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Biomedical subjects

M Ffrench

Publications and source records attributed to M Ffrench.

At least 55 records · Page 3Linked to original sources
PubMed1992

Long-term outcome and sequelae in aggressive lymphoma patients treated with the LNH-80 regimen.

One hundred patients with aggressive malignant lymphoma treated with the LNH-80 regimen were evaluated for long-term survival, late relapse and long-term sequelae. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. The fifty-two long-term responders were evaluated for their ability to resume work, sexual function, fertility and presence of long-term sequelae. Of the 41 patients who worked before diagnosis of their disease, 66% had resumed their normal jobs and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) were considered to have mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had second neoplasias. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity.

Adolescent↗
PubMed1992

[Prognostic factors, late relapse and outcome of patients with aggressive malignant lymphoma: long term results of LNH-80 protocol].

The 100 patients with aggressive malignant non Hodgkin lymphoma treated with the LNH-80 regimen were evaluated for long-term survival and quality of life. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two patients are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. Factors adversely correlated with response in multivariate analysis were poor performance status, bone marrow involvement and the presence of more than one extranodal site. Factors adversely correlated with survival were age, high grade subtypes, and bone marrow involvement. The fifty-two long-term responders were evaluated for quality of life parameters such as working ability, sexual function, fertility and absence of long-term sequelae. Of the 41 patients who worked before disease, 66% had resumed their normal job and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) considered having mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had a second neoplasia. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity.

Adolescent↗
PubMed1992

Continuous-infusion daunorubicin and carboplatin for high-risk acute myeloid leukemia in the elderly.

Since continuous infusion of daunorubicin and of carboplatin have shown efficacy and reduced toxicity in early phase studies in acute myeloid leukemia (AML), 34 elderly patients with high-risk AML were treated with continuous infusion daunorubicin, 30 mg/m2 per day, from day 1 to day 4, and carboplatin, 200 mg/m2 per day from day 3 to day 7. Seven patients had therapy-related AML and/or AML following a myelodysplastic syndrome at diagnosis, 15 were in first and two in second relapse, and 10 were resistant to previous anthracycline and cytarabine therapy. Nine patients or 26%, with a 95% confidence interval (CI) ranging from 18-67%, achieved complete remission, including one patient at diagnosis (14%, CI: 0-58%), seven with relapsed AML (41%, CI: 18-67%), and one with resistant AML (10%, CI: 0-45%). Median durations of neutropenia below 0.5 x 10(9)/l and of thrombocytopenia below 20 x 10(9)/l were 24 and 20 days respectively. Severe toxicity included infections in 20 patients (59%), bleeding in two (6%), cardiac anomalies in two (6%), and vomiting in one (3%). Overall four patients (12%) died from chemotherapy related toxicity and 21 (62%) had resistant disease. Median overall survival was 4 months and median disease-free survival 8 months. We conclude that this regimen had efficacy with reduced toxicity in relapsed patients. Higher dosages for the same drugs could be tolerated by better risk patients for precise evaluation of cross reactivity with cytarabine-based regimens.

Acute Disease↗
PubMed1991

Follicular lymphomas: assessment of prognostic factors in 127 patients followed for 10 years.

Response to treatment, histologic progression, and survival of 127 patients with follicular lymphoma were analyzed according to histologic, clinical, and biological parameters. Histologic parameters were percentage of large cells (less than 10%, 41 patients; 10-25%, 38 patients; 25-50%, 11 patients; greater than or equal to 50%, 30 patients), percentage of diffuse areas, presence of intrafollicular proliferation or fibrosis, and mitotic scale. Eighty percent of the patients achieved complete remission (CR) with radiotherapy for localized stages and various chemotherapy regimens for disseminated stages. Three patients did not respond to treatment, and 23 were in partial remission (PR) at the end of treatment. Median survival time was 9.25 years. A constant death rate of 8% per year was observed without plateau. Histologic progression was observed in 32 patients; it occurred at a constant rate during the first six years and plateaued thereafter. Factors associated with low response rate were stage IV, B symptoms, high tumor mass, and two or more extranodal sites. Factors associated with histologic progression were bone marrow involvement and two or more extranodal sites. Factors associated with poor survival were advanced stage, two or more extranodal sites, bone marrow involvement, high lactate dehydrogenase level, and absence of interfollicular fibrosis. The percentages of large cells and diffuse areas had no influence on prognosis, nor had the type of treatment. Median survival has not been reached for CR patients and was four years for PR patients (P less than 0.0001). The LNH-84 prognostic index for aggressive lymphomas, based on tumor mass, number of extranodal sites, stage, and LDH level, is a clear-cut indicator of prognosis in follicular lymphomas too.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

v-erbA oncogene abrogates growth inhibition of chicken embryo fibroblasts induced by retinoic acid.

