PubMed Health⌕ Search

Biomedical subjects

T Lamy

Publications and source records attributed to T Lamy.

At least 37 records · Page 2Linked to original sources
PubMed1999

Current concepts: large granular lymphocyte leukemia.

Clonal diseases of large granular lymphocyte (LGL) disorders can arise from a CD3+ T-cell lineage or from a CD3- NK-cell lineage. CD3+ LGL leukemia is the most frequent form of LGL leukemia. T-LGL leukemia usually affects elderly people. Approximately 60% of patients are symptomatic; recurrent infections secondary to chonic neutropenia, anemia, and rheumatoid arthrititis are the main clinical manifestations. The most common phenotype is CD3+, alphabeta+, CD8+, CD57+. Clonality is detected by clonal rearrangement of the T-cell receptor gene. NK-cell LGL proliferative disorders include NK LGL leukemia which is a very aggressive disease and NK chronic lymphocytosis. Serologic findings show frequent reactivity to the BA21 epitope of HTLV-I env p21e, suggesting that a cellular or retroviral protein with homology to BA21 may be important in pathogenesis of these diseases. Clonal expansion may be facilitated by IL12 and IL15 cytokines expressed by leukemic LGL, and also by a defective Fas (CD95) apoptotic pathway. Leukemic LGL constitutively express Fas and Fas-Ligand but they are resistant to Fas-induced apotosis. Neutropenia could be due to soluble Fas-Ligand which is highly secreted in the patient's sera. Clinical and molecular remission can be obtained with oral low-dose methotrexate. Leukemic LGL express a multi-drug resistance phenotype (PgP+/LRP+) that could partly explain the chemoresistance observed in aggressive cases. It is suggested that LGL leukemia can serve as a useful model of dysregulated apoptosis as an underlying mechanism for both malignancy and autoimmune disease.

Autoimmune Diseases↗
PubMed1998

Dysregulation of CD95/CD95 ligand-apoptotic pathway in CD3(+) large granular lymphocyte leukemia.

CD95 (Fas)-induced apoptosis plays a critical role in the elimination of activated lymphocytes and induction of peripheral tolerance. Defects in CD95/CD95L (Fas-Ligand)-apoptotic pathway have been recognized in autoimmune lymphoproliferative diseases (ALPS) and lpr or gld mice and attributed to CD95 and CD95L gene mutations, respectively. Large granular lymphocyte (LGL) leukemia is a chronic disease characterized by a proliferation of antigen-activated cytotoxic T lymphocytes. Autoimmune features such as hypergammaglobulinemia, rheumatoid factor, and circulating immune complexes are common features in LGL leukemia and ALPS. Therefore, we hypothesize that expansion of leukemic LGL may be secondary to a defective CD95 apoptotic pathway. In this study, we investigated expression of CD95 and CD95L in 11 patients with CD3(+) LGL leukemia and explored the apoptotic response to agonistic CD95 monoclonal antibody (MoAb). We found that leukemic LGL from each patient expressed constitutively high levels of CD95/CD95L, similar to those seen in normal activated T cells. However, cells from 9 of these 11 patients were totally resistant to anti-CD95-induced apoptosis. Similarly, cells were resistant to anti-CD3-MoAb-triggered cell death. Lack of anti-CD95-induced apoptosis was not due to mutations in the CD95 antigen. Leukemic LGL were not intrinsically resistant to CD95-dependent death, because LGL from all but 1 patient underwent apoptosis after phytohemagglutinin/interleukin-2 activation. The patient whose leukemic LGL were intrinsically resistant to CD95 had an aggressive form of LGL leukemia that was resistant to combination chemotherapy. These findings that leukemic LGL are resistant to CD95-dependent apoptosis despite expressing high levels of CD95 are similar to observations made in CD95L transgenic mice. These data suggest that LGL leukemia may be a useful model of dysregulated apoptosis causing human malignancy and autoimmune disease.

Adult↗
PubMed1998

Early intensive therapy with autologous stem cell transplantation in advanced Hodgkin's disease: retrospective analysis of 158 cases from the French registry.

