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Biomedical subjects

G Flandrin

Publications and source records attributed to G Flandrin.

At least 181 records · Page 10Linked to original sources

Proposals for the classification of the myelodysplastic syndromes.

New diagnostic criteria for the diagnosis of the various myelodysplastic syndromes (MDS) are proposed, and a detailed description is given of the features that may help define MDS. Five MDS are described: (1) refractory anaemia (RA), (2) RA with ring sideroblasts, (3) RA with excess of blasts (RAEB), (4) chronic myelomonocytic leukaemia (CMML), and (5) RAEB 'in transformation'. One of the main distinguishing features of these conditions is the proportion of blast cells in the peripheral blood (PB) and/or bone marrow (BM). The morphological features of the blast cells that are of diagnostic importance have been redefined. In RA, with or without ringed sideroblasts, there are fewer than 1% of blasts in the PB and fewer than 5% in the BM; RAEB is defined as having between 5% and 20% of blasts in the BM and fewer than 5% in the PB; RAEB in transformation (a newly defined category) will be considered when any of the following features is present: (i) more than 5% of blasts in the PB, (ii) 20-30% in the BM, and (iii) the presence of Auer rods in granulocyte precursors in BM or PB. In accordance with these newly defined criteria, it is now proposed that over 30% of bone marrow blasts will suffice for the diagnosis of acute myeloid leukaemia (AML) in any of its forms (M1-M6). The proposed descriptions of the MDS should facilitate the interpretation of data emerging from cytogenetic and bone marrow culture studies and the search for features of possible prognostic significance. Recognition of the new category, RAEB in transformation, may throw light on the pathogenesis of AML.

Anemia, Aplastic↗

[Hairy cell leukaemia with severe bone marrow insufficiency. Complete remission after chemotherapy in two patients (author's transl)].

Comple remission was obtained in two patients with hairy cell leukaemia and severe bone marrow insufficiency, using combined chemotherapy (rubidazone, arabinosyl cytosine, 6-mercaptopurine and cyclophosphamide). The remissions -- as demonstrated by normal blood cell counts and differentials and complete disappearance of hairy cells and fibrosis in bone marrow biopsies -- have now persisted for 6 and 3 months respectively. Intensive chemotherapy should be considered in patients who, after splenectomy, still have severe bone marrow depletion with persistent anaemia, neutropenia and/or life-threatening thrombocytopenia. Protected environment in a haematology intensive care unit is a prerequisite of intensive chemotherapy in such patients.

Antineoplastic Agents↗

Malignant lymphoma supervening in chronic lymphocytic leukemia and related disorders. Richter's syndrome: a study of 25 cases.

Richter's syndrome (RS) has been defined as "histiocytic" lymphoma (HL) or Hodgkin's disease (HD) supervening in the course of chronic lymphocytic leukemia (CLL) and related disorders. The clinical, histologic, and immunologic findings in 25 cases (11 women, 14 men) of RS are presented. The initial diagnosis was CLL in 19 cases, diffuse well-differentiated lymphocytic lymphoma in 2 cases, and Waldenstrom's macroglobulinemia in 4 cases. The interval between the initial diagnosis and that of RS ranged from 0 (two cases) to 120 months (median 49 months). At the time of diagnosis of RS, the initial lymphoproliferative disorder was in apparent complete remission in only two cases. The lymphoma was disseminated in at least 18 cases. The overall median survival was four months, but complete remission was achieved in six cases and has been maintained for 15 to 77 months. In four of these six cases, the RS was localized. The histologic diagnosis of HD was made in only two cases. In the other 23 cases, the diagnosis was HL, but in five of these cases, the proliferation was heterogeneous and was considered as an early aspect of HL. Immunologic studies of lymph node cell suspensions were performed in seven cases. In all cases, the B-lymphocytic origin of the lymphoma cells could be ascertained. Detailed studies in four cases showed that lymphoma cells carried SIg of the same isotype and light chain type as that of SIg detected on CLL cells or of monoclonal serum Ig. In these cases, the lymphoma was actually related to the initial B-cell chronic lymphoid disease.

Adult↗

[Translocation t (8; 21) and acute granulocytic leukemia: interpretation of normal mitoses].