Retinoic acid inhibits chicken embryo fibroblast (CEF) proliferation by altering the G1 phase of the cell cycle with induction of a strong increase in the generation time. This growth-inhibitory response to retinoic acid is abrogated by expression of the v-erbA oncogene, suggesting an interference between retinoic acid receptors and the v-ErbA oncoprotein. Moreover, CEF expressing either the v-src, v-jun or v-fos oncogenes are also insensitive to retinoic acid treatment. In contrast, CEF expressing either the v-myc, v-myb-ets, v-mil, v-sea or v-erbB oncogenes are still sensitive to retinoic acid. These data strongly suggest functional interferences between the retinoic acid receptors and the AP-1 transcription factor complex in the control of expression of genes involved in CEF proliferation.

Animals↗
PubMed1990

Break in the BCL1 locus is closely associated with intermediate lymphocytic lymphoma subtype.

The t(11;14)(q13;q32) is a recurring translocation associated with some chronic B-cell lymphocytic malignancies; the putative protooncogene BCL1, located at the chromosome band 11q13, can be involved during the translocation process. In order to determine if BCL1 rearrangement is associated with a particular subtype of lymphoma, we analysed 131 B-cell non-Hodgkin's lymphoma samples by Southern blot analysis, using a BCL1 probe. The BCL1 locus was rearranged in 9 out of 25 (36%) cases of intermediate lymphocytic cell lymphomas (ILL), in 1 out of 8 cases of diffuse small cleaved cell lymphoma, in 1 out of 12 cases of diffuse mixed cell lymphoma, and in 1 out of 21 cases of diffuse large cell lymphoma. In contrast, BCL1 was never found rearranged in any of the 46 follicular lymphomas analysed. The BCL2 gene was in germ-line configuration in all ILL. Sequential hybridization of Southern blots with JH, C mu, and BCLI probes identified comigrating fragments in only one case of ILL, which suggests that, in all the other cases, either the rearrangement of BCL1 did not result from a t(11;14) translocation or the break on chromosome 14 occurred outside the JH or C mu regions. These results indicate that rearrangement of the BCL1 locus may be closely associated with ILL and could be considered as a genotypic marker of this lymphoma subtype.

Blotting, Southern↗
PubMed1990

Circulating levels of osteonectin in normal subjects and patients with thrombocytopenia.

In order to clarify the relative contributions of activated platelets and other sources to circulating osteonectin, the amounts of osteonectin present in serum and in plasma prepared without significant platelet activation were compared to platelet count in normal subjects and patients with various degrees of thrombocytopenia. Serum osteonectin showed a logarithmic positive correlation with platelet count (r = 0.87, P less than 0.0001, n = 52). Osteonectin concentration was significantly lower in plasma than in matched sera in all subjects sampled, and not significantly different in plasma of thrombocytopenic and normal subjects. These results confirm the major contribution of platelets to serum osteonectin. The positive zero intercept of the plot osteonectin vs. platelet count (19 +/- 2.45 ng/ml, mean +/- SD, P less than 0.0001, n = 52) and the presence of significant amounts of osteonectin in plasma, document the existence of a basic level of circulating osteonectin, independent of platelet activation, and to which the relative contribution of bone remains to be assessed.

Adult↗
PubMed1990

Is there an accumulation of cells during G2 in some acute lymphoblastic leukaemias?

In some cases of acute lymphoblastic leukaemia (ALL) the percentage of cells in G2 + M is higher than anticipated when compared with the percentage in S phase. This increase in G2 + M, as detected by flow cytometry measurement of DNA content, may be due to an accumulation of cells, either in G2 or during the end of S phase; it may also be related to the existence of small tetraploid clones generally ignored by cytogeneticists. In order to identify possible subpopulations of cells with a DNA index greater than or equal to 2.0, we have compared the results of a cytogenetic analysis to the G2 + M values. We have also studied the distribution of S phase cells in 24 cases of ALL by incorporating 5-bromodeoxyuridine, labelling the cells by indirect immunofluorescence, and analysing them by flow cytometry after propidium iodide staining. The distribution of cells during S phase was quantified: no accumulation of cells was ever observed at the end of S phase. The question of the existence of small tetraploid clones, G2 arrested cells or cells with a G2 elongation remains open. However, we feel that it is more probable that, in this pathology, an elongation of the duration of G2 occurs.

