Search PubMed⌕ Search

Biomedical subjects

L Schwarzenberg

Publications and source records attributed to L Schwarzenberg.

At least 37 records · Page 2Linked to original sources

[Treatment of leukemias and lymphomas by interferons: II. Phase II of the trial treatment of chronic lymphoid leukemia by human interferon alpha+].

Nine patients with chronic lymphoid leukemia (CLL) were treated with subcutaneous human (leukocyte) interferon alpha (IF alpha). In the first part of the study, 7 patients received intermittent 10 day courses, with free intervals of 10 to 15 days and with a rising dose in the same patient from cycle to cycle, if tolerance permits, from 1.5 to 6 X 10(6) units daily. 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 had previously received intermittent courses) were treated for three months or more at a dose of 1.5 X 10(6) units daily. Tumor mass reduction was seen in only three patients, but significant decrease in peripheral lymphocytosis was seen in 7 patients 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, in this population of patients, a very good correlation between NK cell activity and clinical response. Further studies are warranted to determine the best modalities of treatment as well as the population of patients likely to benefit from it, and the possible special respective indications of IF, and of 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.

Drug Evaluation↗

Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment.

Vitamin A and its derivatives, so-called retinoids, can prevent squamous metaplasia induced not only by vitamin A deficiency but also by carcinogenic hydrocarbons. An aromatic retinoid, such as ET1, has been shown to prevent chemically induced papillomas in mice and to amplify certain immunologic reactions. Heavy smokers, 106 volunteers, were submitted to fibrobronchoscopy with bronchial biopsies. An index of metaplasia (IM) was calculated on the basis of microscopical examination of a total of 9,633 sections of 1,010 biopsies. Despite the subjectivity of the estimates of cigarette consumption, this was significantly (P less than 0.02) and positively correlated to the IM. Eighty-five percent of the women had a low IM as compared to only 42% of the men (P less than 0.01), although there was no significant difference in the reported cigarette consumption. Fifty-two subjects had an IM greater than 15% and were given 25 mg ET1 orally daily for 6 months. The bronchoscopy was repeated in 30 patients following completion of the 6-month treatment. The IM was significantly (P less than 0.01) reduced after treatment.

Adult↗

Vindesine: a new vinca alkaloid.

Vindesine (VDS) is an analogue of the vinca alkaloids. Its spectrum of antitumoral activity is similar to that of vincristine (VCR), but with milder experimental neurotoxicity, and it inhibits the polymerization of tubulin. Its terminal half-life is 24 h and its plasma clearance is intermediate between those of vinblastine (VLB) and VCR. The maximal tolerated dose is 4-5 mg/m2/week, the dose-limiting toxicity being myelosuppression (nadir by days 7-8 and recovery by days 11-13). It has already been demonstrated as efficient in childhood acute lymphoid leukemia (ALL), non-Hodgkin's lymphoma, blastic crisis of chronic myeloid leukemia, and esophageal carcinoma. It has also shown activity in Hodgkin's disease, breast and germ cell carcinomas, and melanoma. Intolerance is mainly neurologic, with paresthesias, without motor impairment, or hematologic, with leukopenia, and sometimes alopecia, asthenia, and muscle pains. The results are better if the patients have not been treated previously; continuous infusion could be of interest and there appears to be no cross-resistance with its parent VCR, as documented in ALL.

Animals↗

Phase-II trial with vindesine for regression induction in patients with leukemias and hematosarcomas.

Vindesine (VDS) has been submitted to a phase-II trial, the results of which were assessed in terms of regression induction. VDS was given weekly IV in doses of 2 mg/m2 on two consecutive days to 59 patients, 55 of whom were evaluable. A high proportion of complete (36%) and over 50% partial regressions were obtained in acute lymphoid leukemias (ALL) (overall response 63%) whatever the perceptible phase, in blastic crisis of chronic myeloid luekemia (55%), and some responses were recorded in lymphosarcoma (40%). No effect has so far been seen in acute myeloid keukemia or in Hodgkin's disease. Malignant neoplasms of the immunoblastic type seem to be particularly sensitive to VDS. Continuous 48 h IV infusion can induce a remission where an IV push administration of the same dose has failed. One remarkable characteristic of VDS is the apparent absence of cross-resistance with VCR: in acute leukemic forms, 55% of patients who failed to obtain remission induction after three weekly injections of VCR (used in combination chemotherapy) achieved a complete or partial remission with VDS. The toxicity was mainly neurologic (paralytic ileus, constipation, paresthesias, loss of reflexes) and hematologic (leukopenia and thrombopenia), and was not more significant than with the other agents: four patients died of infection or hemorrhage.

Acute Disease↗

Bone marrow transplantation (1958-1978) : conditioning and graft-versus-host disease, indications in aplasias and leukemias.

Bone marrow transplantation (BMT), which stimulated great hope for treatment of aplasias and leukemias in 1958 following our first success in grafting this tissue, is, after a long period of study and development, experiencing renewed interest since it is now possible to obtain, in case of transplantation with genotypically matched sibling donors, 70% long survival (cures ?) in aplasia (under the condition that the recipient is not sensitized by previous transfusions) and in leukemia (under the condition that the recipient is transplanted in a period of remission and is not sensitized by transfusions). When the patient does not possess any genotypically matched donor, a trial of incompatible bone marrow transplantation after conditioning with antilymphocyte serum is reasonable, since we have obtained good, although unexplained, results with this method, which should be pursued. In any case, these transplants must be done in intensive care units in hemato-oncology departments.

