Biomedical subjects

J Esteve

Publications and source records attributed to J Esteve.

At least 19 recordsLinked to original sources

PubMed2007

Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age <or=40 and male gender were favorable variables for survival, whereas molecular response predicted longer leukemia-free survival. In conclusion, early institution of salvage therapy at molecular failure, before onset of hematological relapse, is beneficial in APL. Moreover, given the poor outcome of HEMrel managed with ATRA and HDAC, use of alternative therapeutic strategies in this setting is warranted.

Adolescent↗

PubMed2006

HLA-identical sibling allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning compared to autologous peripheral blood stem cell transplantation for elderly patients with de novo acute myeloid leukemia.

We conducted a retrospective registry-based analysis to compare the outcome of 361 allogeneic human leukocyte antigen (HLA)-identical peripheral blood stem cell transplants (PBSCT) with reduced intensity conditioning (RIC) to that of 1369 autologous (auto) PBSCT in patients aged 50 years or older with de novo acute myeloid leukemia (AML), performed from 1997 until 2003 and reported to the European Group for Blood and Marrow Transplantation. Median age was 58 and 57 years in the RIC and auto groups, respectively. RIC patients had more advanced disease at the time of transplant. At a median follow-up of 24 months for RIC and 16 months for auto, multivariate analysis showed a lower risk for relapse (RR 0.77, P=0.013) without increased non-relapse mortality (NRM) in RIC patients (RR 1.26, P=0.28). Moreover, leukemia-free survival (RR 1.22, P=0.02) and overall survival (OS) (RR 1.32, P=0.005) were superior in the RIC group. In patients in 1st (CR), fewer relapses were counterbalanced by significantly increased NRM. Therefore, there was no survival advantage in this subgroup. In patients in 2nd or subsequent CR, LFS and OS were superior in the RIC group. RIC transplants show encouraging results in this older patient population with de novo AML.

Aged↗

PubMed2006

Observations of density fluctuations in an elongated Bose gas: ideal gas and quasicondensate regimes.

We report in situ measurements of density fluctuations in a quasi-one-dimensional 87Rb Bose gas at thermal equilibrium in an elongated harmonic trap. We observe an excess of fluctuations compared to the shot-noise level expected for uncorrelated atoms. At low atomic density, the measured excess is in good agreement with the expected "bunching" for an ideal Bose gas. At high density, the measured fluctuations are strongly reduced compared to the ideal gas case. We attribute this reduction to repulsive interatomic interactions. The data are compared with a calculation for an interacting Bose gas in the quasicondensate regime.

Journal Article↗

PubMed2005

Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients.

BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.

Acute Disease↗

PubMed2005

Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT).

Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II-IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10(-4), respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.

Aged↗

PubMed2004

High-dose therapy/autologous stem cell transplantation in patients with chemosensitive multiple myeloma: predictors of complete remission.

High-dose therapy (HDT) followed by autologous stem cell support is widely used as intensification treatment in patients with multiple myeloma (MM) responsive to the initial chemotherapy. However, there is growing evidence that only the subset of patients who achieve complete remission (CR) actually benefit from this approach. The aim of this study was to identify pretransplant predictors of CR in responding myeloma patients intensified with HDT. A total of 59 patients with chemosensitive disease received myeloablative therapy. The intensification regimen consisted of MEL-200 (23), MEL-140/TBI 12 Gy (21) or busulfan-based regimens (15). Serum and urine negative immunofixation were required for CR. After HDT, the CR rate increased from 8 to 37%. For the overall series, the median event-free survival (EFS) and overall survival (OS) from the initiation of therapy were 41 and 68 months, respectively. Patients who achieved CR had an EFS (median 47 vs 36 months; P=0.023) as well as an OS (median not reached vs 60 months; P=0.006) significantly longer than those attaining a lower degree of response. Finally, the pretransplant features significantly associated to CR were a low M-protein size (serum </=10 g/l and urine <0.5 g/24 h) (P=0.0003) and a proportion of bone marrow plasma cells of </=5% (P=0.02).

Adult↗

PubMed2004

Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progression.