This retrospective study was undertaken to evaluate cure rates, toxicity and late effects of early intensive therapy followed by autologous stem cell transplantation (ASCT) in patients with advanced Hodgkin's disease (HD). One hundred and fifty-eight cases of ASCT registered in the French database (SFGM) were retrospectively analyzed. Disease status at the time of ASCT was first partial response (PR) in 85, first complete remission (CR1) in 45 or primary refractory in 28 cases. The median time interval between diagnosis and ASCT was 7 months (range 4-13). At the time of analysis in December 1995, 121/158 patients (76.6%) were alive, including 111 (70.2%) in continuous CR with a median follow-up for surviving patients of 46 months (range 8-123). Peri-ASCT toxic death rate was 3%, and the actuarial risk of new malignancies was 4.9% at 5 years. The cumulative probability of 5-year overall survival (OS) was 75.2% for the entire group of patients, 80.6% for the chemosensitive ones, and 33.9% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The cumulative probability of 5-year event-free survival (EFS) was 66.1% for the entire group of patients, 73.7% for the chemosensitive ones, and 26.1% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The only significant prognostic factor for both OS and EFS was disease status at the time of ASCT. Early ASCT in advanced HD is feasible, with a low risk of toxicity and without a higher rate of late effects compared with conventional treatment. Results achieved in chemosensitive patients at the time of transplantation lay the basis of future prospective randomized trials comparing ACST as front-line treatment to conventional treatment in high-risk cases.

Adolescent↗
PubMed1998

Multidrug resistance analysis in lymphoproliferative disease of large granular lymphocytes.

Multi-drug resistance (MDR) phenotype contributes to the ineffectiveness of chemotherapy. P-glycoprotein (PgP) and lung resistance protein (LRP) are proteins implicated in chemoresistance. We analysed the expression of PgP and LRP respectively in 17 and 15 cases of lymphoproliferative disease of granular lymphocytes (LDGL) including 10 cases of clonal large granular lymphocytic (LGL) leukaemia, six cases of oligoclonal (n = 5) and polyclonal (n = 1) CD3+ lymphoproliferation and one case of CD3- NK lymphocytosis. Functional PgP activity, as determined by Rh123 dye efflux assay, was found in all the patients. The mean percentage of effluxing cells was 47 +/- 22%, compared to 35 +/- 8% on normal lymphocytes (P<0.04). The efflux was blocked in the presence of verapamil, a PgP revertant agent. A high proportion of CD57+ cells (66 +/- 10%) from these patients expelled Rh123. Functional PgP activity was associated with expression of MDR1 mRNA. By using immunocytochemistry, LRP expression was detected in 11/15 patients (73%). 7/10 LGL leukaemia patients presented a LRP+/Efflux+ phenotype and 5/7 had LRP+/Efflux+/MDR1 mRNA+ phenotype. These findings suggest that the PgP+/LRP+ phenotype is frequently observed in LDGL. Its clinical relevance in aggressive cases remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Loss of HLA molecules in B lymphomas is associated with an aggressive clinical course.

Major histocompatibility complex class I molecule expression is reduced in some malignant tumours permitting escape from immune surveillance and is therefore associated with a poor prognosis. Seven cases of non-Hodgkin lymphomas out of 300 cases of malignant lymphoproliferative disorders totally lacked expression of class I molecules as determined by flow cytometry. Clinical data confirmed a particular aggressiveness of these cases with frequent extra-nodal involvement, a poor international prognostic index, a histological high grade and a poor outcome leading to early death in five of the seven cases. A previous diagnosis of follicular lymphoma characterized by bcl-2 rearrangements was made in four of these cases. HLA-G (class Ib gene), which is reported to bind killer inhibitory receptors on NK cells, was absent from the cell surface. However, it was detected in three out of four cases at the mRNA level with transcripts encoding soluble forms. Additional analysis revealed other abnormalities: class II was negative in four out of the seven NHL cases and decreased expression of beta2 microglobulin was observed in all cases. Peptide transporter proteins (TAP1) were detected in various degrees by immunocytochemistry. These observations showed that total lack of class I or class II molecules is a rare event in NHL and is associated with a poor prognosis. This could support a role for specific autologous T cells in immune surveillance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Large Granular Lymphocyte Leukemia.

