Autologous bone marrow transplantation is a new technique in which some of the patient's bone marrow is removed and frozen to be reinjected later after heavy chemotherapy and/or total irradiation. Applied to solid tumours, this technique makes it possible to use tumoricidal agents to a degree never achieved before. In acute leukaemias bone marrow can be taken during complete remission, cleared in vitro of contaminating blast cells and reinjected after heavy chemotherapy and/or total irradiation have been given to consolidate the remission. The preliminary results of international trials indicate that this new approach to the treatment of acute leukaemias should substantially prolong the first complete remission and most probably increase the cure rate. The different methods used for in vitro depuration of leukaemic bone marrows (e.g. chemotherapy, monoclonal antibodies, immunotoxins) are described.

The renal toxicity of antitumoral drugs is an increasingly disturbing problem. These drugs are now prescribed in an ever wider variety of cases, and delayed renal reactions, previously unknown, are revealed by the longer survivals obtained. For a number of years, patients whose cancer had been cured have been placed under haemodialysis on account of drug-induced renal failure. The renal toxicity of cisplatinum, nitrosoureas and methotrexate is well-known, but mitomycin C is also capable of inducing permanent renal failure; the delayed toxicity of this drug explains that it has long been underestimated. This example emphasizes the need for close co-operation between oncologists, nephrologists and pharmacologists in order to determine, for each patient, the most effective treatment with the minimum of side effects.

Thirty-eight children, followed in the pediatric Department of Institut Gustave-Roussy, developed second malignant neoplasms. Intervals between the two neoplasms ranged from 1 to 26 years. The second neoplasms were defined as having a different histologic diagnosis than the first ones: osteosarcoma, fibrosarcoma, thyroid carcinoma, leukemia were the most frequent second neoplasms. The potential carcinogenic part of chemotherapy and radiotherapy is emphasized. In addition, some genetic susceptibility may enhance the carcinogenic effects of therapy. Nevertheless the incidence of second malignant neoplasms is low. Its estimation is discussed here.

Changes in mean corpuscular volume (MCV) were studied in cancer patients. Vitamin B12 or erythrocyte folate deficiencies were observed in only 9% of macrocytic patients (MCV greater than or equal to 100 fl). Bone marrow study in seven macrocytic patients with normal hemograms and normal levels of vitamin B12 and folic acid, on per os daily cyclophosphamide single agent therapy, showed myelodysplastic features. The highest MCV and MCV increases during therapy among 203 patients were observed in those cancers and cytotoxic therapies most commonly followed by secondary leukemia: Hodgkin's disease treated with MOPP and radiotherapy, and multiple myeloma and ovarian cancer treated with Melphalan. 21 patients who developed secondary leukemia had a higher MCV and a greater MCV increment than the control patients. Differences were significant in Hodgkin's disease. This preliminary report strongly supports monitoring MCV changes during cytotoxic therapy to attempt identification of patients at high risk of secondary leukemia.

A 12 year old boy with Burkitt's lymphoma developed severe hepatitis with hepatomegaly, subclinical jaundice, and a small rise in body temperature, associated with an important rise in SGPT and fall in prothrombin titres, 6 days after anticancer chemotherapy and 24 hours after halothane anaesthesia. Hepatitis A and B serology remained negative. This hepatic failure explained perhaps the unusually severe vincristine toxicity which gave rise to a polyneuritis with important sequelae. The association of halothane hepatitis with antimitotic drugs appeared particularly dangerous, and halothane should probably be avoided in all patients been given or about to be given anticancer chemotherapy.

This paper emphasizes the importance of occupational hygiene in the hospital. By taking into account the differences between hospital hygiene and industrial hygiene one realizes that these sciences are quite complementary. A few occupational stresses or hazards are described some of them being unspecific to the hospital and the other ones being specific i.e. they are not usually present in other industrial situations. Among these are anesthetic gases, ethylene oxide and cytostatic agents. Examples of results obtained during field surveys are given and briefly commented. The occupational hygienist is an important member of the team aiming at the protection of the workers' health in the hospital.

The anti-emetic action of alizapride was compared to that of metoclopramide in a strict double-blind study of 57 cases files derived from 21 patients treated with anti-mitotic chemotherapy. For each treatment, each patient received two ampoules before and after the chemotherapy. Each ampoule contained either 50 mg of alizapride or 10 mg of metoclopramide. There were 24 good or excellent results and 4 nil results with alizapride and 16 good or excellent results and 13 nil results with metoclopramide. The superiority of alizapride over metoclopramide was therefore established with statistical significance (0.05 greater than p greater than 0.02).

