Report on the European Workshop on Peripheral Blood Stem Cell Determination and Standardization--Mulhouse, France, February 6-8 and 14-15, 1992.
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Biomedical subjects
Publications and source records attributed to P Henon.
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In this report we review meeting highlights. Clearly there has been substantial progress in the laboratory and clinic with regard to blood stem cells. Having proven that these transplants work, it is now time to investigate biologic features in greater detail. Also needed are randomized trials evaluating several of the issues we raise such as whether the better results of blood cell autotransplants are due to more effective treatment or subject selection and whether in vitro removal of tumor cells is necessary or effective.
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A controlled multicentre trial was conducted in France over a period of five years in 40 patients with thrombotic thrombocytopenic purpura (TTP) to try to determine the best treatment of this disease. Patients presenting eligibility criteria were centrally randomized into two therapeutic groups: Group A) daily plasma exchanges with a solution of fresh frozen plasma (15 ml/kg) in albumin (45 ml/kg) versus Group B) daily transfusions of fresh frozen plasma (15 ml/kg), both systematically associated with intravenous antiplatelet therapy. When the treatment was started early after the first symptoms of TTP, there was no significant difference among plasma exchange and plasma transfusion. But the later the treatment was started, the lesser was the initial therapeutic response and the poorer the prognosis. Furthermore, the excessive use of plasma transfusions in initially unresponsive patients could be dangerous, resulting in some cases in irreversible development of the disease. The overall survival rate in groupe A was 85 percent with 80 percent complete remissions and 15 percent deaths, as opposed to a 57 percent survival rate with 52 percent complete remission and 43 percent deaths in groupe B. Thus plasma exchanges with fresh frozen plasma if started early and performed daily in sufficient amounts, appear to be undoubtedly safer than plasma transfusions.
We report a case of acute non lymphoblastic leukemia in which clinical and cytological patterns corresponded closely to the M3 variant as defined in the FAB classification, although we did not find the characteristic t (15; 17) chromosomal translocation. However, cytochemistry, DNA content studies and immunophenotyping showed unusual patterns suggesting a monocytic differentiation of most of the blast cells, while a smaller population of blasts showed in contrast typical markers of granulocytic lineage.
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The level of circulating myeloid progenitor cells (CFU-G), considered to be a good index of the quantity of circulating hemopoietic stem cells, was measured in the peripheral blood of 5 patients with acute leukemia as they entered first remission. High levels of circulating CFU-G were found in 4 of these 5 patients, depending on the intensity and the number of courses of induction chemotherapy. Repeated cytaphereses were done on 3 of these patients in order to collect and to cryopreserve circulating stem cells, to be used later for autologous transplantation. We propose a model which calculates the number of cytaphereses sufficient to obtain a level of 10(5) CFU-G/kg of weight, considered necessary to achieve a good hemopoietic reconstitution after transplantation.
A comparative study of the heterogeneity of the platelets volumes has been carried out in 9 patients with primary myeloid splenomegaly on their admission to hospital and during the evolution of their disease and in 40 healthy controls. The measurements were performed using a Coulter S-Plus system and different indexes have been calculated to better define the distribution of platelet volume. Platelet size distribution measurements demonstrated a double peculiarity in myeloid splenomegaly: an excessive microcytosis associated with a semi-linear and non log-normal distribution of macrothrombocyte volume. These data may be used as a good marker for the diagnosis of primary myeloid splenomegaly.
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A study of neutrophil functions has been performed in 17 patients with advanced cancer and in 21 controls. Their phagocytic activity, their index of reduction of NBT and their myeloperoxidase activity were examined. The reslts suggest that cancer patients might have a "factor" or "factors" in their plasma which interfereu (s) with phagocytosis and which promote (s) exocytosis of lysosomal enzymes ("reverse endocytosis") from from autologous polymorphonuclear leucocytes as well as from cells obtained from normal healthy donors.
Before starting any therapy, we systematically studied by biopsy the bone marrow of 66 patients suffering from various cancers and suspect of marrow metastasis. Metastatic cells were thus found in 45 patients. Bone marrow composition was examined on histologic sections by granulometric method, while relative proportions and morphology of the various hematopoietic series were examined on cytologic prints. It then appeared that any important metastatic invasion goes together with deep alterations of the surrounding hematopoietic tissue, with frequent peri-metastatic collagenic fibrosis and hypoplasia of the various cell-lines; when metastatic growth is still moderate, hematopoietic tissue is, on the contrary, often hyperplastic, "irritative". These marrow alterations are not to be found far from the metastasis, and thus seem to be directly linked to the actual presence of cancerous cells.
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