BACKGROUND: Clonal diseases of large granular lymphocyte (LGL) disorders can arise from a CD3+ T-cell lineage or from a CD3- NK-cell lineage. CD3+ LGL leukemia is the most frequent form of LGL leukemia and is a distinct entity by FAB and REAL classifications. METHODS: The clinical course, biological features, and recent data on pathogenesis of CD3+ LGL leukemia are reviewed. The spectrum of differential diagnosis is described. RESULTS: T-LGL leukemia affects elderly people. Approximately 60% of patients are symptomatic; recurrent infections secondary to chronic neutropenia, anemia, and rheumatoid arthritis are the main clinical features. The most common phenotype is CD3+, CD8+, CD57+. Clonality is detected by clonal rearrangement of the T-cell receptor gene. Clinical and molecular remission can be obtained with oral low-dose methotrexate. Serologic findings show frequent reactivity to the BA21 epitope of HTLV-I env p21e, suggesting that a cellular or retroviral protein with homology to BA21 may be important in pathogenesis. Clonal expansion may be facilitated by IL-12 and IL-15 lymphokines. Constitutive expression of Fas ligand by leukemic LGLs support the hypothesis that leukemic cells arise from antigen-activated cytotoxic T cells. Leukemic LGLs express a multidrug-resistance phenotype that could partly explain the chemoresistance observed in aggressive cases. CONCLUSIONS: CD3+ LGL leukemia is a distinct lymphoproliferative T-cell disorder with specific clinicobiological aspects. The clinical spectrum of LGL proliferations is wide and immunophenotypic, and genotypic studies are needed to establish the diagnosis.

Journal Article↗
PubMed1998

Prophylactic use of itraconazole for the prevention of invasive pulmonary aspergillosis in high risk neutropenic patients.

Invasive pulmonary aspergillosis (IPA) is an increasing cause of morbidity and mortality in patients with hematologic malignancies. A major program of construction work close to our unit prompted us to evaluate the efficacy of itraconazole prophylaxis in preventing IPA in these patients. During September 1994 to December 1995, 77 patients undergoing 96 neutropenic episodes (mean duration, 19.3 days +/- 9.1) received itraconazole as antifungal prophylaxis. All patients were treated in laminar air flow rooms. Itraconazole was administered at a loading dose of 600mg/d, (day 1 to day 3) and 400mg/d on the following days, in 87 instances. In the remaining episodes, the daily dose was 200 or 400mg. Oral doses were adjusted to reach a plasma itraconazole level (PIL) above 1000ng/l. In cases of inadequate PIL or poor oral intake, IV AmphoB was started at a 20 mg daily dose. Five cases of IPA (proven n = 2, probable n = 3) were observed. This represents an incidence of 5.2% of the total number of episodes. One out of 67 (2%) treatment episodes with adequate PIL were associated with IPA as compared to 4 of 29 (14%) episodes with inadequate PIL, (p < 0.02). AmphoB was added in 28 cases because of low PIL (n = 25), and/or antibiotic-resistant fever persistent pulmonary infiltrate (n = 8). These results need to be interpreted with caution, because of the absence of randomization or a control group. The efficacy of Itraconazole in neutropenic patients with high risk IPA has to be confirmed on larger and prospective studies.

Adult↗
PubMed1998

Multidrug resistance in aggressive lymphoproliferative disorders of T and natural-killer origin.