Anemia, Aplastic↗

[Leukaemias and lymphomas treatment by vindesine. Result of a phase II trial in terms of remission induction (author's transl)].

Vindesine is a derivative of vinblastine and of vincristine. A high proportion of remissions were obtained in acute lymphoid leukaemia (6 complete and 1 incomplete remissions in 15 patients), in blastic crisis of chronic myeloid leukaemia, and a few responses have been registered in lymphosarcoma and Hodgkin's disease. Permanent 48 h i.v. infusion may include a remission where i.v. pusch of the same dose has failed. The most remarkable characteristic of vindesine is the absence of cross-resistance with vincristine as documented in acute lymphoid leukaemia.

Adolescent↗

Preliminary results of chemoradiotherapy followed (or not ) by active immunotherapy of stage III and IV lymphosarcoma and reticulosarcoma: correlation of the results with WHO categorization.

One hundred and one patients with advanced (stage III and IV) LS and RS at the first presentation of the disease or on relapse were treated with a regimen combining initial chemotherapy, complementary radiotherapy on "icebergs," supplementary chemotherapy, and finally, active immunotherapy. The overall complete remission rate was about 79% for LS and 73% for RS. About 50% of the patients were still in remission for both diseases after 2 years; 60% with LS were still alive after 2 years and 44% with Rs. This study shows the useful prognostic value of the WHO classification for LS and RS: the prognosis of prolymphocytic (centrofollicular) LS is far better than that of the lymphoblastic type, which is itself better than that of the very poor prognostic immunoblastic type. The prognosis of RS is intermediate between that of the best prognostic type and that of the poorest prognostic type of LS.

Adolescent↗

Preliminary results of chemo-radiotherapy followed or not by active immunotherapy of stage III and IV lymphosarcoma and reticulosarcoma. Correlation of the results with WHO categorisation.

We treated 101 patients with advanced (stage III and IV) lymphosarcoma and reticulosarcoma at first presentation of the disease or in relapse according to a protocol combining initial chemotherapy, complementary radiotherapy on icebergs, supplementary chemotherapy, and, finally, active immunotherapy. The overall complete remission rate was about 79% for lymphosarcoma and 73% for reticulosarcoma. About 50% of the patients were still in remission in each of the two diseases at 2 years; 60% of lymphosarcoma and 44% of reticulosarcoma patients achieved 2-year survival. This study shows the prognostic value of the WHO classification for lymphosarcoma and reticulosarcoma: the prognosis of prolymphocytic (centrofollicular) lymphosarcoma is far better than that of the lymphoblastic type, which is in turn better than that of the very poor prognosis of the immunoblastic type. The prognosis of reticulosarcoma is intermediate between that of the best-prognosis and that of the poorest-prognosis type of lymphosarcoma.

Adolescent↗

Preliminary results of a phase II trial of aclacinomycin in acute leukaemia and lymphosarcoma. An oncostatic anthracyclin that is rarely cardiotoxic and induces no alopecia.

A phase II trial of which preliminary results are available for 22 patients indicates that aclacinomycin applied in a continuous modality induced complete and partial remission in four of nine patients with acute lymphoid leukaemia that was resistant to all previously available drugs, and in four of eight patients with stage V lymphosarcoma (leukaemic). Bone-marrow toxicity was the major side-effect. Only one patient of 20 suffered from cardiac toxicity; no one had alopoecia. This very low incidence of myocardial lesions and the absence of hair loss had been predicted, respectively, by our electron microscope study of the myocardium and the light electron microscope study of the skin of golden hamsters [7], a test that detects frequent severe myocardium and skin toxicities for adriamycin and some anthracyclin analogues such as detorubicin, which was found to be toxic in a high percentage of patients in a clinical trial conducted by the E.O.R.T.C. Clinical Screening Group [8].

Acute Disease↗

Pharmacologic factors and manipulation of immunity systemic adjuvants in cancer therapy.

Because of the experimental and clinical studies which have been extensively conducted with bacillus Calmette-Guérin (BCG) as a systemic adjuvant in cancer immunotherapy, we have analyzed the main factors and conditions which determine its beneficial action and have underlined some of these (eg, the dose factor which controls the amplification of suppressor cells which is probably responsible for failures and even the possible tumor-enhancing effect of immunotherapy). Knowing those factors and conditions, we have been able to establish a systematic immunopharmacologic study of systemic immunity adjuvants, which has resulted in the discovery of agents whose actions are more rapid than that of BCG on one or a few populations of cells involved in immunity and which, unlike BCG, do not induce suppressor cell amplification. This amplification may explain the difference in the results obtained with this mycobacterium in various clinical immunotherapy trials in which it was applied differently. It is proposed to combine these mono- or pauc-functional adjuvants in order to try to obtain all of the beneficial effects of BCG without the amplification of suppressor cells.

Adjuvants, Immunologic↗

Phase II clinical trial with vindesine for remission induction in acute leukemia, blastic crisis of chronic myeloid leukemia, lymphosarcoma, and hodgkin's disease: absence of cross-resistance with vincristine.

Vindesine, an analog of vinblastine and vincristine, has been submitted to a phase II trial, the results of which are judged in terms of remission induction. A high proportion of remissions were obtained in acute lymphoid leukemia and blastic crisis of chronic myeloid leukemia, and a few responses have been registered in lymphosarcoma and Hodgkin's disease. A continuous 48-hour iv infusion may induce a remission where an iv push of the same dose has failed. The most remarkable characteristic of vindesine is the absence of cross-resistance with vincristine as documented in acute lymphoid leukemia.

Acute Disease↗