[Prevention of hepatic metastases in ocular melanoma].
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Biomedical subjects
Publications and source records attributed to M F Auclerc.
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Chronic lymphatic leukemia (CLL) is a disease with a prognosis that has previously been difficult to assess. In recent years, this problem has largely been overcome by various classifications based on clinical and hematologic findings. This article presents the results of a study designed to show the value of lymphograms in assessing the prognosis. These results show that prognosis is associated with lymph node structure, as assessed by lymphography. Lymphography, as an investigation is superior to scanning or echography, since these give information merely on nodal size. It is proposed that lymphograms should be used for assessing the gravity of the disease and help in the choice of therapy.
About 80 per cent of patients with breast cancer ultimately die of metastatic disease in the following twenty years. Distant metastases are more important as cause of death than loco-regional relapses, it is why adjuvant chemotherapy is necessary, especially in young patients and in those with extensive disease. Initial chemotherapy preceding any locoregional treatment is justified on the basis that both surgery and anesthesia lead to immuno-depression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials of Nissen-Meyer, Bonadonna and Cooper. We have treated 145 patients, including 67 with inflammatory breast cancer (IBC), with 4 to 6 weeks of Velbe, Thiotepa, Methotrexate Fluorouracil and Prednisone with Adriblastine added for those patients with IBC or T greater than 7 cm, or N2 N3. Because of tumor regression of more than 50 per cent observed in 80 per cent of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium) and are in a complete remission in all these cases after curietherapy. Maintenance treatment with the same drugs was prescribed for 6 to 18 months depending on the initial staging. Tumor regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest one being 42 months. The overall survival at 2 years for IBC, is 90 per cent with a disease-free survival of 80 per cent. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.
In a retrospective study of 1 094 patients treated for Hodgkin's disease between 1963 and 1976, we have observed 65 malignant complications including 28 granulosis acute leukemias and 37 solid tumors. The actuarial 10 year risk of developing acute leukemia is 4.7 per cent; and 5.4 per cent for solid tumors. These figures vary according to the medications received. They are more important in the case of polychemotherapy, particularly for acute leukemia, thus confirming the specific role of alkyl agents. While the course of solid tumors does not seem to differ from that of identical primitive tumors; on the other hand, induced leukemia seems to have a more perjorative prognosis than spontaneous leukemia and they are often announced by cytopenia. The overall risk of developing secondary cancer is multiplied by 2.4 compared to the normal population; that of developing acute leukemia is multiplied by 9.3. In order to reduce this risk, active non alkyl agents of limited duration must be advocated. Irradiation fields must also be reduced.
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.
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Burkitt's-type leukemias have specific cytologic, immunologic, and cytogenetic characteristics. Initial symptomatology frequently includes abdominal tumors and initial CNS involvement. Despite intensive treatment including high-dose cyclophosphamide, prognosis remains poor in most patients because of failures to achieve complete remission (CR) or because of early relapses, especially CNS relapses. Class III acute lymphoblastic leukemia in children is defined by the presence of two or more unfavorable parameters and recent progress has been achieved by intensive therapy. Cox's multifactorial analysis allows improved discrimination. A phase I protocol for increased-risk leukemias, including testis preventive irradiation and monthly reinductions without continuous maintenance for the first 6 months of CR, seems promising.
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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.
This analysis includes 406 patients who entered a controlled and stratified study of adjuvant chemotherapy after total mastectomy preceded (177 pts) or followed (229 pts) by breast radiotherapy. Negative lymph node (NO) patients (stage I or II) were randomized between no treatment or alkeran (600 mg/m2 x 5 days every 6 weeks). Out of 92 patients 2 relapses in each arm were observed. Relapse free survival at 4 years is 91%. For patients with one to three positive lymph nodes, there is not difference between alkeran and the combination of Vinblastine, Thiotepa, Methotrexate and 5 Fu (VTMF). Relapse free survival at 4 years is 78% for alkeran and 70% for VTMF. For patients with more than 3 positive lymph nodes there is no difference between cyclophosphamide, Methotrexate, 5 Fu (CMF) and CMF VP (Vincristine and Prednisone). We observe no difference between menopausal and other patients. Among the 49 relapses, 5 were local recurrences. The sites of distant metastasis were bone (24 pts), liver (10 pts), lung (9 pts). Advantage of adjuvant chemotherapy is not proved for NO patients. In the other categories, the optimal strategy of chemotherapy with or without hormonotherapy is still to be established.
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.
The cases of one hundred and forty-one patients (85 males, 56 females) treated for hyperleucocytic acute lymphocytic leukemia (H-ALL) were reviewed. In all cases the initial white blood cell count was over 100,000/cu mm. One hundred patients (71%) attained complete remission (CR). The median duration of CR was six months and the median survival was nine months for all patients and 11 months for those who attained CR. Age, initial hemoglobin, and the height of initial white blood cell count over 100,000 had no significant prognostic value. Relapses occurred earlier in patients with a mediastinal mass. The results depended on the treatment used. With modern treatment, including more intensive chemotherapy and central nervous system prophylaxis, CR rate increased from 65% to 81% and median duration of CR improved from four months to ten months. The most important prognostic difference was related to the sex: CR rate was higher (78.5% vs. 66%) and median duration of CR and hematological remission was longer for females (nine months vs. six months and ten months vs. 6.5 months, respectively). This difference only appeared with modern treatments, however: before 1972 the median duration of CR was four months for both sexes, and after 1972, it was eight months for males and 17 months for females. This difference could be explained by the site of the first relapse, which was testicular in only 2% of cases before 1972 and 27% (47% of the males who relapsed) after 1972.
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This report concerns the experimental activity and the preliminary clinical results obtained with detorubicin, an anthracycline. Experimentally, in comparison with doxorubicin, detorubicin is less toxic, less immunodepressive, and less mutagenic, its experimental antitumor activity is equal or superior, and differences are found in pharmacokinetics. Its most interesting activities in clinical cancer therapy are found in non-Hodgkin lymphomas, in carcinomas, and in soft-tissue sarcomas.