[Therapeutic trial of the sequential radiotherapy-chemotherapy association in the treatment of stages I and II of Hodgkin's disease. Preliminary results in Villejuif].
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Biomedical subjects
Publications and source records attributed to M Hayat.
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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.
The analysis of three subsequent randomized trials carried out within the frame of the European Organization for Research on Cancer (E.O.R.T.C.) enables to define a strategy for the staging and the treatment of early stages of Hodgkin's disease. Several prognostic factors were identified by multivariate analyses: 1) erythrocyte sedimentation rate, which has a greater impact on relapse-free survival than systemic symptoms but which can be combined with them; the combination of the two is a more powerful prognostic indicator than ESR alone; 2) the number of involved lymphatic areas: patients with one or two lymphatic areas involved (CS I and II2) have a better outcome than stage II patients with 3 or more areas involved (CS II3). Patients with favorable prognostic indicators are submitted to staging laparotomy because for them spleen involvement has a pejorative impact. For patients with unfavorable indicators, the spleen involvement has little prognostic significance and therefore those patients who need, anyway, an aggressive treatment do not undergo staging laparotomy. Patients with favorable prognostic indicators and negative staging laparotomy can be treated by radiotherapy alone, patients with positive laparotomy or patients with unfavorable prognostic indicators are treated by combination of multiple chemotherapy and radiotherapy.
Transgenic common carp, Cyprinus carpio, possessing the long terminal repeat (LTR) sequence of avian Rous sarcoma virus (RSV) fused to the rainbow trout (rt) growth hormone (GH1) complementary DNA (cDNA) were produced by microinjection. Initial studies showed that the transgenic common carp transmitted the foreign DNA to a significant fraction of their progeny in three of four crosses of transgenic males with control females. These progeny grew 20 to 40% faster than their nontransgenic full siblings. In this study, additional experiments were conducted to evaluate inheritance and expression of the foreign GH gene in transgenic common carp, and the growth performance of these transgenic fish. Four P1 (parental generation produced by microinjection) x nontransgenic controls, four P1 x P1, and one P1 x F1 matings of transgenic carp containing RSVLTR-rtGH1 cDNA were made. The percentages of transgenic progeny resulting from these matings were: 0, 32, 42, 100 (4 progeny only), 21, 21, 31, 30, and 23%, respectively. All crosses except 1 siblot (control x P1) exhibited progeny ratios below the expected 50 or 75% transgenic. These results indicate that most of these transgenic P1 had the foreign gene in their germ line but were mosaics, and at least one transgenic individual did not have the RSVLTR-rtGH1 cDNA in the gonadal tissue. Both P1 and F1 transgenic fish produce trout growth hormone mRNA and polypeptide as determined by reverse transcription polymerase chain reaction amplification, RNA dot-blot hybridization, and radio-immunobinding assay. Growth response by families of F1 transgenic fish to the addition of rtGH1 cDNA varied widely.(ABSTRACT TRUNCATED AT 250 WORDS)
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