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Biomedical subjects

X Troussard

Publications and source records attributed to X Troussard.

At least 19 recordsLinked to original sources
PubMed2006

Survival of cancer patients in France: a population-based study from The Association of the French Cancer Registries (FRANCIM).

We present the main results of the first population-based cancers survival study gathering all French registry data. Survival data on 205,562 cancer cases diagnosed between 01/01/1989 and 31/12/1997 were analysed. Relative survival was estimated using an excess rate model. The evolution of the excess mortality rate over the follow-up period was graphed. The analysis emphasised the effect of age at diagnosis and its variation with time after diagnosis. For breast and prostate cancers, the age-standardised five-year relative survivals were 84% and 77%, respectively. The corresponding results in men and women were 56% versus 58% for colorectal cancer and 12% versus 16% for lung cancer. For some cancer sites, the excess mortality rate decreased to low values by five years after diagnosis. For most cancer sites, age at diagnosis was a negative prognostic factor but this effect was often limited to the first year after diagnosis.

Adolescent↗
PubMed2006

Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study.

Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study. Patients in the MLL group had higher WBC counts and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a donor were assigned to alloSCT (n=22), the remaining patients with were randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The results of this study show that chemotherapy intensification did not overcome the poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New therapeutic approaches are needed for patients without donor.

Adolescent↗
PubMed2006

Non-Hodgkin's lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis.

Out of 344 patients with newly diagnosed non-Hodgkin's lymphoma (NHL), this study identified 16 patients presenting Burkitt-like cells (BLCs) after cytological and/or histological review. Conventional cytogenetic analysis showed at diagnosis complex chromosomal abnormalities in 13 cases and a normal karyotype in three cases. However, neither t(8;14)(q24;q32) nor the variants t(2;8)(p12;q24) or t(8;22)(q24;q11) was detected. FISH studies showed c-MYC amplification in all cases with four to more than seven copies in 10 - 77% metaphase or inter-phase cells. This study did not observe any gene fusion signal for c-MYC/IgH excluding a t(8;14) translocation and partial tri or polysomy of chromosome 8. It also excluded in that cases a break apart for the c-MYC locus. This study also never detected IgL/c-MYC, IgK/c-MYC or X-c-MYC. The BLCs were present whatever the lymphoma sub-type: follicular lymphoma (FL) was diagnosed in six out of 16 patients, mantle cell lymphoma (MCL) in four out of 16 patients, marginal zone lymphoma (MZL) in two out of 16 patients and diffuse large B-cell lymphomas (DLBCL) in three out of 16 patients. One additional patient presented a T-cell lymphoma. The clinical course was aggressive with a poor prognosis, as death occurred in nine patients, within 6 months after diagnosis for eight of them. These data could suggest a sub-group of NHL patients (15 B-NHL, 1 T-NHL) have been identified with a poor prognosis characterized by the association of Burkitt-like cells and c-MYC amplification without t(8;14)(q24;q32) or its variants. The possibility that this profile may represent a distinct morphologic NHL sub-set remains to be determined on a large cohort of patients.

Adult↗
PubMed2004

Prognostic impact of p27KIP1 expression in cyclin D1 positive lymphoproliferative disorders.

Nodal mantle cell lymphoma (MCL) is a well-defined entity, but non-nodal leukemic cyclin D1 positive lymphoproliferative disorders have been reported and their relationship with MCL remains controversial and their prognosis heterogeneous. We prospectively studied the expression of cyclin D1 in CD5 positive leukemic B lymphoproliferative disorders at diagnosis and identified 65 cases overexpressing cyclin D1. We did not distinguish any clinical or biological criteria allowing one to identify a non-MCL group. Multivariate analysis identified age, anemia and p27kip1 expression as independent prognostic factors of survival. By univariate analysis, p27kip1 high expression proved to be the strongest predictor of prolonged survival. The median survival of p27 low expressors was 30 months, while it was not reached for p27 high expressors. A high level of p27 expression was often found associated with the absence of nodal involvement and the presence of somatic mutations, but neither of them was restricted to the p27 high expression group. In conclusion, we hypothesize that MCL and these cyclin D1 positive leukemic lymphoproliferative disorders represent a continuous spectrum of diseases. Determination of p27 expression level appears as a routine applicable test allowing identification of a subset of patients who could be considered for different therapeutic approaches.