The aim of adjuvant chemotherapy is to cure micrometastatic disease and to prevent relapses after apparently complete surgical exeresis. It is almost always administered after initial surgical treatment, except for stage IA1 malignant epithelial tumours and stage I-II pur dysgerminomas. Chemotherapy combines anthracycline, an alkylating agent, a plant alkaloid and cis-platinum, for 4-8 months. After second-look laparotomy, if no more macro or microscopic tumor have been discovered, adjuvant chemotherapy does not seem necessary. However it is when all residual tumor has been excised or cyto- and/or histologic controls are positive. Optimal schedules are not yet perfectly defined. In some cases, a third look laparotomy should confirm the absence of tumor in order to stop treatment. Side effects (hematologic, gastrointestinal, neurologic, renal) are frequent. It is necessary to recognize patients able to benefit from chemotherapy and to define the least toxic treatment.

Medical, psychologic, socio-professional and economic side effects of adjuvant chemotherapy are frequent. Some of these are not easily recognized with accuracy. They influence directly the life of treated patients and perhaps later their medical future. They involve the quality of life for cancer patients, after initial curative treatments. Indications for adjuvant chemotherapy cannot be extended without comparative evaluation of their advantages and disadvantages. It is necessary to select patients with the highest probability of improvement in the duration and the quality of life and to give them so active but the least toxic treatments possible.

An induction chemotherapy, before any local treatment, allows to precise the chemosensitivity of the primary tumor. These data may help to improve indication and type of a further adjuvant chemotherapy. However there are many biological differences between different sites of the same tumor and along the time, without or after treatment. It is thus impossible to be sure that a chemotherapeutic regimen effective as first treatment on the primary will be equally active on micro-metastases some months later. Many questions in this field will be answered only by controlled studies and careful observations.

9-hydroxy-2-methyl-ellipticinium (HME) is an intercaling agent mainly potent in metastatic breast cancer. Its almost complete lack of bone marrow toxicity is of greatest value. However, among 385 patients 20 cases of renal failure were observed: renal failure is gradual, non reversible except in four cases with acute renal failure. Histological and ultrastructural studies, performed in 8 cases, showed exclusively proximal tubular lesions, without glomerular or interstitial lesions. We have evidence that there is a relation between the cumulative dose and the severity of the lesions. A prospective study was done in 30 patients. An increase in enzymuria, proteinuria and glycosuria was observed in most patients after HME infusion. HME is an efficient drug in the treatment of bone metastases of breast cancer. Renal function should be carefully monitored during HME administration.

The cardiotoxicity of the anthracyclines, of which doxorubicin is the leading drug, manifests itself in two ways: acutely, giving rise to temporary and usually benign phenomena, and chronically, giving rise to cardiac failure which is often irreversible. The risk of cardiomyopathy is related to the total dose of anthracycline administrated. The main risk factors are, age, previous cardiac disease and mediastinal radiotherapy. The prevention of cardiomyopathy is based on the respect of empirical guide lines (interruption of anthracyclines at "threshold" cumulative doses) and on methods of detection of infra-clinical disease. Myocardial angioscintigraphy which is easier to perform than myocardial biopsy and more sensitive and specific than echocardiography seems to be the investigation of choice. The main lines of research are aimed at improving our understanding of the mechanism of the cardiomyopathy, the institution of clinical trials to detect the first signs of toxicity of continuous infusions, the improvement of the standardisation and specificity of methods of detection, better definition of alarm thresholds and the development of new, less cardiotoxic, anthracyclines and cardioprotective agents.

Adjuvant antimitotic chemotherapy increases the survival rates of patients suffering from breast cancer with nodes involvement, but its effects on the immune status are still unclear. The immune status of these patients was studied from the general point of view and particularly from the antitumoral immunity. The most studies which have been made, indicated a such immunity was present, and proved it was more important when the tumor's invasiveness is limited without node involvement. From a general point of view, when an immunologic impairment is present in patients with breast cancer, it seems to have a poor prognosis. Many modulations of this immune status are determined by the treatment's modalities: surgery and radiotherapy have more or less local or general immunologic effects and in certain conditions, antimitotic chemotherapy is immunosuppressive, but it may also interfere as an immunoregulator with a good effect on antibody secreting cells or on suppressive cells. Several situations may be considered according to the tumor immunogenicity and the host immunologic competence. In these different cases, immunotherapy is not always indicated and when this one is, its specificity is still not sufficient. The recent results of specific or non specific immunotherapy trials performed after locoregional treatment or antimitotic chemotherapy are generally not significant and do not lead us to propose a modulation of immune status without controlled trials.

Results of a phase II clinical trial of vindesine sulfate in differentiated carcinoma of the upper respiratory and digestive tracts demonstrated good efficacy, with 6 objective responses in the 14 patients with interpretable reports several toxic reactions were observed, three patients developing polyneuritis of the upper and lower limbs after doses of 33 to 40 mg of DVA. Hematologic toxicity was moderate and regressive.