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G Salles

Publications and source records attributed to G Salles.

At least 19 recordsLinked to original sources
PubMed1998

Genetic polymorphisms in the tumor necrosis factor locus influence non-Hodgkin's lymphoma outcome.

Systemic release of tumor necrosis factor (TNF) and lymphotoxin-alpha (LTalpha) has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We investigated whether genetic polymorphisms in the TNF locus, previously shown to influence TNF and LTalpha genes expression, might contribute to these cytokines production and to the clinical course of NHL. Genomic DNA from 273 lymphoma patients was typed for TNF (-308) polymorphism using an allele-specific polymerase chain reaction (PCR) and for LTalpha (+252) polymorphism with a PCR-based restriction fragment length polymorphism. The presence of the TNF allele involved in increased TNF gene transcription was associated with higher plasma levels of this cytokine at the time of lymphoma diagnosis (chi2 test, P = .013). An extended haplotype analysis showed that the presence of at least two TNF or LTalpha high-producer alleles constituted a risk factor for first-line treatment failure (chi2 test, P = .021), shorter progression-free survival (log-rank test, P = .0007), and overall survival (log-rank test, P = .012). In the subgroup of 126 patients with diffuse large-cell lymphoma, the presence of two or more TNF/LTalpha high producing alleles contributed significantly to a higher rate of relapse and progression (log-rank test, P = .045 and P = .027). In multivariate Cox regression models including the variables of the International Prognostic Index, the TNF/LTalpha haplotype status was found to be an independent risk factor for progression-free survival (relative risk 2.33, 95% confidence interval [1.17 to 4.64], P = . 0053) and overall survival (relative risk 1.92, 95% confidence interval [0.63 to 5.80], P = .081) of large-cell lymphoma patients. These results indicate that genetic polymorphism leading to increased TNF production influences the outcome of NHL and suggest a pathophysiological role for the genetic control of the immune response in lymphoid malignancies.

Adult↗
PubMed1998

High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral blood progenitor cell transplantation.

Optimal numbers of CD34(+) cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34(+) cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 x 10(9)/L) and unsustained platelet recovery (>50 x 10(9)/L) were analyzed in three groups defined by the number of CD34(+) cells reinfused: a low group with less than or equal to 2.5 x 10(6) CD34(+) cells/kg, a high group with greater than 15 x 10(6) CD34(+) cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P < .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34(+) cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 x 10(6) CD34(+) cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.

Adolescent↗
PubMed1998

A new death receptor 3 isoform: expression in human lymphoid cell lines and non-Hodgkin's lymphomas.

Two isoforms encoding the full-length transmembrane death receptor 3 (DR3) were isolated from mRNAs of a panel of human cell lines and tumor tissues obtained from patients with follicular non-Hodgkin's lymphoma. A new DR3 variant (DR3 beta) was characterized by 2 insertions of respectively 20- and 7-base pairs (bp) which result in a predictive translated polypeptide differing from the described DR3 molecule by a 28 amino-acid stretch in the extracellular domain. DR3 was shown to be expressed in all cell lines and lymphoma samples tested, whereas DR3 beta expression was restricted to lymphoid T-cell and immature B-cell lines and to selected cases with follicular lymphoma. These data provide new insight into the molecular heterogeneity of DR3, suggesting the presence of several receptor isoforms that can participate in lymphoid cell homeostasis.

Base Sequence↗
PubMed1998

Plasma levels of tumour necrosis factor and its soluble receptors correlate with clinical features and outcome of Hodgkin's disease patients.

A prospective study was performed to assess the use of plasma measurement of tumour necrosis factor (TNF), lymphotoxin alpha (LT alpha) and their soluble receptors (p55 and p75) for prognostic risk assignment in 61 patients with Hodgkin's disease. Plasma levels of TNF, p55 and p75, but not of LT alpha, were higher in Hodgkin's disease patients than in healthy controls. Plasma levels of TNF, p55 and p75 were associated with several prognostic factors for Hodgkin's disease, including those related to the host (age, performance status) and to the tumour (disease stage, extranodal site involvement, bulky tumour, serum levels of LDH and beta2-microglobulin, histology). Elevated plasma levels of TNF, p55 and p75 were also associated with several parameters reflecting an immune activation, including the presence of B symptoms, elevated serum levels of gammaglobulins, alkaline phosphatase and fibrinogen, as well as peripheral monocytosis, anaemia and low serum albumin levels. Finally, elevated TNF ligand receptor plasma markers were associated with a lower incidence of complete response to therapy and predicted shorter free-from-progression survival and overall survival of the patients. These results indicate that the plasma levels of TNF and its soluble receptors correlate with clinical features and outcome of patients with Hodgkin's disease.

