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Biomedical subjects

G Flandrin

Publications and source records attributed to G Flandrin.

At least 91 records · Page 5Linked to original sources
PubMed1991

Prognostic implication and characterization of the blast cell population in the myelodysplastic syndrome.

The bone marrow smears of 18 confirmed cases of MDS were analyzed carefully for the presence of "hypergranular type III blasts", defined as more than 20 fine azurophil primary granules per cells. The concordance was close to 80% among 5 observers. Thirty-nine percent (7 cases) were reclassified as RAEB-t rather than RAEB. The presence of these hypergranular blasts was not suggestive of increased differentiation but rather leukemic cells. The reassignment of cases altered the median survival for the various subcategories, providing a clearer separation with the introduction of type III blasts than without utilizing these cells which were separated from the promyelocyte family. The introduction of this new blast cell definition in a larger series of patients is recommended to confirm these preliminary observations.

Aged↗
PubMed1991

Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO)

We describe a form of acute myeloid leukaemia (AML), designated AML-MO, with minimal myeloid differentiation, not included previously in the FAB classification. AML-MO cannot be diagnosed on morphological grounds alone as the blast cells are large and agranular, sometimes resembling L2 or, rarely, L1 lymphoblasts, and should be identified by the following features: negative myeloperoxidase (MPO) and Sudan Black B reaction (or positive in less than 3% of blasts), negative B and T lineage markers and expression of myeloid antigens recognized by at least one monoclonal antibody, CD13 or CD33. Other myeloid markers are also often positive and these include CD11b and the enzyme MPO demonstrated by immunocytochemistry and/or electron microscopy analysis. The findings in a group of 10 cases satisfying the criteria for AML-MO are described. AML-MO represents 2-3% of all cases of AML and 1-1.5% of all acute leukaemias. Its clinical and biological significance is not yet apparent but its identification in a larger number of cases may achieve this aim.

Acute Disease↗
PubMed1990

Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I-associated adult T-cell leukemia and chronic myelopathies as seen in France.

Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I-endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2-dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells.

Antigens, CD↗
PubMed1990

B8.7 antigen is present on B-cell precursor acute lymphocytic leukemia. Correlation with the low molecular weight B-cell growth factor responsiveness of these cells.

The purpose of this study was to analyze the expression of B8.7 antigen and its implication in the low molecular weight B-Cell growth factor (LMW BCGF) proliferative pathway at the early stages of the human B-cell differentiation. After an overnight incubation in culture medium of B-cell precursor acute lymphoblastic leukemias (ALL), we demonstrated the presence of B8.7 antigen in 18 of 25 cases (72%). Such an incubation also induced a significant increase in the LMW BCGF responsiveness of ALL cells (P less than 0.03). In addition, we showed a significant correlation between B8.7 expression and the ability of pre-B ALL cells to respond to LMW BCGF. As previously described for normal B cells, the anti-B8.7 monoclonal antibody inhibited the LMW BCGF-dependent proliferation of pre-B ALL cells in a dose-dependent manner. These data indicate that B8.7 antigen is expressed and may be functionally related to the LMW BCGF pathway at the pre-B cell stages of differentiation. These results also suggest that human B-cell precursor ALL are not only phenotypically similar to their normal B lymphocyte counterparts, but are also sensitive to the same immunoregulatory cytokines that control normal cell growth.

Adolescent↗
PubMed1990

High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis.

Human T-cell lymphotropic virus type I (HTLV-I) proviral integration status was examined by Southern blot analysis in peripheral blood mononuclear cell (PBMC) DNA from patients presenting a tropical spastic paraparesis (TSP) and serological evidence of HTLV-I infection. Surface phenotype and morphological aspects of PBMC were also studied. A polyclonal HTLV-I proviral integration was found in the PBMC of the 10 patients studied irrespective of their geographical origin (French West Indies, French Guiana, and Africa), the duration of their clinical illness, or the HTLV-I antibody titer. Furthermore, by dilution experiments and hypothesizing that only one copy of HTLV-I proviral DNA is present in one cell, we estimated that this HTLV-I integration is present in 3% to 15% of their PBMC. All 10 TSP/HTLV-I patients studied had an average of 10% of their lymphocytes abnormal, presenting either a misshapen nucleus or an adult T-cell leukemia/lymphoma (ATL)-like feature. Moreover, an elevated CD4/CD8 ratio associated with the presence of activated T cells with a high level of DR expression was observed in most patients. The significant frequency of viral-positive PBMC and the important load of HTLV-I proviral DNA that we observed in TSP/HTLV-I patients might play an important role in the pathogenesis of this recently identified clinico-virological entity.

Antibodies, Monoclonal↗
PubMed1990

Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease.