Adult↗
PubMed2004

Chromosomal instability and ATR amplification gene in patients with persistent and polyclonal B-cell lymphocytosis (PPBL).

Forty-three patients with persistent and polyclonal B-cell lymphocytosis (PPBL) were studied. The PPBL diagnosis was based on the presence of a polyclonal lymphocytosis and the detection of binucleated lymphoid cells on peripheral blood examination. In order to define the cytogenetic profile in these patients, conventional cytogenetic analysis and fluorescence in situ hybridization were performed at diagnosis in all patients and also at follow-up in 10 patients. When excluding + i(3q) and PCC, chromosomal instability is a common occurrence in PPBL and is characterized by other independent clonal abnormalities, del(6q), + der(8) or + 8, polyploid karyotype, structural changes, aneuploidy and/or non clonal chromosomal aberrations with either loss or more frequently gain of chromosomes. These data show the presence of a chromosomal instability in 67.5% of PPBL patients. Finally, ATR amplification was detected by hybridization with BAC probe 26217 in + i(3q) positive metaphase cells. No ATR deletion was observed in the + i(3q) negative B-cells. As the natural history of PPBL remains unclear, it is necessary to diagnose PPBL patients and useful to recommend a careful and continued long follow-up in all PPBL patients.

Adult↗
PubMed2003

Cancer incidence and mortality in France over the period 1978-2000.

BACKGROUND: Monitoring cancer incidence and mortality time trends is essential for cancer research and health-care planning. French cancer registries do not cover the entire population and do not provide a representative sample of the national population. Our study aimed at estimating national cancer incidence and mortality trends over the longest period available. METHODS: Incidence and mortality data were collected over the period 1978-1997. Twenty-seven cancer sites were selected and age, sex and site specific incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The person-years of observation were calculated cohort-wise from census data provided by the national institute of statistics RESULTS: Cancer incidence increased by 63% throughout the study period, from 170,000 new cases in 1980 to 278,000 in 2000. This evolution was due to demographic changes but also to an increase in the risk of cancer which was estimated to more than 35% during the same period. In men, this change is largely explain by the increase of prostate cancer incidence. Among women, the increase was dominated by the continuing increase in breast cancer incidence. Large increases were also seen for non-Hodgkin lymphoma, melanoma, and thyroid cancer in both genders and for lung cancer in women. Cancer mortality increased by 20% from 125,000 deaths in 1980 to 150,000 in 2000. This increase is less than that predicted from changes in demographic factors and corresponds in fact to a decrease in the risk of death estimated to about 8%, slightly greater for women than for men. This decrease is associated with a decreasing incidence for stomach cancers for both sexes, alcohol-related cancer for men and cervical cancer for women. Colo-rectal cancer decreasing mortality contributes to this improvement despite an incidence increase. CONCLUSION: Between 1980 and 2000, the study showed a large change in the cancer burden both quantitatively and qualitatively. Decrease in exposure, earlier diagnosis and therapeutic improvement explained part of this change, but overall the distribution of cancer cases shifted toward a distribution including less aggressive cancers. A striking divergence between incidence and mortality trends is observed for a great number of cancers. Prostate cancer shares with breast cancer the same pattern of a severe increasing incidence and a stable mortality. This points to important changes in medical practice and needs further analysis. The trend of lung cancer mortality among women should be emphasised since the situation will inevitably worsen in the coming years. It is already the third cause of cancer death among women.