Cytological and cytogenetic studies of nine acute granulocytic leukemia with t (8; 21) translocation were performed from the same bone marrow and blood cell samples. It was shown that the chromosome abnormality was restricted to leukemic cells and that normal metaphases were erythroblast mitoses. Using cell cultures in which only or mainly leukemic cells were able to divide permits easier detection of chromosomal aberrations. These results led us to postulate an inhibitory role of leukemic cells on the division of normal granulocytic cells.

Cell Division↗

The morphological classification of acute lymphoblastic leukaemia: concordance among observers and clinical correlations.

The degree of concordance in the morphological classification of ALL was assessed by the FAB group after two successive reviews of 200 and 100 slides respectively. As a result, a simple scoring system for types L1 and L2 is proposed based on the following four features: (1) nuclear cytoplasmic ratio, (2) presence, prominence and frequency of nucleoli, (3) regularity of nuclear membrane outline, and (4) cell size. By this method, the overall concordance by seven observers (agreement of 7:0 or 6:1 only) increased from 63% to 84%. A significant difference in the incidence of the ALL morphological types in children (less than or equal to 15 years) and adults (greater than 15 years) was found: 74% of L1 cases were children while 66% of L2 cases were adults (P less than 0.001). No significant differences were observed in the incidence of L3 in children and adults or between L1 and L2 according to the membrane phenotype of the blast cells. All L3 cases had B-cell characteristics. A better prognosis for L1 and a higher relapse rate for L2 has been found in several recent reports; The present study may facilitate the morphological analysis of ongoing clinical trials in ALL by improving the reproducibility of the FAB classification.

Acute Disease↗

Chemotherapy-radiotherapy versus chemotherapy in Hodgkin's disease with bone marrow involvement. Retrospective analysis of 32 cases.

A retrospective analysis was performed on 32 patients suffering from Hodgkin's disease with bone marrow involvement treated between 1972 and 1976. After 6 courses of chemotherapy (MOPP for 25 patients), we observed 20 complete remissions (62.5%), 8 lymph node partial remissions (bone marrow sterilization but persistence of pathological lymph nodes) and 4 failures. among the 28 complete or partial responders, 17 received maintenance chemotherapy alone, 9 were submitted to 40 Gy and 2 to 20 Gy irradiations. 15 patients died and 8 relapses occurred - all in previously involved lymph node areas. Survival of complete and partial responders is significantly different (p = 0.01) according to whether they received maintenance chemotherapy alone (34.5%) or irradiation (75.7%). Disease-free duration is also significantly different (p = 0.05) according to whether the patients received maintenance chemotherapy alone (42.1%) or 40 Gy irradiation (100%).

Adolescent↗

Acute lymphoblastic leukemia with Burkitt's lymphoma cells: membrane markers and serum immunoglobulin.

Blast cells from 24 patients with acute lymphoblastic leukemia of Burkitt's cell type were studied for lymphocyte surface markers. The leukemia cells were of B-cell origin in 23 cases and showed a non-B, non-T phenotype in 1 case. Surface immunoglobulins on blast cells were monoclonal, with a striking predominance of cases with light chains of lambda type. They consisted most often of high-density IgM usually without associated IgD. However, 3 patients had cells with surface IgG and 1 had surface IgA. The blast cells lacked detectable IgG Fc receptors in more than half the patients. Serum immunoglobulins were studied in 15 cases: A monoclonal IgM was found in 5 patients (whose blast cells had surface IgM) and a Bence Jones protein was found in 2 others, both of whom had blasts with surface IgG lambda.

Adolescent↗

Cell surface characterization of malignant T cells from lymphoblastic lymphoma using monoclonal antibodies: evidence for phenotypic differences between malignant T cells from patients with acute lymphoblastic leukemia and lymphoblastic lymphoma.

A series of monoclonal antibodies was used for the characterization of malignant T cells from 21 patients with lymphoblastic lymphoma (LL). The tumor population from these patients showed a marked degree of phenotypic heterogeneity and a proportion (one-third) of patients had tumor cells that did not conform exactly with the cells normally detected in the thymus. However, these cell populations could be related to the early or common or late thymocyte population (about one-third of the patients in each category). This contrast, with the characterization of malignant T cells from 43 patients with acute lymphoblastic leukemia (ALL) that could be related to either early or common thymocytes, with an exception of two patients categorized as having a tumor population related to late thymocytes. Further phenotypic differences between cells from ALL and LL could be demonstrated by investigation with two additional monoclonal antibodies, A50 and U4. Among patients with malignant T cells related to common thymocyte, 0/12 patients with ALL had cells recognized by A50, where 5/8 patients with LL had A50+ cells. Among patients with early thymocytes, only patients with ALL had cells recognized by U4. In addition, 5 LL patients had cells reactive with J5, a monoclonal antibody recognizing the common ALL antigen (CALLA). Since CALLA was found on cells related to common and late thymocytes, CALLA is neither lineage specific, nor can it be viewed as being peculiar to malignant lymphoid cells arrested at very immature stages of differentiation.

