemotherapy.
This work presents the results obtained on 24 patients with disseminated lymphosarcoma and reticulosarcoma (stage III and IV) with a cyclic combination chemotherapy which combines adriamycin, epipodophyllotoxin (VM 26), cyclophosphamide and prednisone. The complete remission rate is 58 p.cent of the patients who entered the trial, the response rate is 75 p.cent. Tolerance of the regimen is good in general from the hematological point of view.
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18 acute myeloid leukemia patients were submitted to a Phase II active immunotherapy trial. The median duration of complete remission (CRD) (60 weeks) and of survival after remission (SAR) (104 weeks) were longer than those for our historical control groups. However, the CRD and SAR curves were not broken to form a "cure expectancy" plateau, as was the case for acute lymphoid leukemia.
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The authors report a ten year study of active immunotherapy using BCG and irradiated allogeneic leukaemic cells in 200 patients. In acute lymphatic leukaemia, 57 out of 168 patients treated in this way remained in primary remission for 18 months to 10 years after active immunotherapy was begun, the relapse rate became low after 18 months and nil after 36 months. The results varied according to prognostic factors: the cytological type, active immunotherapy being above all effective in small cell (microlymphoblastic and prolymphocytic) types with a hope of cure in 50 to 60 p.cent of cases; malignant cellular volume; meningeal deposits. In microlymphoblastic forms the possibility of survival at the 5th year is greater than 90 p.cent. After relapse during active immunotherapy sensitivity to chemotherapy does not seem to be diminished. Trials of active immunotherapy in acute myeloid leukaemia are worthy of further pursuit. The results of active immunotherapy in leukaemic lymphosarcoma show that immunotherapy may be effective in preventing local recurrence, both of tumour as well as in the marrow. Four patients are in apparently complete remission for more than four years. On the basis of these results, trials of active immunotherapy for "residual disease" should be undertaken in the field of cancerology, going beyond the realm of leukaemias.