BACKGROUND: Different prognostic scores have been proposed to predict the outcome of follicular lymphoma (FL) patients at diagnosis. A new prognostic index specifically addressing FL patients, the Follicular Lymphoma International Prognostic Index (FLIPI), has recently been developed, which might also be useful in patients with progression. PATIENTS AND METHODS: One hundred and three patients (55 male, 48 female; median age 59 years) with FL in first relapse/progression after an initial response to therapy (50 complete responders/ 53 partial responders) were included in the study. RESULTS: Five-year survival from progression (SFP) was 55% (95% confidence interval 44%-66%). The distribution according to the FLIPI at relapse was 39% good prognosis, 24% intermediate prognosis and 37% poor prognosis. Five-year SFP for these groups were 85%, 79% and 28%, respectively (P < 0.0001). Other variables at relapse with prognostic significance for SFP were age, presence of B symptoms, performance status, bulky disease, number of involved nodal sites, lactate dehydrogenase level, hemoglobin level, histological transformation, the Italian Lymphoma Intergroup prognostic index for FL and the International Prognostic Index for aggressive lymphomas. In the multivariate analysis bulky disease (P=0.01), presence of B symptoms (P=0.03) and FLIPI at relapse (P=0.0003) were the most important variables for predicting SFP. CONCLUSIONS: In patients with FL at first relapse/progression, the FLIPI, along with the presence of bulky disease and B symptoms, are features that predict SFP and thus could be useful to select candidates for experimental treatments.

Age Factors↗

PubMed2003

Therapy-related acute promyelocytic leukemia.

PURPOSE: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. PATIENTS AND METHODS: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. RESULTS: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin's lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine-based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. CONCLUSION: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II-targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.

Adult↗

PubMed2003

Smoldering multiple myeloma: natural history and recognition of an evolving type.

Patients with smoldering multiple myeloma (SMM) meet the diagnostic criteria of multiple myeloma (MM) but are asymptomatic. Between January 1978 and July 2001, 53 patients (median age 63 years) were diagnosed with SMM. The median serum M-protein and proportion of bone marrow plasma cells were 36 g/l and 27% respectively. Two subsets of SMM were identified: (i) evolving SMM (n = 22), characterized by a progressive increase in serum M-protein, a previously recognized monoclonal gammopathy of undetermined significance (MGUS) and a significant higher proportion of IgA type and (ii) non-evolving SMM (n = 26) with stable M-protein that abruptly increases when symptomatic MM develops. Thirty-four patients developed symptomatic MM. The median time to progression in the overall series was 3.2 years and the only feature associated with a shorter time to progression was the evolving versus non-evolving type (1.3 vs. 3.9 years respectively, P = 0.007). The pattern of progression consisted of anaemia, lytic bone lesions or both, without renal failure, hypercalcaemia or extramedullary plasmacytomas. Fifty-seven per cent of patients that required chemotherapy showed no or minimal response. The median survival from diagnosis and from progression was 8.2 and 3.5 years respectively.

Adult↗

PubMed2003

Malignant transformation in IgM monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), or primary amyloidosis (AL). Although one fourth of these individuals will develop a malignant disease, there are no well-established predictors of outcome, particularly in the IgM type MGUS. Among 434 patients diagnosed with MGUS from 1970 to 2001 with a minimum follow-up of 1 year, 52 (27 men and 25 women; median age, 67 years) of IgM type were identified. After a median follow-up of 5 years, five patients (9.6%) have developed WM. The risk of transformation was 13.3% (95% confidence interval [CI], 0 to 27) and 27.7% (95% CI, 0.3 to 55.1) at 10 and 20 years, respectively. The variables significantly associated with transformation were the proportion of bone marrow plasma cells (BMPC) and the percentage of bone marrow lymphocytes (BML). No significant differences in the risk of transformation were found between IgM MGUS and the remaining MGUS types. Thus, in IgM MGUS the rate of transformation was similar to the risk observed in other MGUS types, the percentage of BMPC and BML being the features significantly associated with evolution into WM.

Aged↗

PubMed2002

Incidence of thyroid cancer in adults recorded by French cancer registries (1978-1997).

This article analyses time trends and geographical variations of thyroid cancer by histological type. Incidence data were provided by 8 French cancer registries over the period 1978-1997, with 3853 adult cases reported. To assess the effects of age, period, cohort and area on incidence, log-linear Poisson regression models were used. Thyroid cancer increased exponentially from the cohort born in 1925. This increase was essentially due to papillary cancer, which increased by 6.2% per year in men and 8.1% per year in women over the entire period (1978-1997). In women, the recent trends were significantly different between the studied geographical areas. The analysis shows that the increase in thyroid cancer, essentially of the papillary type, is not recent. It may be attributed to a possible screening effect or to an increase in the number of "incidentally" discovered cases linked to the use of modern diagnostic tools.