Adolescent↗
PubMed1998

Reduced progression-free survival in elderly patients receiving intensification with autologous peripheral blood stem cell reinfusion for multiple myeloma.

Between 1990 and 1997, 55 patients with high risk multiple myeloma underwent high-dose therapy with peripheral blood stem cell transplantation. Intensification consisted of high-dose L-PAM in 54 patients, and 15 patients underwent a second high-dose treatment. Thirty patients received total body irradiation. Twenty patients were more than 60 years old. Thirty-five patients were intensified during first response. The overall response rate was 78%. There were four toxic deaths. The median overall survivals after intensification and after first treatment of myeloma were greater than 48 months and 71 months, respectively. Conversely freedom from progression after intensification was short, with a median of 22 months. Freedom from progression was significantly shorter in patients older than 60 (12 months), and in patients who had received more than 75 mg/m2 of L-PAM before intensification (16 months). Although intensification is feasible in elderly patients the benefit appears to be reduced in this subgroup of patients. Prior therapy with high cumulative doses of L-PAM should be avoided in patients who will receive high-dose L-PAM for therapeutic intensification.

Adult↗
PubMed1998

The tumor necrosis factor signaling complex: choosing a path toward cell death or cell proliferation.

Signal transduction pathways which are initiated by the tumor necrosis factor (TNF) utilize receptors which are devoid of intrinsic catalytic activity. Recently identified two families of proteins that directly associate with the cytoplasmic domains of the TNF receptor family members, have partially bridged a molecular gap within the TNF-induced signaling pathways. Clearly, there are numerous alternate routes that originate from the TNF ligand-receptor assembly and terminate on the diverse cellular responses, including proliferation, differentiation, or death. This review focuses on recent advances characterizing the TNF ligand-receptor signaling network, which allow to better understand its participation in a life-death balance within the target cell.

Apoptosis↗
PubMed1997

Identification of two lymphotoxin beta isoforms expressed in human lymphoid cell lines and non-Hodgkin's lymphomas.

Two isoforms of lymphotoxin beta (LTbeta) were isolated from mRNAs of a panel of human lymphoid cell lines and tumor tissues obtained from patients with non-Hodgkin's lymphoma (NHL). The truncated LTbeta mRNA variant lacked 46 base pairs complementary to the complete sequence of exon 2, suggesting that both isoforms are produced by an alternative splicing mechanism. Skipping out of exon 2 causes a reading frame shift and a premature stop codon in the LTbeta mRNA variant. The predictive translated polypeptide would correspond to a severely shortened LTbeta protein that would lack the majority of the extracellular domain of the native molecule, thus impairing its normal complex assembly with LTalpha. These observations provide new insights into the molecular heterogeneity and biological function of LTbeta within the tumor necrosis factor and LT ligand-receptor system.

Base Sequence↗
PubMed1997

Intensive therapy with peripheral stem cell transplantation in 16 patients with mantle cell lymphoma.

BACKGROUND: Despite improved detection of mantle cell lymphoma (MCL), results of its treatment with conventional therapies remain disappointing and the survival rate poor. The role of high-dose chemotherapy has recently been investigated but no potential benefit has been clearly established. We report here our experience with MCL patients treated with intensive chemotherapy and autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Of the 16 MCL patients who received high-dose chemotherapy and ASCT beginning in 1989, six were treated in first-line and 10 in sensitive relapse. Twelve of 16 patients received regimens which included total body irradiation. All patients received peripheral blood stem cells (PBSC) with the exception of one, who underwent bone marrow transplantation. RESULTS: Three patients died of toxic effects of treatment, Three months after transplant, seven achieved complete response, (CR) and two partial responses (PR), two were stable and two had progressed. With a median follow-up after transplant of 22 months, five of the six surviving patients were without progression, and three were in CR. The median times for event-free survival (EFS) and overall survival (OS) were, respectively, 249 and 317 days. The expected three-year EFS and OS were 24%. The median survival after diagnosis was only 29 months. None of the criteria appeared to be significantly associated with a better outcome, but first-line intensification and a short delay after initial diagnosis may be favorable. CONCLUSION: In this study we were not able to confirm the hypothetical benefit of high-dose chemotherapy and PBSC transplantation in mantle cell lymphoma, even though this approach may be promising in a subgroup of patient.

Antineoplastic Agents, Alkylating↗
PubMed1997

Distribution of the cytogenetic abnormality +i(3)(q10) in persistent polyclonal B-cell lymphocytosis: a FICTION study in three cases.

Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity characterized by a moderate but sustained lymphocytosis where some binucleated or bilobulated circulating forms constitute, even if they are not entirely specific, the cytological hallmark of the disease. An additional chromosome long arm i(3)(q10) has recently been reported as a recurrent cytogenetic aberration, contrasting with a usual polyclonal immunoglobulin expression. To determine more precisely the distribution of the chromosomal abnormality within the peripheral lymphocyte population and study the relationship between the +i(3)(q10) and the bilobulated character, we investigated three new cases of PPBL displaying the cytogenetic abnormality on the karyotype, using a technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION). We demonstrated that the +i(3)(q10) was restricted to the B lymphocytes, independently of the kappa or lambda light chain isotype and was present in both bilobulated and non-bilobulated cells. Therefore it is likely that the cytogenetic abnormality occurs at an early stage of lymphocyte differentiation in a precursor cell already committed to the B-cell lineage, before any rearrangement of immunoglobulin genes has taken place.

Adult↗
PubMed1997

Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients.

PURPOSE: A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas. PATIENTS AND METHODS: One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status > or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, > or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P < .0001), and overall survival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI. CONCLUSION: TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.

Antigens, CD↗
PubMed1997

Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients.

PURPOSE: To assess the incidence of lymphoma transformation in the natural history of follicular lymphoma (FL) patients and the factors that are predictive of this event. PATIENTS AND METHODS: Two hundred twenty patients with FL treated in our institution between 1975 and 1990, with a median follow-up duration of 9 years, were included in this retrospective analysis. RESULTS: Transformation was proven by histology in 34 patients or by cytology in 13 patients and was considered as highly probable on clinical arguments in five patients for an overall incidence of 24%. The probability of transformation was 22% at 5 years and 31% at 10 years and tended to plateau after 6 years. Predictive factors for transformation were nonachievement of complete remission (CR) after initial therapy (P < 10(-4), low serum albumin level (< 35 g/L) (P = .001), and beta 2-microglobulin level greater than 3 mg/L (P = .02) at diagnosis. In a multiparametric analysis, only beta 2-microglobulin level retained prognostic significance for freedom-from-transformation (FFT) survival (P = .04). Transformation accounted for 44% of deaths and was associated with a poor outcome, with a median survival time of 7 months. CONCLUSION: Transformation is an early event in the course of the disease and is mainly observed in patients with known adverse prognostic factors or those who do not achieve CR after initial treatment. These findings may be useful to select follicular lymphoma patients for intensive therapeutic approaches.

Adult↗
PubMed1997

Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behavior: analysis of 108 patients.

PURPOSE: Characteristics and outcome of 108 patients with mucosa-associated lymphoid tissue (MALT) lymphoma were analyzed according to initial location of the lymphoma, within or outside of the gastrointestinal (GI) tract. PATIENTS AND METHODS: One hundred eight patients with MALT lymphoma were studied. Fifty-five patients (51%) had GI involvement and 53 patients (49%) had another involved extranodal site: 13 orbit; 11 lung; 10 skin; seven parotid; six thyroid; three Waldeyer's ring; two breast; and one pancreas involvement. At diagnosis, 47 patients (44%) had stage IE, 26 (24%) had stage IIE, and 35 (32%) had disseminated disease. No significant difference in the clinical or biologic characteristics was observed between GI and non-GI patients. RESULTS: Complete response after the first treatment was reached in 76% of the patients, with no difference between the two subgroups. With a median follow-up of 52 months, median survival was not reached and was identical in the two subgroups, but GI MALT patients had a longer time to progression (8.9 years compared with 4.9 years in non-GI patients; P = .01). The different non-GI locations seemed to have a similar outcome. CONCLUSION: MALT lymphoma is an indolent disease that usually presents as localized extranodal tumor without accompanying adverse prognostic factor, and these patients have a good outcome. However, non-GI patients seem to progress more often than GI patients.

Adult↗
PubMed1997

Prognostic significance of TNF alpha and its p55 soluble receptor in malignant lymphomas.

