F. de Vassal

NEW ANTIGENS IN HUMAN LEUKÆMIC CELLS, AND ANTIBODY IN THE SERUM OF LEUKÆMIC PATIENTS

Abstract 51 patients with leukaemia or lymphoma, were subjected, before treatment, to a search for serum antibodies against their own leukaemic cells. Four tests were used: cytotoxicity, immunofluorescence on living cells, complement fixation, and immune adherence. The results of these tests were compared with those of electron microscopy for the presence of virus-like particles. In 12 patients, at least one of these immunological tests was positive, whilst virus-like particles were found in only 5. In 4 other patients, particles were found when immunological tests were negative. There was no strict correlation between the results of the various immunological tests. The most sensitive test was immune adherence. These results suggest that there are new antigens on the human leukaemic cells and that possible active antibodies against these antigens are present in the serum of these patients. These findings should certainly encourage further work to be carried out in this field of investigation, which has tended, until now, to be considered as rather negative.

Attempts at Immunotherapy of 100 Acute Lymphoid Leukemia Patients: Some Factors Influencing Results

There is an extensive literature on experimental active immunoprevention of cancer, which is the stimulation of immune reactions before the establishment of the tumor. This stimulation can be specific, consisting of the administration of irradiated neo-plastic cells, which generally produces a moderate effect [10, 22] or it can be nonspecific, consisting of the application of one or several agents that we have called “systemic immunity adjuvants” (SIA) [13], the most widely used being BCG injected intravenously [2, 4, 21, 26]. A marked effect is generally achieved by a combination of both means. Though the agents are administered by different routes, the effect of combined administration is usually much greater than that of the adjuvant given alone, which is itself superior to that of the irradiated tumor cells (ITC) [21].

Adriamycin in the Treatment of Acute Leukemias

This paper describes the results of our clinical trial of adriamycin in the treatment of acute leukemias, done after the first results of Bonadonna et al. [1]. A trial of this drug in solid tumors is at present being made by the “clinical screening group” of the European Organisation for Research on the Treatment of cancer (E.O.R.T.C.).

REMISSION INDUCTION WITH POLY IC IN PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (PRELIMINARY RESULTS)

The oncostatic effect of polyinosinic-polycytidylic acid (poly IC) on several varieties of tumors has been reported previously (Levy et al., 1969) and we have observed its effect on Walker’s tumor. A number of clinical trials have been conducted (De Vita et al., 1970; Krakoff et al., 1970) but they merely confirmed tolerance to the product and did not yield therapeutical results. Although the mechanism of the oncostatic action exerted by polynucleotides on experimental tumors is not precisely defined, it is thought that it is probably multiple, for poly IC is cytotoxic (Braun, personal communication), is an inducer of interferon (Field et al., 1967), is an adjuvant of immunity, as reported by Braun et al. (1968), and as observed by us by studying its effect on the multiplication of cells capable of forming antibodies in mice immunized with sheep red blood cells (Hayat and Mathe, in preparation). From this last-mentioned type of study, we have deduced the hypothesis according to which poly IC could have an action on acute leukemia only when the number of tumor cells is not very high. In fact, we have shown (Mathe, 1968; Mathe et al., 1969) that the adjuvants of immunity in the animal exert a detectable oncostatic action only when the number of cancer cells is low.

Nonspecific Immune Responses in Hematosarcomas and Acute Leukemias

Non-specific immune responses in cancer patients have been explored in several studies of both cell-mediated and humoral immunity [1, 2, 3, 4, 5, 6]. Since 1968 we have been systematically studying non-specific immune responses in leukemia and hematosarcoma patients [7]. The results are presented below.

Preliminary Data on Acute Leukemia Treatment with ICRF 159

We have treated 10 patients with acute leukaemia, 7 lymphoblastic and 3 myeloblastic, with ICRF 159 or dioxopiperazine propane (Fig. 1). All these patients were resistant to all the drugs so far available. The daily doses were 300 mg/m2.

Combination of Adriamycine, VM 26, Cyclophosphamide & Prednisone (AVmCP) in Chemotherapy of Lympho & Reticulum Cell Sarcoma (Stages & Topographic Forms III & IV)

The treatment of lymphosarcoma and reticulosarcoma (LRS) has been influenced by two main factors : a) the development of new chemotherapy compounds (1), especially VM26 or demethyl depipodophyllotoxin thehylidene glucoside (objective result rate, 45 % — see refs. 2 and 3) and adriamycin (objective result rate; 50 to 60 % — refs. 4,5 and 6) ; both compounds are particularly effective in treating this type of disease. b) Improved knowledge of the course of the illness, which depends on its histocytological type and anatomical aspect (7). The latter was studied during the most complete possible topographical inventory, including clinical examination radiology, isotopic investigations and exploratory laparotomy (7) including microscope examination of several biopsy specimens (7). There has thus been a considerable decline in the number of Stage I or II LRS cases considered curable by radiotherapy, and a corresponding increase in the number of stage III and IV cases successively treated by maximal regression induction chemotherapy EORTC, sometimes completed by radiotherapy applied to certain “icebergs” in the event of large initial localized tumours (10) ; such radiotherapy may be followed by additional chemotherapy and also by immunotherapy similar to that applied to acute lymphoid leukemia ; this immunotherapy has had remarkable effects on Stage IV leukemic lymphoreticulosarcomas (11).

Methods and Strategy for the Treatment1 of Acute Lymphoblastic Leukemia

Acute lymphoblastic leukaemia (A. L. L.) is a malignant disease in which the proliferating cells are conventionally identified as “lymphoblasts”, cells that are theoretically the precursors of lymphocytes (see Mathe and SEman, 1963).