Adenoma↗

PubMed2002

Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia.

To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21(Waf1)immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21(Waf1) gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL.

Adult↗

PubMed2002

Benefit of operative mortality reduction on colorectal cancer survival.

BACKGROUND: The aim of this study was to determine trends in operative mortality after colorectal cancer surgery over a 20-year period in a well defined population, and consequences on overall survival. METHODS: Some 4745 new cases of colorectal adenocarcinoma were registered between 1976 and 1995 in a French region containing 500 000 people. Among these, 84.3 per cent were operated on, of whom 78.1 per cent were resected. RESULTS: The overall operative mortality rate decreased from 17.7 to 8.1 per cent between 1976-1979 and 1992-1995. Corresponding rates after curative surgery were 12.6 and 6.2 per cent respectively. Period of diagnosis, age and subsite were factors independently associated with operative mortality. Applying the operative mortality rates for the interval 1976-1979 to the 1992-1995 cohort, the expected 5-year survival rate after curative surgery would have been 40.0 per cent, compared with an observed rate of 51.0 per cent. This corresponds to a 27.5 per cent improvement in 5-year overall survival. Applying this result to the French population as a whole, it was estimated that almost 3000 deaths are avoided each year in France as a result of the reduction in operative mortality. CONCLUSION: Operative mortality decreased dramatically over the 20 years of the study. It was associated with a significant improvement in survival after surgery for cure.

Adenocarcinoma↗

PubMed2002

Survival after progression in patients with follicular lymphoma: analysis of prognostic factors.

BACKGROUND: The purpose of this study was to identify prognostic parameters for patients with follicular lymphoma (FL) in first progression/relapse. These would be useful for selection of high-risk patients for inclusion in trials aimed at determining the effect of new treatment approaches in such patients. PATIENTS AND METHODS: Ninety patients (48 male, 42 female, median age 56 years) diagnosed with FL, in a single institution during a 20 year period and relapsing/progressing after an initial response to therapy, were recruited. The main end-point of the study was survival from progression (SFP). Univariate and multivariate analyses were performed, including among the predictive variables the response duration (RD) after the initial treatment and the main features of the patients at the first progression or relapse. RESULTS: Five-year SFP was 47% (95% confidence interval 35% to 58%). Patients with RD following initial therapy >2 years had a longer SFP (5-year SFP 63 versus 33%, P = 0.012). Other variables with prognostic interest for SFP were stage at diagnosis and the following variables at relapse: age, bulky disease, performance status, serum lactate dehydrogenase level, serum beta2-microglobulin level, bone marrow involvement, stage and International Prognostic Index rating. In the multivariate analysis, poor performance status at progression and a RD <2 years were the most important unfavorable variables to predict SFP. CONCLUSION: In patients with FL, RD along with performance status at progression are features that predict SFP. These variables could thus be useful to select candidates for experimental treatments.

Age Factors↗

PubMed2002

Trends in gastric cancer incidence in a well-defined French population by time period and birth cohort.

Epidemiological studies have shown a marked decline in gastric cancer incidence and opposite patterns between proximal and distal sites among different populations. Little is known about trends by histological type. The aim of this study was to analyse the change in gastric cancer incidence patterns by investigating the role of temporal components as determinants of such trends in the population of the Côte d'Or area (France) registered between 1976 and 1995. Gastric cancer incidence decreased over time. There was a decrease in incidence rates for distal cancers (-3.5% P < 0.001 per year in men and -4.6% P < 0.01 in women). In contrast, there was a non-significant increase of proximal cancer incidence in men and in women. Rates of adenocarcinomas decreased, whereas the incidence rates of undifferentiated carcinomas and of other histological types remained quite stable. There was a decrease in cumulative risk throughout the studied cohorts, whereas risk for proximal cancer remained stable and decreased slightly for distal localization. For adenocarcinomas, earlier birth cohorts showed a slight decrease in rates, whereas there was an increase for recent cohorts. Subsite and histological-specific analysis, in revealing different time trends in incidence, suggest, at least partly, different aetiologies for gastric cancer, and future aetiological studies must distinguish proximal and distal cancers.

