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Of 91 acute leukaemia patients treated with m-Amsa, 19 received intermittent doses, 23 received daily doses and 49 underwent courses with combined m-Amsa and cytosine arabinoside (Ara-C). Intermittent doses had minimal therapeutic activity and toxicity. Among the 23 patients given daily doses, complete remission was observed in 5/12 relapses of ALL and in 2/11 relapses of AML. When Ara-C (200 mg/m2 x 5 days) was administered concomitantly with m-Amsa (200 mg/m2 x 5 days or 120 mg/m2 x 7 days), 17 out of 37 patients with advanced relapses of ALL (13/25 children and 4/12 adults) went into complete remission. While high doses of m-Amsa alone were well tolerated, the combined treatment with high doses of both drugs resulted in severe gastro-intestinal toxicity. Cardiac disorders were observed in patients who had previously received high doses of anthracyclins; there were 5 cases of dysrhythmia and 1 case each of sudden death, ECG alterations and heart failure. In view of its indisputable activity, m-Amsa should be used at an earlier stage in the treatment of acute leukaemias.

This is a review of the progress achieved in the treatment of acute lymphoblastic leukaemia, based on a series of 1580 children treated in Prof. Jean Bernard's unit, Paris, from 1956 to 1976. The children are retrospectively divided into three prognostic classes and five therapeutic categories. The benefits obtained from successive additions to the therapeutic armentarium during that period are conspicuous in all classes and categories and particularly striking in children with poor initial prognosis. The role of each component of the therapeutic measures applied is discussed.

The distinctive features and prognosis of Hodgkin's disease with initial bone marrow involvement were studied in 53 patients. This form is characterized by clinical and biological signs of rapid evolution, diffuse lymphoid tissue involvement with enlarged liver and spleen, increased lymphocyte depletion and pancytopenia--the last named being rare in other forms. Sternberg cells were found in 80% of bone marrow biopsies, often associated which fibrosis, which always disappeared during remissions. Remission was obtained with multiple chemotherapy (chiefly MOPP) in 82% of the patients and was complet in 44%. Blood toxicity was severe in cases with myelofibrosis. Relapses occurred in 14 out of 39 patients and were either local and responsive to radiotherapy or diffuse and invariably lethal. They usually took place in those lymph nodes which were most affected initially. Additional radiotherapy and courses of MOPP reduce the risk of relapse. The long-term prognosis was similar to that of other visceral forms, with a survival rate leveling off at 83% after 6 years in patients in complete remission.

Eighty-five patients with nodular lymphoma diagnosed between 1968 and 1975 were followed up for long periods and were treated by either conventional methods (local radiotherapy and single drug chemotherapy) or by more intensive therapeutic regimens, such as initial combined M.O.P.P. therapy and maintenance treatment with chlorambucil with or without further courses of M.O.P.P. Long-term follow-ups have brought to light some interesting points concerning the prognosis. Dissemination of the disease and large-cell histological pattern were, as already known, unfavourable factors. Neither age nor sex, nor bone-marrow involvement seemed to have any influence. Obtaining complete remissions improved the prognosis, but intensifying the initial and maintenance treatments proved disappointing: the survival rate remained the same, and the incidence of drug induced leukaemias was high. Indeed, relapses appeared to be less responsive to treatment when the patient had initially received multiple chemotherapy. However, in view of the high death rate of the disease (one-third of the patients in this series died within the first 5 years), trying new therapeutic regimens in the hope of obtaining better results, as has been done in Hodgkin's disease, would be fully justified.

Amongst 1500 cases of acute lymphoblastic leukaemia, affecting both sexes, the authors noted 111 testicular recurrences and 2 ovarian recurrences, i.e. an incidence of 16 percent. Clinical diagnosis is easy and testicular needle biopsy was reserved for doubtful cases only. Amongst 12 lymphographies, only one showed lumbar node involvement. Testicular involvement may exist before, after or in association with a bone marrow or a meningeal relapse. In 47 cases the first signal recurrence was a testicular tumour. The majority of these recurrences occured during the first two years of the disease, but late recurrences affecting the gonads are possible. Mean survival after an isolated testicular recurrence was 14 months, identical with meningeal recurrences. General chemotherapy and local radiotherapy were in general followed by an in situ or contralateral recurrence. Bilateral irradiation at a dose of 2400 rads is the best local treatment. However, in the light of the frequency of bone marrow recurrences a short time after, intensification of general treatment is necessary.

Seventy-four patients with acute pure monoblastic leukaemia treated between 1970 and 1978 were studied retrospectively. The disease was usually hyperleucocytic and tumoral in character. It occurred with equal frequency in subjects of both sexes and at all ages, with peaks at the two extremes of life. Rubidazone gave a high percentage (75%) of complete remissions, but the prognosis remained sombre, with a mean survival time of 200 days. The incidence of meningeal relapses was reduced by prophylactic measures at central nervous system level, but gingival and cutaneous relapses were frequent. The possibility of bettering the present modest therapeutic results by more intensive chemotherapy is discussed.