The measurement of rhodamine 123 (Rho123) efflux in hematological malignancies, using flow-cytometry, provides an accurate assessment of multidrug resistance (MDR) of both P-glycoprotein and MRP. While their normal counterparts display high levels of PgP and Rho123 efflux, we investigated the MDR status of marked T/NK proliferations. When diagnosed according to natural killer (NK) markers (CD16, CD56, CD57) 8 of nine NK lymphoproliferative disorders (LPD) were markedly positive (3 NK non Hodgkin's lymphomas (NHL), 1 NK lymphoproliferative disease of large granular lymphocytes (LGL), and 5 T/NK LGL). These results are in accordance with the observed response to chemotherapy in the treated cases. Mature T LPD (prolymphocytic leukemia (PLL), and NHL) cells gave varying results, as did cells from Sezary syndromes. Marked Rho123 efflux was detected in the two cases of T-PLL suggesting the expression of MRP as previously described. Immature T-lymphomas or leukemias (6 cases) were all negative. These data should be considered in relation to NK proliferations which clearly display an MDR phenotype and therefore raise the question, of the relevance of this phenotype in normal cells, and secondly of the negativity of immature T-LPD. The latter could indicate that MDR inhibitors may be superfluous in the initial treatment of acute lymphoblastic leukemia (ALL). Finally the resistance to treatment of T-ALL or mature T cells LPD invokes the importance of exploring other mechanisms of drug resistance such as the lung resistance related protein (LRP).

Antigens, CD↗
PubMed1997

Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.

Acute Disease↗
PubMed1997

CD3- CD56+ non-Hodgkin's lymphomas with an aggressive behavior related to multidrug resistance.

CD56 expression has been reported previously in some non-Hodgkin's lymphoma (NHL) characterization. They principally involve the nasopharynx, are related to Epstein-Barr virus (EBV), and may be classified as either T- or non-T-natural killer (NK) cells according to CD3/T-cell receptor (TCR) status at the genomic or protein level. The present study reports three cases of non-nasal NK-NHL with the following characteristics: an agressive clinical behavior, heterogenous morphological data evoking pleomorphic T-cell malignant lymphoma, a non-T-NK phenotype using flow cytometry, and immunochemistry. The three cases were CD56+ without membrane expression of specific T markers (CD3, CD5, and TCR). Heterogenous results were observed concerning different antigens: CD2, CD4, CD8, CD16, CD94, CD122, TiA1, perforin, and granzyme B. There was no evidence of detectable clonal TCR gene rearrangement with polymerase chain reaction. No NK activity was detected in the two tested cases, and no relation was found with EBV. Multidrug resistance investigations suggest that agressive clinical findings could be related to MDR1 gene expression as confirmed by MDR1 mRNA detection, MDR1 gene product (Pgp) expression, and a functional multidrug resistance study using rhodamine efflux by flow-cytometry.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Inapparent polycythemia vera: an unrecognized diagnosis.

PURPOSE: The Polycythemia Vera Study Group (PVSG) has established useful criteria for the diagnosis of polycythemia vera. In some circumstances, an increase of plasma volume (PV) masks that of red cell mass (RCM), with hemoglobin (Hb) and hematocrit (Ht) remaining normal. This defines the concept of inapparent polycythemia. PATIENTS AND METHODS: One hundred and three patients seen in the hematology unit with the diagnosis of polycythemia vera were studied. There were 55 males and 48 females with a median age of 59 years. Ninety-five patients fulfilled the PVSG criteria. Spontaneous erythroid colonies and low serum erythropoietin level confirmed the diagnosis in the 8 other cases. Patients were classified according to Hb and Ht level. RESULTS: Group A consisted of 85 patients with increased Hb and Ht defined, respectively, by Hb > 18 g/dl, Ht > 0.52 in males and Hb > 16 g/dL, Ht>0.47 in females. Group B included 18 patients (17%) with inapparent polycythemia vera (IPV) defined by a normal Hb and Ht value at diagnosis. In this group, the reasons to perform RCM were as follows: splenomegaly associated with increased platelets and/or leucocytes counts (n = 8), portal vein thrombosis (n = 5), increased platelets or leucocytes counts without splenomegaly (n = 3), and isolated splenomegaly (n = 2). The two groups were balanced in terms of age, sex, leucocyte, serum iron, and platelet level. Hemoglobin and Ht levels were significantly different between the two groups. The difference between the PV was indeed highly significant. The mean PV increase was + 9.5% (nL < +20%) in group A versus + 36.3% in group B (P < 0.00005). Red cell mass was not different between the two groups. CONCLUSIONS: Increased Hb or Ht should constitute the sole criteria for RCM determination. In the context of portal vein thrombosis, isolated hyperleucocytosis, thrombocytosis, or splenomegaly, a RCM should be performed. The frequency of IPV remains to be specified but the diagnosis of polycythemia vera is probably underestimated.