Adult↗

PubMed2002

Assessing time-by-covariate interactions in relative survival models using restrictive cubic spline functions.

BACKGROUND: The Cox model is widely used in the evaluation of prognostic factors in clinical research. However, in population-based studies, which assess long-term survival of unselected populations, relative-survival models are often considered more appropriate. In both approaches, the validity of proportional hazards hypothesis should be evaluated. METHODS: We propose a new method in which restricted cubic spline functions are employed to model time-by-covariate interactions in relative survival analyses. The method allows investigation of the shape of possible dependence of the covariate effect on time without having to specify a particular functional form. Restricted cubic spline functions allow graphing of such time-by-covariate interactions, to test formally the proportional hazards assumption, and also to test the linearity of the time-by-covariate interaction. RESULTS: Application of our new method to assess mortality in colon cancer provides strong evidence against the proportional hazards hypothesis, which is rejected for all prognostic factors. The results corroborate previous analyses of similar data-sets, suggesting the importance of both modelling of non-proportional hazards and relative survival approach. We also demonstrate the advantages of using restricted cubic spline functions for modelling non-proportional hazards in relative-survival analysis. The results provide new insights in the estimated impact of older age and of period of diagnosis. DISCUSSION: Using restricted cubic splines in a relative survival model allows the representation of both simple and complex patterns of changes in relative risks over time, with a single parsimonious model without a priori assumptions about the functional form of these changes.

Aged↗

PubMed2001

Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species.

Mechanisms involving the in vitro effect of rituximab in cells from 55 patients with B-cell lymphoproliferative disorders were investigated. No cytotoxic effect was observed when cells were incubated with rituximab alone, but in the presence of human AB serum rituximab induced complement-dependent cell death (R-CDC). A cytotoxic effect was observed in cells from 9 of 33 patients with B-cell chronic lymphocytic leukemia, 16 of 16 patients with mantle-cell lymphoma, 4 of 4 patients with follicular lymphoma, and 2 of 2 patients with hairy-cell leukemia. R-CDC was observed in cells from patients expressing more than 50 x 10(3) CD20 molecules per cell, and directly correlated with the number of CD20 molecules per cell. Preincubation with anti-CD59 increased the cytotoxic effect of rituximab and sensitized cells from nonsensitive cases. Neither cleavage of poly-ADP ribose polymerase (PARP) nor activation of caspase-3 was observed in R-CDC. In addition, no cells with a hypodiploid DNA content were detected and R-CDC was not prevented by a broad-spectrum caspase inhibitor, suggesting a caspase-independent mechanism. Incubation with rituximab in the presence of AB serum induced a rapid and intense production of reactive oxygen species (ROS). R-CDC was blocked by the incubation of cells with N-acetyl-L-cysteine (NAC) or Tiron, 2 ROS scavengers, indicating that the cytotoxic effect was due to the generation of superoxide (O) radicals. In conclusion, the results of the present study suggest that CD20, CD59, and complement have a role in the in vitro cytotoxic effect of rituximab, which is mediated by a caspase-independent process that involves ROS generation.

Adult↗

PubMed2001

Estimation of screening test (Hemoccult) sensitivity in colorectal cancer mass screening.

3 controlled cohorts of mass-screening for colorectal cancer using a biennial faecal occult blood (HemoccultII test on well-defined European populations have demonstrated a 14% to 18% reduction in specific mortality. We aimed to estimate the sensitivity (S) of this HemoccultII test and and also mean sojourn time (MST) from French colorectal mass-screening programme data. 6 biennial screening rounds were performed from 1988 to 1998 in 45 603 individuals aged 45-74 years in Saône-et-Loire (Burgundy, France). The prevalent/incidence ratio was calculated in order to obtain a direct estimate of the product S.MST. The analysis of the proportional incidence and its modelling was used to derive an indirect estimate of S and MST. The product S.MST was higher for males than females and higher for left colon than either the right colon or rectum. The analysis of the proportional incidence confirmed the result for subsites but no other significant differences were found. The sensitivity was estimated at 0.57 and the MST at 2.56 years. This study confirms that the sensitivity of the Hemoccult test is relatively low and that the relatively short sojourn time is in favour of annual screening.

Aged↗