Anthracyclines, such as daunorubicin (DNR), rubidazone (RBD) and adriamycin (ADR) are intercalating drugs used in cancer chemotherapy. They inhibit synthesis of DNA and RNA, break DNA and inhibit mitochondrial oxidative chain. Their antitumoral experimental activities depend upon type of drug, tumor and route of administration. After i.v. administration, the drug is present in all tissues except central nervous system. Its disappearance from the plasma is biphasic with a long terminal half life, justifying intermittent chemotherapy. Anthracyclines metabolism occurs mainly in liver micrososomes, and 90% metabolites are excreted in the bile. The main toxicity is cardiac, as a congestive heart failure which appears when a cumulated drug dose is overcome. In man only, a few derivatives have been studied, compounds with activity and no cardiotoxicity are still in research. Action of malignancies depends on type of derivative. We use DNR since 1967, it is a remarkable active drug in induction treatment of AML, it is the only active drug on acute promyelocytic leukemia, and it increases number of remissions in all of adult patients and severe forms of children ALL. Adriamycin (ADR) is active on solid tumors (osteosarcoma, breast and thyroid cancers) and lymphomas. With rubidazone (RBD) we obtain 2/3 of remissions in acute monoblastic leukemia, and it is easier to use than DNR and equally active on AML. RBD is also active on severe cases of lymphomas (lymphosarcomas and Hodgkin's disease). A new compound DEA 14 DNR seems interesting: experimental antitumor activity is high (compared to DNR, RBD and ADR) and it appears to possess activity on solid tumors in man.

We studied 120 aptients within the following condition: moderate bone marrow myeloblastosis (blast cells + promyelocytes less than or equal to 50 p. cent); quantitative and/or qualitative medullary insufficiency; preservation of maturation of the granulocytic line without a gap; WBC count less than 20 000/mm-3. Computer analysis pointed out the following results: 1. This group may be differenciated from the group of acute myeloblastic leukemias by: a) a predilection for subjects older than 60 in 73 p. cent of cases; b) male dominance in 70 p. cent of cases; c) a sharply defined improved prognosis with a median of survival of 15 months and with more than 30 p. cent of survivors for more than two years; d) death in 63 p. cent of teh cases is directly due to a complication of bone marrow insufficiency, and only in 14 p. cent of the cases is related to blastic invasion; e) a complete absence of favourable response to intensive chemotherapy. 2. There are five initial prognostic parameters which are of statistical significance: a) the hemoglobin level; b) the sedimentation rate; c) the platelet count, the level of bone marrow cellularity, and age. 3. Multidimensional analysis makes it appear that the whole population obeys a unidimensional phenomenon and depends on a common "biological axis" constituted by the five prognostic factors which are inter-related. 4. The disease nevertheless may be subdivided into three subgroups; a) High inflammatory hypoplastic forms are a very high risk group; b) The group of slowly invasive acute leukemias in young subjects is a bad or moderately poor risk group; c) The forms with a purely qualitative disorder of myelopoiesis with very low evolutive potential. These observations point to: a) The concept of OBL as an entity of a distinctive type including the preleukemic syndrome, the myelo-monocytic leukemias, and the smoldering leukemias; b) The concept of a unique and basic bone marrow disorder which embraces the OBL and the common acute myeloblastic leukemia.

224 patients with stage III and IV Hodgkin's disease (H.D.) have been treated by 6 monthly MOPP courses. 190 patients achieved remission and among them there were 109 complete remissions (C.R.) . All patients received vinblastin maintenance combined with "reinduction" courses of MOPP (68 patients) or irradiation (57 patients). At ten years, remission curves are "on plateau" at 72% for those patients who achieved C.R. at 48% for those who had partial remission, and for all patients the ten years survival rate is 53%. The parameters which influence C.R. achievement are age, fever, histology, but the best predictive parameter seems to be lymphogram: diffuse involvement and aspects of cystic storage pattern as seen in "non Hodgkin lymphoma" heralding an unfavorable prognosis. The lymphogram picture should thus be included as parameter of initial classification and treatment active in "non Hodgkin lymphoma" such as Vincristine - Cytoxan - Prednisone - Adriamicin should be tried in these high risk patients.

In a retrospective study covering the years 1963-1976 and involving 1 094 patients, 33 solid tumours were found to have occurred in 31 patients previously treated for Hodgkin's disease. The mean actuarial risk at 10 years of developing a second solid tumour is estimated at 5.4%, but the incidence varies according to the treatment applied, being 10.9% in patients under combined chemotherapy and 1.8% in patients under single-agent chemotherapy (p less than 0,04). This would confirm the role of chemotherapy in the development of second solid tumours, the course of which does not seem to differ from that of indentical primary tumours. The overall risk of having secondary solid tumours after treatment for Hodgkin's disease is 2.4 times higher than in normal control population (p less than 0.01).