Adolescent↗
PubMed1990

Determination of plasma cell labelling index with bromodeoxyuridine using a double immunoenzymatic technique.

Myeloma plasma cells were double stained using peroxidase and alkaline phosphatase labelled monoclonal anti-BrdU and anti-intracytoplasmic immunoglobulins. Samples were methanol fixed; DNA was denatured with formamide. The results allowed easy identification of plasma cells, their cytological examination and the calculation of percentage of plasma cells in S phase. Good correlation was found with the labelling index obtained with tritiated thymidine.

Bromodeoxyuridine↗
PubMed1990

Myeloid differentiation antigens identify leukemic cell subpopulations with different cell cycle characteristics.

In order to assess the proliferative capacity of leukemic subpopulations and to know whether it can be related to the stage of maturation, the expression of two surface antigens identifying distinct steps of leukocyte differentiation (CD15 and CD34) was studied by flow cytometry in correlation with DNA content in 16 cases of acute myeloid leukemia (AML). The surface markers were studied by indirect immunofluorescence, using the monoclonal antibodies VIMD5 (anti-CD15) and MY10 (anti-CD34). The percentage of cells stained by each antibody and the intensity of staining were heterogeneous. Double-staining showed that a small percentage of cells coexpressed both antigens. A correlation was found between the percentage of cells stained by MY10 and the percentage of cells in S + G2 + M in the whole population (p less than 0.05). The percentage of cells in S + G2 + M was significantly higher in MY10-positive than in MY10-negative cells (p less than 0.005), and also higher in VIMD5-positive than in VIMD5-negative cells (p less than 0.005). In the 14 cases expressing both antigens, the percentage of cells in S + G2 + M was higher in VIMD5-positive than in MY10-positive cells (p less than 0.05), whereas there was no difference between VIMD5-negative and MY10-negative cells. It is concluded that the phenotype heterogeneity observed in leukemic cell populations is associated with differences in proliferative capacities. The subset of leukemic cells with the more mature phenotype (CD15-positive) has the highest proliferative activity.

Antigens, CD↗
PubMed1989

Cell kinetics in acute lymphoblastic leukaemia: comparative analysis between adults and children.

Cell kinetics were studied in 124 patients with acute lymphoblastic leukaemia (ALL) by flow cytometry, comparing cell cycle characteristics between adults (57 cases) and children (67 cases). S, G2 + M and the low protein content fraction of G1 (LPC fraction) were determined and studied in relation to other clinical and biological features. No difference was found between adults and children in the distribution of these variables. The proliferative rates according to organomegaly, leukocytosis, the FAB cytological groups and the immunological groups did not present any significant differences between the two groups of patients. However, cell cycle did seem to have a very different prognostic value for adults and for children. G2 + M was a strong prognostic indicator for childhood ALL: duration of CR and survival were significantly longer when G2 + M was higher (P less than 0.01). In adults, survival was longer for intermediary (between 3.8 and 5.8%) and high (over 7.2%) G2 + M values (P less than 0.01). The negative correlation between S and G2 + M observed in adults and the absence of correlation in children raise the possibility of differences in duration of the different phases for the two groups and perhaps an accumulation of cells in G2 or tetraploidy in some cases.

Adolescent↗
PubMed1989

Double immunocytochemical labeling of cell and tissue samples with monoclonal anti-bromodeoxyuridine.

We describe a new monoclonal antibody (designated Bu20a) against bromodeoxyuridine (BrdU). This antibody was selected by screening against human tissues using the APAAP technique, and shows no crossreactivity with normal nuclei. It stains BrdU incorporated into the nuclei of a wide range of cell types, including human tonsil lymphoid cells, normal mouse tissues, and human tumors growing in nude mice. A double-labeling technique is described using this antibody in which cell smears or tissue sections are first labeled by an immunoperoxidase procedure for a cellular antigen (e.g., mouse or human histocompatibility class II antigen, T-lymphocyte antigen, keratin) and BrdU is then detected by indirect immunofluorescence. This procedure, which was applied to a variety of human and animal cells and tissues, is of wide potential value in analyzing the phenotype of S-phase cells and in co-localizing antigen expression and BrdU incorporation in tissue sections.

Animals↗
PubMed1989

DNA assessment in thin sections of lymphomas by densitometric and stereological methods: comparison with imprint and flow cytometric results.