Adult↗
PubMed1997

Is the International Prognostic Index for aggressive lymphomas useful for low-grade lymphoma patients? Applicability to stage III-IV patients. The GOELAMS Group, France.

BACKGROUND: The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma. PATIENTS AND METHODS: One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4). RESULTS: Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P < 0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months. CONCLUSIONS: In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

Humans↗
PubMed1996

Inhibition of P-glycoprotein activity in human leukemic cells by mifepristone.

The antiprogestatin drug mifepristone has previously been shown to potentiate anti-cancer drug activity in rodent multidrug-resistant cell lines through inhibition of P-glycoprotein (P-gp) function. In order to characterize P-gp-mifepristone interactions in human tumoral cells, we have studied the effect of the antiprogestatin agent on P-gp activity in human CD34+ leukemic cells known to display high levels of P-gp-related drug efflux. P-gp-mediated transport of the fluorescent dye rhodamine 123 occurring in the CD34+ KG1a myeloid leukemia cell line was found to be strongly inhibited by mifepristone in a dose-dependent manner. Similarly to verapamil, a well-known chemosensitizer agent, the antiprogestatin drug increased doxorubicin cytotoxicity in KG1a cells. Mifepristone, when used at a 10 microM concentration thought to be achievable in vivo without major toxicity, was also able to markedly decrease cellular rhodamine 123 efflux occurring in CD34+ blast cells isolated from six patients suffering from myeloid acute leukemias. These results thus indicate that mifepristone can strongly inhibit P-gp activity in human cells, including tumoral cells freshly isolated from patients, therefore suggesting that the clinical use of this compound may contribute to down-modulate P-gp-mediated drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Distribution of HLA-G alternative mRNAs including soluble forms in normal lymphocytes and in lymphoid cell-derived leukemia.

The non-classical HLA-G gene is the only class I antigen expressed in trophoblasts at the maternofetal interface. In placenta, the HLA-G gene produces several alternatively spliced isoforms encoding bound-membrane proteins (G1, G2, G3 and G4) lacking, respectively, exon 7; exons 7 and 3; exons 7, 3 and 4, and exons 7 and 4. In addition, two isoforms (G1s and G2s) containing an intron 4 sequence are able to encode soluble antigens. We have recently reported that the HLA-G gene is transcriptionally active in lymphocytes and is not transcribed in CD34+ cells, polynuclear cells or monocytes. To investigate the functional significance of the different isoforms in lymphocytes, we studied their distribution in normal T and B lymphocytes and in malignant lymphoid cells by using the RT-PCR technique followed by hybridization with exon-specific probes and sequencing assays. In transcriptionally active lymphocytes, the HLA-G primary transcript is the major form and is differentially spliced in B and T lymphocytes: (i) G1s is found in several samples of T and B cells whereas G2s is only transcribed in T lymphocytes, (ii) the G4 isoform is never detected in B lymphocytes. In addition, we have shown that HLA-G is inactive in some samples of lymphocytes. Our data suggest that HLA-G transcription is regulated at the initiation level and at the subsequent splicing. These two levels of regulation may be dysregulated in some cases of T-ALL and CLL. The potential functions of the HLA-G alternative forms in lymphocytes, such as peptide binding and modulation of the immune response, are discussed.

Alternative Splicing↗
PubMed1996

Idarubicin and high dose cytarabine: a new salvage treatment for refractory or relapsing non-Hodgkin's lymphoma.