Adolescent↗

Karyotypes and cell phenotypes in acute leukemia following other diseases.

Acute nonlymphoblastic leukemias following other blood disorders or exposure to possible oncogenic agents were analyzed for cytological and cytogenetical characteristics. "Secondary' acute leukemias (AL) were often found to be unclassifiable in the FAB system. Monosomy 7 was associated with megakaryocytic cell line abnormalities. Variation of cytological and cytogenetical patterns was correlated in the whole sample and in a sample of 10 postpolycythemia vera blood disorders.

Chromosome Aberrations↗

Surface antigens on malignant Sézary and T-CLL cells correspond to those of mature T cells.

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T-cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sézary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T-chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.

Antibody Specificity↗

[Congenital deficiency of platelet alpha-granules and medullary reticulinic fibrosis. Physiopathogenic hypothesis (author's transl)].

Hematological investigations of two propositus from a family with congenital thrombopathia characterised by a moderate thrombopenia and a specific platelet alpha granule deficiency revealed that the thrombopathia was associated with a constitutive reticulinic myelofibrosis, without any sign of evolutivity. This association led us to present an hypothesis to explain the genesis of this myelofibrosis. This hypothesis is based on the potential role of a mitogenic factor(s) synthetized in megakaryocytes and transported normally by platelets in alpha granules, to induce fibroblastic proliferation and increased synthesis of collagen type III by bone marrow. This myelofibrosis is similar to that found in most of myeloproliferative disorders at some step of evolutivity. In these diseases myelofibrosis is associated with qualitative and quantitative abnormalities of platelets and megakaryocytes. These abnormalities give elements to sustain our hypothesis.

Blood Platelet Disorders↗

[Automatization of differential leukocyte counts with image analyzer. Comparison between three apparatus (author's transl)].

The choice of an automated differential leukocytes counting system depends on a number of criteria including reliability, speed an cost/effectiveness ratio. We have compared the performance of three commercially available instruments, the Hematrak 360 (Geometric data), the ADC 500 (Abbott) and the DIFF 3 (Coultronics). We have voluntarily confined this study to pattern recognition systems and have not investigated other systems based on cell volume determination and cytochemical reactions (Hemalog D, Technicon). Comparison of a new system with an established automated system simplifies the task considerably, provided that the quality and performance of the reference system have been previously well-established, as has been done in our laboratory with the LARC which has been evaluated comparatively to the traditional method (5). A final difficulty is that the conclusions drawn from this type of study cannot be considered as definitive insofar as changes and improvements are continually being proposed for all systems which are still going through a mutation stage as we noticed in the course of this evaluation.

Blood Cell Count↗

Karyotype and cell phenotypes in primary acute leukemias.

This paper reviews the chromosomal and cytological patterns in acute leukemias (AL) and attempts to establish a correlation with the FAB classification. In fact, these studies are useful in distinguishing different forms of AL and in understanding the nature of the cell from which the malignant clone originated. As shown by the results obtained from the study of acute promyelocytic leukemia, for instance, these studies also provide a likely explanation for the lack of chromosome abnormalities in certain cases of AL.

Acute Disease↗

[Induced leukemias. Cytogenetical and cytological aspects. Comparison with primitive leukemias (author's transl)].

25 presumably induced leukemias, either following treatment (lymphoma, polycythemia vera, essential thrombocythemia, cancers) or after exposure to oncogenic agents have been studied cytogenetically and cytologically. Complex chromosomal abnormalities were associated with a difficult cytological classification. Complete monosomy 7 with presence of micromegacaryocytes and macroplatelets was observed in 7 cases. The findings observed in induced leukemias were compared with those found in "primitive" leukemias showing the same chromosomal patterns. The same relationships between cytology and cytogenetics have been observed.

Adult↗