J. L. Amiel

Bone Marrow Graft in Man after Conditioning by Antilymphocytic Serum

Allogeneic bone marrow grafts carried out after previous administration of antilymphocytic serum alone were attempted in 16 patients. Of these, six had acute myeloblastic leukaemia, four acute lymphoblastic leukaemia, and one a blast cell crisis in polycythaemia vera. Ten of these patients were in an overt phase of the disease and resistant to chemotherapy, while nine had complete agranulocytosis. In five of these patients erythrocyte and leucocyte antigenic markers demonstrated the establishment of the graft. One patient had thalassaemia major, and four others had aplasia of the bone marrow, in one case due to chloramphenicol poisoning and in another to virus hepatitis. The grafts were successful in the last two patients and transformed their clinical condition. No signs of early acute secondary disease were noted in any of the patients, either when the donor had been given antilymphocytic serum or when he was untreated. The grafts had no adoptive immunotherapeutic effect on the acute leukaemia. These observations have clearly shown that antilymphocytic serum has an immunosuppressive effect in man when it is used alone.

Two epipodophyllotoxin derivatives, VM 26 and VP 16213, in the treatment of leukemias, hematosarcomas, and lymphomas

The preliminary results obtained with VM 26 and VP 16213 (two semisynthetic derivatives from epipodophyllotoxin) on leukemias and hematosarcomas are described. These compounds are phase M dependent, myelostatic agents whose toxicity can be controlled by intermittent administration. VM 26 proved capable of inducing regression in Hodgkins disease, reticulosarcomas, and lymphosarcomas. Its most remarkable effect was the total regression of neoplastic pleural effusions by systemic administration. VP 16213 seemed to be effective on the same hematosarcomas, but less often. Its most striking action was its oncostatic effect in acute monocytoid leukemia and in the monocytoid component of acute myelomonocytoid leukemia.

Hydroxyurea, Leucopheresis, and Splenectomy in Chronic Myeloid Leukaemia at the Problastic Phase

Forty-three patients with chronic myeloid leukaemia have been treated with hydroxyurea in order to be subjected to leucopheresis for white cell transfusions. Hydroxyurea decreases leucocytosis when it is administered and the blood granulocyte number increases soon after the drug is stopped. The survival of the patients is not different from the survival of the patients treated with conventional chemotherapy (busulphan, mitobronitol) and it is superior to the survival of patients treated with external radiotherapy or with 32P. Half of the patients were subjected to splenectomy during first remission for a phase II trial. They were not randomized, but the distribution according to age was similar in the two groups. A slight difference appears in favour of splenectomy so far as survival is concerned, but there were three post-operative deaths out of 18 patients. We conclude that a phase II trial on the value of splenectomy is indicated ethically, but that the patients should be operated on and nursed in a microbiologically controlled environment.

TREATMENT OF ACUTE TOTAL-BODY IRRADIATION INJURY IN MAN

The treatment of total-body irradiation injury is essentially based on a very intensive symptomatic therapy (maintenance of patients in aseptic conditions, rational and not systematic use of antibiotics, platelet transfusions when the level of these cells is below 50,000); allogenic bonemarrow transfusion is indicated in case of failure of this symptomatic therapy, whether the dose of irradiation is 100% lethal or less. (auth)

1975 current results of the first 100 cytologically typed acute lymphoid leukemia submitted to BCG active immunotherapy

SummaryThe first 100 acute lymphoid (and undifferentiated) leukemias, (of which the smears at the first presentation of the disease are still available for typing), treated successively with remission induction chemotherapy, complementary cell-reducing chemoradiotherapy and then active immunotherapy with irradiated pooled allogeneic leukemic cells and fresh Pasteur Institute BCG applied on scarifications, have been reviewed, especially in connection with BCG application.Tolerance of BCG has been good. Its application had to be stopped due to a side effect (choroiditis) in only one patient. This toxic cost is negligible compared to that of so-called maintenance chemotherapy.No subject of our first control trial started in 1963 has relapsed between 3 and 13 years.In the overall group of the 100 patients studied, no relapse has been observed after 48 months, which is quite different to the observations of frequent relapses after that time in patients submitted to maintenance chemotherapy.Moreover, second remissions are obtained in 94% of the patients who relapsed early under immunotherapy, and their life expectancy after a second remission is as high as it is after the first remission.The median of survival is longer than 5 years.The action of active immunotherapy on the immune machinery has been followed by several assays, of which the increase of null cells (which include K-cells) may be the most interesting.Several prognostic factors have been demonstrated among which are sex, the volume of the neoplasia, meningeal localizations, and the cytological types. Age has no prognostic value in immunotherapy patients, contrary to maintenance chemotherapy patients. Also the cytological types behave differently under immunotherapy and under maintenance chemotherapy. The disease-free survival of more than 85% of the microlymphoblastic patients submitted to immunotherapy is not observed in J. Bernards patients submitted to maintenance chemotherapy, which suggests that this high cure rate is due to active immunotherapy. Hence, these prognostic factors are probably factors of sensitivity to active immunotherapy. A statistical computerized study has shown that there is a link between the cytological types and other prognostic factors and that they all depend on the cytological type.Hence, our present protocol is adapted to this immunotherapy sensitivity factor. It comprises a nonrisk preimmunotherapy chemotherapy for the microlymphoblastic type, and a longer and more intensive chemotherapy for less immunotherapy sensitive types.

Pathogen-free isolation unit — Three years' experience

The results obtained during the first three years of a pathogen-free isolation unit containing five beds have shown that this type of unit can reduce the risk of infection in patients treated with intensive chemotherapy or in those who have granulocytopenia from various causes. It is suggested that treatment of cancer which involves these risks should be carried out routinely in sterile isolation units, and that it is urgent to build many more and much larger units.

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.

Treatment of Blastic Crisis in Chronic Myelocytic Leukemia

The development of an acute leukaemic syndrome can perhaps be considered to be the usual evolution of chronic myeloid leukaemia. Its occurrence is feared and its prognosis is still very poor, despite recent advances in treatment. Twenty-nine patients have been studied, 14 males and 15 females, their ages were 16–71 years (median 40 years). The acute leukaemic syndrome appeared 3 weeks to 7 years after the apparent onset of chronic myeloid leukaemia (median 26 months).