Twenty three patients with relapsing (n = 11) or refractory (n = 12) non-Hodgkin's lymphoma (NHL) to one or two prior anthracycline based combination chemotherapy regimens were treated as second or third line regimen with 3 induction cycles of Idarubicin (IDA) (7 mg/m2/d i.v. d1-d3) and high dose cytarabine (HD Ara-C) (1 g/m2/12 h i.v. d1-d3), each cycle was repeated every 3 weeks. Responding patients received a maintenance therapy with monthly cycles of IDA: 15 mg/m2 d1-d3, Etoposide 100 mg/m2 d1-d3, both by oral route. Twenty two patients are evaluable and we observed 13 CR and 1 PR with an overall response rate of 61% (14/23: 95% Cl = 38.5% 80.3%). The median time to progression was 32 months (6.5 - 63 + m.). The response rate to IDA-HD Ara C was not different for patients with (n = 14) or without (n = 9) objective response to the last prior therapy. The main toxicity was hematological: all patients experienced grade 4 neutropenia and 22 patients had grade 4 thrombopenia, but there were no toxic deaths. IDA and HD-Ara-C combination is highly effective in refractory or relapsed. NHL. As hematological toxicity was the limiting factor for further escalation of dose-intensity, further studies might include hematopoietic growth factors support in the therapeutic scheme.

Adult↗
PubMed1996

Multifactorial drug-resistance phenomenon in acute leukemias: impact of P170-MDR1, LRP56 protein, glutathione-transferases and metallothionein systems on clinical outcome.

The multidrug resistance phenomenon can be observed in cases which do not express the P170 protein and these cases are suspected as having activated different resistance phenomena. Four phenomena were studied at the time of diagnosis in a series of 35 lymphoblastic and 25 myeloblastic acute (de novo) leukemias, by an immunocytochemical method. Two energetic drug transport processes were investigated: the classical MDR/P170 and the P110/LRP56 proteins, and two physiological detoxifying activities such as the glutathione transferases (GST alpha, mu, pi) and the metallothioneins (Mts). The results demonstrate that these phenomena are independent but their synergic activity can increase their impact on the outcome. P110/LRP56 positive cases demonstrated 48.8% complete remission (CR) rate compared to 71.4% for negative tests. When P170 and P110 were both positive or negative, the CR rates were 27.3% and 81.8% respectively (p = 0.0120), and survival curves were also different (p = 0.030). The CR rate in AML or ALL is weakly affected by GST pi, alpha or mu but relapses are more frequently observed for Positive-GST pi ALL (p = 0.0658). Patients with both P170 and GST pi positive reactions had a 53.3% CR rate compared to 78.9% for both negative reactions. Survival curves for these two groups were different. The CR rate in AMl was 100% for Mts positive and 43.7% for negative cases (p = 0.050), however the median survival was totally different for these two groups (p = 0.046). CR rates were 26.6% for patients who were P170 positive and Mts negative compared to 100% for P170 negative and Mts positive (p = 0.038) patients. Survival curves were also different (p = 0.0510). We conclude that these four mechanisms induce an independent drug resistance but their synergic action increase their impact on the outcome. The metallothioneins seem to have a major impact on the drug resistance phenomenon and its effect should be investigated with high priority, in the light of these results.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Epidemiologic analysis of glycopeptide-resistant Enterococcus strains in neutropenic patients receiving prolonged vancomycin administration.

Vancomycin-resistant enterococci have been isolated with increasing frequency since 1988. Thus far, most of these resistant enterococci have belonged to the Enterococcus faecium species, and epidemiological studies have shown a wide diversity among interhospital and intrahospital isolates. This report presents an epidemiologic investigation of 25 vancomycin-resistant Enterococcus strains--24 Enterococcus faecium and one Enterococcus gallinarum--isolated from the stools or blood of adult patients receiving intravenous vancomycin prophylaxis during neutropenia and hospitalized in a single hematologic unit. Macrorestriction patterns of total DNA and of ribosomal DNA regions were used to analyze the strains. Strains produced different total DNA restriction fragment length polymorphism patterns after SmaI digestion. Ribotyping was less discriminative than pulsed-field gel electrophoresis. The results confirmed the genetic unrelatedness of the strains. Prolonged vancomycin administration, commonly used in hematologic units, could be involved in the selection of endogenous resistant enterococcal strains.

Anti-Bacterial Agents↗