The purpose of this study was to evaluate the influence of the number of mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) cycles and the extent of irradiation on the risk of secondary acute nonlymphocytic leukemia (SANLL) after a single combined treatment for Hodgkin's disease (HD). Between April 1972 and May 1980, 462 patients with HD clinical stage (CS) I, II, and III were prospectively treated with three or six cycles of MOPP and supra- and/or infradiaphragmatic irradiation (40 Gy). Four hundred forty-one patients achieved complete remission (CR). By January 1988, 237 patients had been followed-up in first CR for at least 10 years. Ten patients developed SANLL between the 34th and 123rd month of CR. The 15-year SANLL risk is 3.5% +/- 2.7%. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, histology, splenectomy, MOPP chemotherapy, and irradiation extent) showed that the only significant explanatory variable of SANLL risk was the irradiation extent (P less than .002). Using the log-rank test, SANLL risk ranged from 2.2% for supradiaphragmatic irradiation alone to 9.1% for subtotal (STNI) or total nodal irradiation (TNI) (P less than .001). These results strongly suggest that extended high-dose irradiation and MOPP chemotherapy should not be combined for the treatment of HD.

Adolescent↗
PubMed1990

Splenic B-cell lymphoma with villous lymphocytes (SLVL). A lymphocytic lymphoma simulating hairy cell leukemia. A study of 8 cases.

Splenic B cell lymphoma with circulating villous lymphocytes (SLVL) is a lymphoproliferative disorder characterized by the presence in the peripheral blood of atypical B-lymphocytes with hairy appearance. Although the clinical features with massive splenomegaly, absence of peripheral lymphadenopathy and blood cytopenia may mimic hairy cell leukemia (HCL), precise analysis of the morphologic and immunologic features allow differential diagnosis between these two entities. Bone marrow and spleen histology resemble the pattern in chronic lymphocytic leukemia (CLL). We studied 8 patients with this entity illustrating the difficulty of diagnosis between SLVL and HCL.

Aged↗
PubMed1990

T cell receptor delta gene rearrangements occur predominantly in immature myeloid leukemias exhibiting lineage promiscuity.

T cell receptor delta (TCR) genes have been recently identified as rearranging during the early stages of T cell differentiation. We have analyzed the configuration of these genes in 47 unselected acute nonlymphoid leukemias. Morphology, phenotype, immunoglobulin heavy chain, and T cell receptor beta and gamma chain gene configuration were also studied. We have documented TCR delta gene rearrangements or deletions in eight cases using a genomic J delta 1 probe. The comparison of morphological, phenotypical, and molecular findings from these cases with those from control acute myeloid leukemias whose TCR delta genes were in germline configuration show that TCR delta rearrangements occur predominantly in immature leukemia exhibiting extensive lineage infidelity. The most striking feature was the frequent expression of the CD10 antigen. These data show that inappropriate gene rearrangements occur nonrandomly in myeloid leukemias and suggest that common mechanisms may be involved in the regulation of gene rearrangements and in the expression of some differentiation antigens.

Adolescent↗
PubMed1989

Rearrangements of the T cell receptor delta gene in T acute lymphoblastic leukemia cells are distinct from those occurring in B lineage acute lymphoblastic leukemia and preferentially involve one V delta gene segment.

Rearrangement of the TCR-delta gene was studied using J delta, C delta, and V delta probes in 61 cases of acute lymphoblastic leukemia (ALL) and several cases of chronic lymphoid neoplasms to define the specificity and the diversity of rearrangements occurring at the delta locus. TCR-delta rearrangements or deletions were found in all T (33 cases) and B lineage (28 cases) ALL but not in any case of B cell chronic proliferations (13 cases). The restriction patterns of rearrangement were clearly distinct between T and B ALL and use of one V delta probe showed that rearrangement of the V delta IDP2 gene segment which is also productively rearranged in the Peer cell line, occurred frequently in T-ALL but never in B lineage ALL. Studies of WT31 and delta TCS1 antibody reactivity showed that at least 4 of 13 CD3+ T-ALL cases expressed the delta protein. CD4 and/or CD8 Ag expression were observed in some of the gamma delta expressing T-ALL. These data show that particular TCR-delta gene rearrangements occur in neoplastic early B cells and that the combinatorial diversity of TCR-delta rearrangements in T cells is higher than initially expected. In addition this study shows that an important proportion of CD3 positive T-ALL cases express the gamma delta heterodimer.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

alpha-IFN treatment does not induce Ki-ras expression in hairy-cell leukemia patients.

alpha-Interferon (IFN) is effective in the treatment of hairy-cell leukemia (HCL), but the treatment is sometimes over a long period. Biological changes such as the increase of tumorigenicity can occur rapidly in vivo as a result of beginning this treatment; an increase in c-Ki-ras oncogene expression has also been observed. In order to determine whether the findings observed in vitro would be duplicated in an in vivo system, we decided to analyze the Ki-ras RNA and protein levels in the lymphocytes of three HCL patients, compared with these levels in seven normal donors and one non-treated HCL patients. Ki-ras was not activated by IFN, at least not in lymphocytes. Therefore, the data suggest that the drug could be used for long-term therapy with relatively low risk to the patients.