In 93 newly diagnosed lymphoma patients, tumor necrosis factor alpha (TNF alpha) and its p55 soluble receptor (p55-sR), were prospectively determined in plasma by IRMA and ELISA methods respectively. These 93 patients included 31 patients with low grade lymphoma, 55 with intermediate or high grade lymphoma and 7 with Hodgkin's disease. Median TNF alpha plasma values were 20 pg/mL (range 5-380 pg/mL) in patients versus 7 pg/mL (range 4-9 pg/mL) in healthy control subjects. Presence of TNF alpha level equal or greater than 20 pg/mL was significantly associated with elevated LDH level, serum beta 2-microglobulin level > or = 3 mg/L, hemoglobin < or = 12 g/dL, Ann Arbor stage III or IV disease, and with bulky tumor. High level of TNF alpha was also associated, although less strongly, with B symptoms, poor performance status, and serum albumin < or = 35 g/L, yet it was not associated with change in acute phase protein levels. Levels of p55-sR were also markedly elevated in these lymphoma patients (median of 3.5 ng/mL, range 0.8-18.8 ng/mL) versus 1.45 ng/mL in control subjects (range 1.1-2.3 ng/mL). Level of p55-sR equal or greater than 3.5 ng/mL was significantly associated with poor performance status, B symptoms, beta 2-microglobulin levels > or = 3 mg/L, serum albumin < or = 35 g/L, C-reactive protein > 6 mg/L, hemoglobin < or = 12 g/dL, and bulky tumor. In the whole group of 93 patients, both high TNF alpha and p55-sR levels strongly predicted short freedom from progression and overall survival. This study suggests that elevated TNF alpha and p55-sR plasma levels have a high correlation with other adverse prognostic factors in lymphoma patients and predict their poor outcome.

Antigens, CD↗
PubMed1997

[Contribution of dual CD13/CD14 markers in combination with CD34 for the collection of peripheral hematopoietic stem cells].

We evaluated the reliability of a flow cytometry technique for counting mononuclear cells (MNCs) in cytapheresis products. Eighty freshly-prepared samples of peripheral stem cells were studied using a dual immunolabeling technique with antibodies to CD13/CD14, and were also labeled with anti-CD34. Results of this immunophenotype determination were compared to those of the conventional method for counting MNCs under the microscope. Dual CD13/CD14 labeling was found to be a simple and reliable method for counting MNCs in the presence of immature and stimulated cells. When used in combination with CD34 labeling, the dual immunolabeling method helped improve the evaluation of the quality of peripheral stem cell grafts.

Antigens, CD34↗
PubMed1996

Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA).

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

Adult↗
PubMed1996

Elevated circulating levels of TNFalpha and its p55 soluble receptor are associated with an adverse prognosis in lymphoma patients.

In 88 newly diagnosed lymphoma patients, tumour necrosis factor alpha (TNFalpha) and soluble TNF type I receptor (p55-R-TNF) were prospectively determined in plasma by immunoradiometric assay (IRMA) and ELISA methods respectively. These 88 patients included 19 with centrocyto-centroblastic lymphoma, 13 patients with other low-grade lymphoma, and 56 with high-grade lymphoma. Median TNFalpha plasma values were 20 pg/ml (range 5-380 pg/ml) in patients versus 7 pg/ml (range 4-9 pg/ml) in 20 healthy control subjects. Presence of TNFalpha level > or = 20 pg/ml was significantly associated with elevated LDH level (P<0.0001), serum beta2-microglobulin level > or = 3 mg/l (P<0.0001), haemoglobin < or = 12 g/dl (P=0.0001), Ann Arbor stage III or IV disease (P<0.005), and with bulky tumour (P=0.01). High level of TNFalpha was also associated with B symptoms (P<0.005), poor performance status (P<0.05), and serum albumin < or = 35 g/l (P<0.05). Levels of p55-R-TNF were also markedly elevated in these lymphoma patients (median of 3.5 ng/ml, range 0.8-18.8 ng/ml) versus 1.45 ng/ml in control subjects (range 1.1-2.3 ng/ml). Level of p55-R-TNF > or = 3.5 ng/ml was significantly associated with poor performance status (P<0.0001), B symptoms (P<0.0001), beta2-microglobulin levels > or = 3 mg/l (P<0.0001), serum albumin < or = 35 g/l (P=0.0001), C-reactive protein > 6 mg/l (P=0.0003), elevated (>20 pg/ml) IL-6 level (P<0.005), haemoglobin < or = 12 g/dl (P<0.005), and bulky tumour (P<0.001). In the whole group of 88 patients, both high TNFalpha and p55-R-TNF levels strongly predicted short progression-free survival (P<0.005 for both variables) and overall survival (P<0.001 and P<0.001 respectively). In multivariate analyses the elevation of p55-R-TNF retained a higher significance over the other variables and therefore improved the predictive value of the International Prognostic Index. This study suggests that elevated TNF gamma and p55-R-TNF levels have high correlation with other adverse prognostic factors in lymphoma patients and may predict a poor outcome.

Aged↗
PubMed1996

POEMS syndrome, arterial thrombosis and thrombocythaemia.

The case of a 22-year-old man with polyneuropathy, endocrinopathy, skin change and monoclonal gammopathy of IgG-lambda type is described. There was no solitary plasmocytoma, osteosclerotic myeloma or Castleman's disease. However, significant thrombocytosis occurred and the patient developed arterial thrombosis, these were attributed to essential thrombocythaemia in the absence of other aetiological factors.

Adult↗