Repeated high-dose-melphalan with autologous bone marrow transplantation in acute non lymphocytic leukemia.
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Biomedical subjects
Publications and source records attributed to G Sebahoun.
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Peripheral T-lymphocyte reconstitution after bone-marrow transplantation, 12 allogeneic and 13 autologous, was studied by indirect immunofluorescence assay using mouse monoclonal antibodies. Abnormal counts were detected in the two major sub-populations of T-cells i.e. helper and T cytotoxic-suppressor lymphocytes, defined by monoclonal antibodies (alpha Leu 3a and B 9.2), and in DR antigen-positive T-cells. The pattern of T-lymphocytes replenishment was identical for both types of transplant, and was not affected by Graft Versus Host disease (GVHD).
Large series of patients with hairy cell leukaemia have only recently been published. The 211 cases reported here provide useful information on the clinical presentation, prognostic factors, evolution and management of this uncommon disease. At presentation, 28% of the patients had no spleen enlargement, and only 20% had severe pancytopenia. However, severe neutropenia (less than 0.5 X 10(9)/l) was present in 32% of the cases. Prognosis was primarily related to the degree of peripheral cytopenia, usually corrected by splenectomy, but it was poor in both non-splenomegalic and splenectomized patients with persistent anaemia and neutropenia, and it is in these patients that other treatments should be tested.
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High-dose melphalan followed by "rescue" with autologous marrow stored for 12-24 hours at room temperature was used in the treatment of 14 patients with advanced tumors refractory to conventional treatment. Twelve patients were evaluable, with three complete responses (25%), five partial responses (42%), and two minimal responses (16%). Response durations ranged from 4 to 38 weeks (median, 7). There were two treatment-related deaths and one patient developed acute nonlymphocytic leukemia 3 months after a second course of high-dose melphalan.
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Seven patients with relapsed acute leukaemia were treated with high-dose melphalan (HDM) followed by the infusion of autologous cryopreserved remission marrow. Toxicity was minimal and all seven patients had a complete response. Four patients are still in unmaintained remission at 14, 13, 10, and 3 months, the first two having received a second course of HDM to consolidate the result. The role of HDM as a form of intensification therapy for patients with acute myeloid leukaemia in first remission should be investigated.
Granulocytic progenitor cells (CFC) are a better reflection of stem cell pools than precursors. Their total number can be estimated during hematologic steady-state (N = 70 +/- 29 x 10(5) CFC/kg); the amount of marrow necessary to perform a bone marrow transplantation is only 1% of the total pool. CFC are useful but have a mainly qualitative value in evaluating the viability of marrow stored for 24 h at room temperature (92%) or marrow thawed after DMSO cryopreservation (62%). Sequential study of CFC in patients receiving autologous marrow transplantation enables differentiation of engraftment from autologous recovery. In 11 recipients of autologous marrow transplantation, no statistical relation was observed between number of infused CFC and severity of granulocytopenia. Further studies will be necessary to evaluate a better marker of real hematopoietic stem cells.
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Septicaemias are frequent and severe in patients with acute leukaemia under aplastic treatment. The present study concerns 69 such patients: 29 with acute lymphoblastic leukaemia (ALL), and 40 with acute non-lymphoblastic leukaemia (ANLL). All were treated in single rooms in the same hospital and in similar conditions. The overall incidence of septicaemia was 62%; it was 60% in patients with recently diagnosed ALL and 68% during relapses. More than 34% of ALL patients and 82.5% of ANLL patients had one or several episodes of septicaemia. Among the 74 pathogens isolated 50% were Gram-positive organisms, 45% Gram-negative organisms and 5% Candida spp.. The first episodes of septicaemias were predominantly caused by Gram-positive spp. (61%) and the subsequent ones by Gram-negative spp. (60%). The primary infection could only be diagnosed in 19% of the cases and was most frequently located in the digestive tract or perineal region. The most common focal complications were lung infections (18 cases), skin infections (12 cases) and septic shock (15 cases). Seventy-four p. cent of the patients survived with prompt and potent antibiotic therapy. Death occurred in 26% and was clearly related to the following factors: chemotherapy of relapsed leukaemia and/or blastic aplasia and/or successive episodes of septicaemia. The incidence and severity of septicaemias in leukaemic patients will only be reduced by improved prophylactic measures against infection and by less pronounced and shorter chemotherapy-induced granulocytopenia.
A trial of maintenance chemotherapy of nonlymphoblastic acute leukemia led to a comparison of two groups of patients in complete remission. Group 1 (14 patients) received only monthly reinduction chemotherapy. Group 2 (17 patients) received identical chemotherapy together with weekly immunotherapy combining BCG and irradiated leukemic cells. While the duration of the first complete remission was unmodified, the overall survival time and, above all, survival after the first relapse were prolonged in group 2 chemoimmunotherapy. These results were all the more marked when a homogeneous group of patients having received the same induction chemotherapy were considered.
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A case of acquired dyserythropoiesis with inter-erythroblastic connections is reported in a patient with chronic myeloid leukaemia, developing a terminal acute hepatic failure related to hepatocarcinoma. The erythroblastic series was abundant but only made of clusters grouping 10 to 20 closely adherent cells. The cellular membranes showed linear junctions or were interdigitated and the intercellular space was occupied with electron dense ferritin granules. This non specific aspect of dyserythropoiesis may be related to the hepatic carcinoma, which was probably induced by busulfan therapy.
Mediterranean visceral leishmaniasis is not only a children disease. We observed 12 adult cases since 1971. Clinical presentation usually associates anarchic fever and splenomegaly, with anaemia, leucopenia, increased sedimentation rate and hypergammaglobulinemia. We must think to kala-azar, specially after a stay in an endemic country (mediterranean area), ask for parasites on bone-marrow smears and more often immunological diagnosis. Spontaneously fatal, the disease is easily cured by antimony derivatives.