The nuclear DNA content was estimated in 2 microns sections of 18 lymphoma cases by two methods: (1) Feulgen densitometry using QTM 900 with correction by Bins' procedure which allows size-independent DNA distributions; (2) stereological unfolding as proposed by Cruz-Orive giving sphere-size distributions. A general correlation was found between results and DNA measurements obtained by imprint and flow cytometric techniques in the same specimens. When histologic DNA profiles were compared to cytologic histograms, a high correlation was found between the distribution of ploidy classes by correspondence analysis. However two highly proliferating lymphomas were erroneously classified as aneuploid. Conversely, sphere-size distributions allowed the identification of the majority of aneuploid lymphomas but failed to recognize proliferating ones. It appears that when cytologic specimens are not available, densitometric studies on sections may provide valuable information on DNA content, with complementary data obtained from stereological procedures.

Aneuploidy↗
PubMed1988

Image analysis applied to proliferating cells in malignant lymphoma.

This study describes a method for obtaining the distribution of a given cell type in histological sections, as revealed by a specific immunological marker. Two hundred fifty-six contiguous microscopic fields were analysed, and a cellular map was automatically constructed. The resulting images were stored on magnetic media for subsequent quantification and statistical tests. The method was applied to the analysis of 20 small cleaved-cell lymphomas in which the monoclonal antibody Ki-67 was used to mark proliferating cells. Clusters of proliferative cells were observed in both diffuse and nodular lymphomas. Cellularity and the percentage of marked cells were not significantly different in the two types of tumors.

Antibodies, Monoclonal↗
PubMed1988

The syndrome of abnormal chromatin clumping in leucocytes: a myelodysplastic disorder with proliferative features?

Five patients presenting extremely exaggerated chromatin clumping in leucocytes, associated with a loss of segmentation, are described. Peripheral cytopenia, a high percentage of circulating immature granulocytes (chiefly myelocytes) with variable leucocytosis, marrow hypercellularity with granulocytic hyperplasia and moderate dysplastic changes in erythroblastic and megakaryocytic lines, constitute, together with the granulocytic nuclear anomaly, the characteristic features of the studied cases. Cytogenetic analysis showed a clonal 12p anomaly in one of the three cases available for study. Survival was poor with a median of 15 months, bleeding and infections being responsible for the majority of deaths. All these findings point to abnormal chromatin clumping in leucocytes as the marker of a true entity with both myelodysplastic and myeloproliferative features. We propose that it take its place among myelodysplastic syndromes (MDS) beside chronic myelomonocytic leukaemia (CMML), with which it shares many similarities in clinical and biological behaviour.

Aged↗
PubMed1988

B-cell acute lymphoblastic leukaemia: clinical and biological aspects.

Acute lymphoblastic leukaemia of B-cell phenotype (B-ALL) is uncommon. We studied eight cases of B-ALL, investigating the clinical characteristics as well as the biological features. Cytology revealed a typical L3 profile in most cases, but in one case the morphological diagnosis was L2 and morphometric analysis indicated that the blasts in B-ALL were larger than in other ALLs. Cytogenetic study detected the typical translocations (8; 14) and (8; 22) in most of the cases. Abnormalities of the long arm of the chromosome 1 were found in four cases and a major aneuploidy was observed in one case. Cell-cycle analysis showed a high degree of proliferation with, in all cases, a small fraction of cells in G1 with low protein content (corresponding to early G1). All these biological characteristics must be related to the poor prognosis of this disease.

Acute Disease↗
PubMed1988

DNA, RNA, and protein content in adult acute myeloid leukemia: effects of cytostatic drugs in vivo.

DNA, RNA, and/or protein cellular content were studied by flow cytometry in 52 cases of acute myeloid leukemia before and on day 4 of remission induction treatment. Bone marrow (BM) samples were stained after fixation by acridine orange for DNA and RNA content (37 cases) and by propidium iodide and fluorescein isothiocyanate for DNA and protein content (52 cases). A positive correlation was found between pretreatment protein content and BM blast involvement: the higher the percentage of blasts in BM smears the higher the mean protein content (p less than 0.05). Protein content was higher in monoblastic leukemia (M4 and M5) than in the granulocytic types (M1, M2, M3) (p less than 0.05). S + G2 + M was higher in patients with protein content below 80 arbitrary units than in the subgroup with protein content above this threshold (p less than 0.05). Pretreatment RNA content, estimated by the RNase-sensitive fraction of G1 cells, was significantly higher in undifferentiated and M1 leukemias than in the other cytological groups (p less than 0.0001). This fraction was higher in patients who subsequently achieved complete remission, but it was not related to BM blast involvement or proliferative fraction of cells. During cytostatic treatment the changes in RNA and protein content did not follow a typical pattern. The connections between variations of DNA, RNA, and protein content and prognosis are examined and their possible relation to drug-induced blast cell maturation is discussed.

Acridine Orange↗