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Biomedical subjects

M Bizet

Publications and source records attributed to M Bizet.

At least 19 recordsLinked to original sources

Mature plasma cells as indicator of better prognosis in multiple myeloma. New methodology for the assessment of plasma cell morphology.

The relationship between plasmablastic cells and outcome in multiple myeloma (MM) has been established for nearly 15 years. But the assessment of these cells is not easy to perform and it allows the identification of only a small proportion of patients. We investigated the plasma cell morphology using a progressive evaluation of consecutive criteria: nucleolus, chromatin and nuclear-cellular ratio (N/C). The combination of these three items produces a subclassification where four cellular subtypes identify 93% of the plasma cells, and these subtypes are related to the outcome. The interest of this methodology is to be based on the mature plasma cells that are easier to identify than the plasmablastic cells. These new cell subtypes introduce a new classification for patients: Group 1 includes patients with at least 66% mature plasma cells (P000). Both Group 2 and 3 have less than 66% P000 and are separated by their degree of maturation (Proplasma I > or = Proplasma II + plasmablastic). The distinction of these three groups of patients is highly related to the prognosis (P < 10(-4)). These results have been confirmed on a second group of patients coming from a different institution. In conclusion, we propose a new methodology for the plasma cell evaluation in MM, that is based on the morphological criteria and that has the advantage of identifying an intermediate (30%) subgroup of patients with a prognostic significance.

Algorithms↗

Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value.

Twenty-two B-cell chronic lymphocytic leukemia (CLL) patients were investigated to evaluate residual disease in clinico-hematological remission. Residual disease was determined by monotypy of surface light-chain expression and by dual-color staining with CD5 and CD19 markers. Samples were analyzed on flow cytometer. Total CD19+ cells above 25%, the CD5+CD19+/total CD19+ cells ratio above 0.25, clonal excess above 0.4 were considered positive for residual disease. According to these immunological criteria, only four cases achieved phenotypic remission. Our data confirm that dual marker analysis is more sensitive than clonal excess and may predict an early relapse. Ig gene rearrangements were studied by Southern blot analysis using IGHJ and IGKC probes in fifteen cases. All 12 cases that retained a detectable rearrangement displayed a phenotypic residual disease. Conversely, in two cases, DNA analysis failed to detect the residual disease characterized by flow cytometry. In conclusion, this study suggests that in B-CLL, dual marker analysis is sensitive in predicting an early relapse in sequential evaluations of residual disease, whereas rearranged bands are undetectable when the proportion of malignant cells is low.

Adult↗

Expression of the hyaluronan-binding glycoprotein hyaluronectin in leukemias.

Hyaluronectin (HN), a hyaluronan (hyaluronic acid, HA)-binding glycoprotein is normally expressed in the nervous system, found in the desmoplasia of tumours, and is also produced in vitro by peripheral blood mononuclear cells. We have therefore investigated the expression and the production of HN by leukemic cells, with the hypothesis that HN would be expressed in leukemias of the myeloid lineage. Fresh and frozen leukemic cells were studied from 70 patients of whom 53 had acute myeloblastic leukemia (AML). HN was strongly expressed (> 80% blood cells) in two out of 13 M4 AMLs and four out of four M5B AMLs. One further M4 AML displayed 25% positive cells and two 20% cell positivity cases were seen, in one case of M4 AML and in one case of chronic myelomonocytic leukemia (CMML). The rest of the cases of AML as well as all cases of acute lymphoblastic leukemia (ALL) showed almost no positivity (< 1%). The residual positive cells appeared to be normal blood promonocytes. Taken together > or = 20% positive cells was seen in eight out of 56 (14%) examined myeloid leukemias. The HN production was significantly higher (p < 0.0001) in cell culture media of M4 and M5 AML cells than in other AML or ALL cell culture media. A significant correlation was found (p < 0.0001) between the number of HN-positive leukemic cells and the number of cells with a monocytic morphology, suggesting that HN is a marker for the promonocyte.

Acute Disease↗

Heterogeneity of acquired idiopathic sideroblastic anaemia (AISA).

Clinical, haematological and outcome data were studied in 84 patients with acquired idiopathic sideroblastic anaemia (AISA) from a registry of 613 consecutive myelodysplastic syndromes (MDS) recorded by five institutions in western France. Two groups could be identified and compared: 'pure' erythroblastic AISA (AISA-E: 59 pts), and AISA with myelodysplastic features, i.e. dysgranulo and/or dysmegakaryopoiesis (AISA-M: 25 pts). Results were also compared to those of a series of 71 cases of refractory anaemia without sideroblastosis (RA) carried out from the same registry. Dyserythropoiesis was present in 90% of all AISA subtypes, dysgranulopoiesis in 88% of the AISA-M cases; dysmegakaryopoiesis was observed in 44% of AISA-M. Ten patients with both forms of AISA showed high platelet counts. These cases appeared particular in that four of them were associated with a splenomegaly and/or a hyperleucocytosis. They had to be distinguished from myeloproliferative syndromes. Outcome comparison of AISA-E with AISA-M showed a significant discrepancy of survival duration (60 vs 38 months respectively). Progression towards refractory anaemia with excess of blasts or acute leukaemia, was significantly higher for AISA-M than for AISA-E. The risk of transformation increased to 24% for the AISA-M group similarly to those of RA patients (17%). We conclude that AISA must be divided into two categories, 'pure' AISA and AISA-M, because survival duration and risk of transformation are different.