Gene Expression Regulation↗
PubMed1989

The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias.

We measured the human pim-1 protooncogene (PIM) expression during fetal development and in hematopoietic malignancies. Our data indicate that during human fetal hematopoiesis the 33-kDa pim product, p33pim, is highly expressed in the liver and spleen. In contrast, at the adult stage it is only slightly expressed in circulating granulocytes. Out of 70 hematopoietic malignancies analyzed, 51 patients and 19 cell lines, p33pim was overexpressed in approximately 30% of the samples, particularly in myeloid and lymphoid acute leukemias. This overexpression was unrelated to any stage of cellular differentiation and was not due to gene rearrangement or amplification. These results imply a physiological role of the pim-1 protooncogene during hematopoietic development and a deregulation in various leukemias.

Adult↗
PubMed1989

Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group.

Peripheral blood, bone marrow films, and bone marrow biopsy specimens from 110 patients, well characterised by clinical and laboratory studies, including electron microscopy, were reviewed, to determine proposals for the classification of chronic (mature) B and T cell leukaemias. On the basis of cytology and membrane phenotype the following disorders were defined: (i) B cell type: chronic lymphocytic leukaemia (CLL); CLL of mixed cell type, which includes cases with more than 10% and less than 55% prolymphocytes (CLL/PL), and a less well defined form with pleomorphic lymphocytes but less than 10% prolymphocytes; prolymphocytic leukaemia (PLL); hairy cell leukaemia (HCL); HCL variant; splenic lymphoma with circulating villous lymphocytes; leukaemic phase of non-Hodgkin's lymphoma (follicular lymphoma, intermediate, or mantle zone lymphoma and others); lymphoplasmacytic lymphoma with peripheral blood disease (mostly Waldenström's macroglobulinaemia); and plasma cell leukaemia. (ii) T cell type: T/CLL, which was differentiated from reactive T/lymphocytosis; T/PLL; adult T cell leukaemia/lymphoma; and Sézary's syndrome. The recognition of distinct entities within the B and T cell leukaemias seems to have clinical and epidemiological connotations. It is hoped that these proposals may serve as the basis for further work, discussion, and improved management of patients.

Adult↗
PubMed1989

Gelatinous transformation of the bone marrow: manifestation of an acute leukemia?

Gelatinous transformation of the bone marrow in a 79-year-old patient was observed. It was associated with acute leukemia diagnosed on the biopsy of a vertebral body, indicated by previous Indium-transferrin scintigraphy. Though the lesion is usually associated with severe weight loss and cachexia, the rare cases of gelatinous transformation reported among patients with malignant disease are summarized. It is suggested that metastatic changes by blast cells in acute leukemia may lead to gelatinous transformation of bone marrow but this remains to be investigated.

Acute Disease↗
PubMed1989

Detection of retrovirus particles and reverse transcriptase activity in mid-term cultured peripheral blood and lymph node cells from a French woman with Sezary syndrome.

Retrovirus particles, with an ultrastructure of type C-virus similar to HTLV-I were observed in several mid-term cultures of leukemic cells derived from a woman with a well characterised Sezary syndrome who had always resided in France. Reverse transcriptase activity was detected in supernatant fluids from day 6 to day 40 of culture. However, negative anti HTLV-I serology and the absence of specific molecular hybridization between leukemic cell DNA and two HTLV-I derived probes, argue against a HTLV-I virus.

Aged↗
PubMed1989

Hairy cell leukemia: follow-up after completion of alpha interferon treatment.

Between May 84 and December 85, 61 patients were treated for hairy cell leukemia by (recombinant or natural) alpha-IFN in a single institution. The responses obtained after 7 or 12 months of treatment are presented and the follow-up of the 39 patients for whom the treatment had been stopped for more than 12 months is evaluated. Neither clinical or histological parameters at presentation nor the type of timing of the interferon used allowed to predict the quality of response. The median time-lapse before the occurrence of neutropenia below 1.10(9)/l in patients with normal blood counts at the end of treatment was 12 months. However early relapses after the treatment stop were observed more frequently in patients with initially severe neutropenia or hyperleucocytosis. The therapeutic strategy in hairy cell leukemia is discussed.

Female↗