Biomedical subjects
Publications and source records attributed to M Musset.
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RFCNU or (chloro-2-ethyl)-l-(ribofuranosyl-isopropylidene-2', 3' paranitrobenzoate-5')-3 nitrosourea, a new synthetic nitrosourea derivative, which has been shown to have, in mice, among all nitrosourea derivatives tested, the longest maximallly efficient dose interval (MEDI) and which is not immunosuppressive at the smallest dose of MEDI, gave in a phase II trial on digestive tract tumours (at the dose of 400 mg/m2 per month determined by the phase I trial), 30% objective remissions among which 13% were greater than 50%.
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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.
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.
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.
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.
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In 143 patients with poorly differentiated lymphosarcoma, leukaemic conversion has been observed in 25. The cytological type was prolymphocytic or lymphoblastic or lymphoblastoid (immunoblastic ?). Twenty-five patients were treated with chemo-radiotherapy, followed by active immunotherapy as if they had primary acute lymphoid leukaemia. A complete remission was obtained in 11. Four are still in first complete remission after 4 1/2 years. Among 136 patients suffering from so-called "poorly differentiated reticulosarcoma", 17 became leukaemic. The cells are cytologically very dystrophic and unidentifiable. A remission was obtained in 7 patients but it was of short duration (median 1 1/2 months, longest 7 months).
We have studied 20 cases of haematosarcomas belonging to lymphosarcomas (T or B-cell markers, absence of the reticulosarcoma characters in sections, on smears, with conventional and scanning electron microscopy). Their cells which appear as large pyroninophilic cells on sections, as large very basophilic cells with blastic nuclei and often cytoplasmic vacuoles on smears, as having many polyribosomes and usually no ergastoplasm with conventional electron microscopy, and as large cells of the lymphocytic series with scanning electron microscopy resemble the cells which we described in adenitis in 1955 (9) and in the graft-versus-host-reaction in 1961 (6), which Gowans (15) showed resulted from lymphocyte transformation, and which Dameshek (10) called immunoblasts. Many of these cases of immunoblastic lymphosarcoma (ILS) identified on their cytohistological characteristics [also recognized by Lukes et al. (24, 25) and Lennert et al. (21, 22)], present aetiological, clinical and pronostic characters which let us suppose that it may be not only a cytological entity but also a cytoclinical entity : a) it affects males in 85% or the subjects; eight patients came from mediterranean countries outside France; two patients had a history of chronic rheumatoid manifestations; b) the disease was at stage IV at the first presentation in 10 patients out of 20; it was revealed by profound (mediastinal or abdominal) localizations in 60% of cases (12 out of 20); it presented a hypoglobulinaemia in eight out of 13 patients; in six out of the 15 patients treated before leukaemic conversion, the chemotherapy usually efficient in lymphosarcoma (LS) failed to induce remission. This type of LS has a poorer prognosis than other types of LS (median for all stages : eight months). It led to the death either after its conversion to leukaemia (nine out of 20 cases), or by vital organ (as brain or kidney) infiltrations.
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The authors would remind us that the classification of the hemato-sarcomas is at present being reorganized and that, lymphosarcomas are appearing more and more in the form of disseminated diseases sensitive to chemotherapy as well as radiotherapy. It is highly recommended that first a pre-therapeutic check be carried out in order to classify the disease into one of the five stages before deciding on the therapy. The authors report on the association of radiotherapy and chemotherapy and the role of each as used in their treatment of the disease, at present.
The lipid-associated sialic acid (LASA) level in serum was increased in 663 out of 794 patients (83.5%) of which 55.1% were CEA negative. There were 16.5% LASA (possibly false) negative, CEA positive patients. There were 24.1% false positives in 116 patients without malignant tumors. In manifest prostatic carcinoma 94.2% of the LASA values but only 36.5% of the prostatic acid phosphatase values were increased. Similarly, in breast and pulmonary carcinoma, LASA was more sensitive than CEA. In 499 patients with minimal residual disease, 203 (41.5%) were LASA-negative, of which 180 were CEA-negative. Out of 180 LASA positive patients, 70 have relapsed, as have 70 out of 219 patients with increases in both LASA and CEA. The sensitivity of LASA (87%) in lymphoma was higher than that of the erythrocyte sedimentation rate (53.3%), of C-reactive protein (51.2%), serum copper (64.7%) and of six other markers.
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A study of 200 patients with breast cancer at different stages was carried out. Proliferating mammary cells in bone marrow were detected using a double-staining method with monoclonal antibodies. Mammary cells were visualized with antibodies raised against human breast tissue or carcinoma. DNA-synthetising cells (S-phase) were detected on the same slide, using the monoclonal antibody antibromodeoxyuridine (BrdU), after cell incubation with BrdU. Mammary cells could be detected in the bone marrow of 60% of the studied cases. In 50% of the samples with such 'micrometastasis', a high labelling index of the carcinoma cells was found. The correlation between the presence of micrometastasis and the general prognosis at the stage of residual disease is discussed.