Aged↗

[Recurrent syncope during deglutition. An uncommon form of sinusal dysfunction].

The authors report the case of a 69 year old man with a 16 year history of syncope occurring only while swallowing liquids. Two episodes were observed during a hospital admission to the intensive care unit for unstable angina and allowed documentation of prolonged sinus arrest (7 sec) causing syncope. In the light of this case and a review of the literature, the physiopathological role of deglutition in the genesis of cardiac conduction defects and arrhythmias is discussed and the new classification of sinus node dysfunction proposed by Bashour in 1985 is recalled.

Aged↗

Cytogenetic studies in untreated Hodgkin's disease.

Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11-13, 13p11-13, 3q26-28, 6q15-16, and 7q31-35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11-13 (P less than .01), 13p11-13 (P less than .01), 14p11 (P less than .01), 15p11-13 (P less than .02), and 20q12-13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12-13 (P less than .01) and 13p11-13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.

Adolescent↗

Prognostic factors of myelodysplastic syndromes--a simplified 3-D scoring system.

From 1 January 1982 to 31 December 1986 in five haematological centers of the west of France (Rennes, Rouen, Nantes, Tours and Angers), we have collected 503 cases of myelodysplastic syndrome (MDS). These cases were classified by FAB recommendation as followed: 85 refractory anemia with ring sideroblasts (RARS); 273 refractory anemia in which 86 were without blasts (RA), 153 were with excess of blasts (RAEB) and 34 were with excess of blasts and in transformation (RAEB-t); 111 chronic myelomonocytic leukaemia (CMML); and 34 cases with borderline features. The point date for statistical study was 31 December 1988, and the scoring method of Bournemouth was applied to compare with our findings (62% resulted in death, 18% in leukemic transformation). It was demonstrated that haemoglobin, platelets, and bone marrow-blasts are the best factors to predict survival or leukaemic transformation (LT). But peripheral neutrophils don't affect the survival time excepted when lower than 500 microliters (13 months vs 19.6 months). A scoring system based on haemoglobin (Hb), platelets (Pl), and bone marrow blasts (BMB) may be represented in a three-dimensional space and is a good tool to know the own value of each parameter. This 3-D system shows that BMB and Pl are the most important factors and are correlated with survival, per cent of death, and LT (p less than 0.0001). The LT is observed in 18% of the whole population. RAEB and RAEB-t progress in AML2 (14.6%) or AML4 (1.4%), and CMML progress in AML2 (8.1%) or AML4 (11.7%). We observed that monocytes are not good parameters to predict the type of leukemic transformation. Furthermore, survival of RA treated with Ara-C(ld) or not treated was similar.

Aged↗

Del(14)(q22) in diffuse B-cell lymphocytic lymphoma.

Some recurrent chromosomal abnormalities have recently been found to be associated with distinctive histologic subtypes of non-Hodgkin's lymphoma (NHL). In a study of 62 patients with NHL whose karyotypes was determined at diagnosis, 3 patients were found to have a deletion of the long arm of chromosomes 14 at band 22 (del[14][q22]). All had a diffuse lymphoma with generalized lymphadenopathy and bone marrow involvement. All three lymphomas were of B-cell origin, as shown by the presence of surface immunoglobulin and monoclonal antibody phenotyping. For each patient, a trisomy 12 was associated with del(14)(q22) in a clone. These data suggest that del(14)(q22), perhaps in association with trisomy 12, could identify a subtype of NHL and that band 22 of chromosome 14 may be implicated in the B-cell ontogeny.

Antigens, Differentiation↗

Simultaneous occurrence of a T-cell lymphoma and a chronic myelogenous leukemia with an unusual karyotype.

The simultaneous occurrence of malignant T-cell lymphoma and chronic myelogenous leukemia is reported. The lymph nodes contained E rosette forming cells. Blood and bone marrow cell morphology were consistent with the diagnosis of chronic myelogenous leukemia. Lymph nodes, bone marrow and blood mitosis showed a t(6;8) (6pter----6q27 ::8p12----8pter;6qter----6q27 ::8p12----8qter) translocation. So far a number of recent reports have shown simultaneous B lymphoid and myeloid proliferations in some malignancies, this is apparently the first reported case of simultaneous T lymphoid and myeloid proliferations.

Adolescent↗

Myelofibrosis and acute megakaryoblastic leukemia in a child: topographic relationship between fibroblasts and megakaryocytes with an alpha-granule defect.

In a child with acute megakaryoblastic leukemia--severe thrombocytopenia and myelofibrosis, EM studies on bone marrow showed a strict topographic relationship between the presence of clusters of abnormal megakaryocytes and the increased number of fibroblasts and extracellular fibers. Megakaryocytes and platelets lacked alpha-granules while the plasma thromboglobulin level was three times the normal level. This suggested that the alpha-granular proteins were synthesized but not retained in alpha-granules. If this occurs, the increased marrow levels of platelet-derived growth factor and factor 4 would favor the proliferation of fibroblasts and the synthesis of collagen, and thereby promote myelofibrosis. After therapy-induced remission, the number of marrow megakaryocytes decreased, the alpha-granules were normally produced, the plasma beta-thromboglobulin level was normal and the myelofibrosis disappeared. These observations suggest that during acute megakaryoblastic leukemia, an acquired gray-platelet syndrome occurs and that the local excretion of alpha-granule proteins triggers the myelofibrosis.

Blood Platelets↗