Age Distribution↗
PubMed2002

Dicentric chromosome 3 associated with binucleated lymphocytes in atypical B-cell chronic lymphoproliferative disorder.

Binucleated lymphocytes on blood smear are known in PPBL characterized by stable and polyclonal lymphocytosis, polyclonal increase of serum IgM, HLA DR7 and strong correlation with additional i(3q) and premature chromosome condensation. In this disorder some reports of clonal Ig rearrangement suggest a follow up of these patients with immunological and genetic studies. Binucleated lymphocytes are rarely described in other clonal B-CLPD as B-CLL or marginal zone B-cell lymphoma (MZL). Chromosome 3 abnormality is never described in B-CLL but trisomy 3 represents the most consistent abnormality characterizing the MZL. We report in a man without previous medical history an unusual B-CLPD with monoclonal lymphocytosis CD5-, characteristic cytology (particularly binucleated lymphocytes) and chromosomic abnormality as dicentric chromosome 3 never previously described in B-CLPD. In this case lymphocytosis is persistent and stable over 24 months, cytologic immunologic and chromosomic abnormalities are unchanged. We discuss the nosologic place of this atypical B-CLPD closely related to PPBL and MZL with at the moment, after 24 months, a quiet evolution that imply nevertheless a careful follow up with regular cytologic, immunological and genetic studies to clarify the issue.

B-Lymphocytes↗
PubMed2001

Upstream mediators of the Fas apoptotic transduction pathway are defective in B-chronic lymphocytic leukemia.

Data concerning the presence and the functionality of Fas receptor in malignant B-cells are controversial. We have analyzed Fas molecules on B-cells from patients with B-chronic lymphocytic leukemia (B-CLL) cells. We observed a large variability, both of percentage of Fas-positive cells and of intensity of Fas level. Fas triggering was inefficient in inducing apoptosis whatever the number of Fas-positive B-cells, the amount of Fas receptors. B-cells were also resistant to etoposide treatment, but able to undergo apoptosis after dexamethasone treatment. We suggest that the Fas apoptotic pathway is altered in B-CLL patients at the initial step(s) of apoptotic machinery.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Ectopic expression of cyclin D1 impairs the proliferation and enhances the apoptosis of a murine lymphoid cell line.

Cyclin D1, a key regulator of the cell cycle, acts as an oncogene when over-expressed in several types of cancer. In some B-chronic lymphoproliferative disorders, the over-expression of cyclin D1 protein is thought to confer a proliferative phenotype. We have generated BaF3 pro-B cell derivatives in which cyclin D1 can be induced rapidly and reversibly in a dose-dependent manner by the hormone muristerone A. When non-expressing clones displayed the same proliferative capacity as the parental cell line, in the sub-clones, a moderate induction of cyclin D1 lengthened the proliferation rate. The over-expression of cyclin D1 had the same effects on cell proliferation but also led ultimately to cell death by apoptosis. The induction of cyclin D1 in growth factor-deprived cells as well as in anticancer drug-treated cells also reinforced the magnitude of apoptosis. Thus, the expression of cyclin D1 in lymphoid cells does not confer a proliferative advantage but rather alters the response of cells towards apoptotic stimuli in a p53-independent manner.

Animals↗
PubMed2001

No BCL-2 protein over expression but BCL-2/IgH rearrangements in B cells of patients with persistent polyclonal B-cell lymphocytosis.

INTRODUCTION: Persistent polyclonal B-cell lymphocytosis is a rare hematological disorder, characterized by a chronic, stable and absolute polyclonal lymphocytosis, the presence of binucleated lymphocytes, a polyclonal increase in serum IgM immunoglobulin and clonal cytogenetic abnormalities involving chromosome 3. For explaining the expansion of B-lymphocytes pool in PPBL, an association with cigarette smoking and/or chronic Epstein-Barr virus infection have been suggested but both hypotheses have been ruled out. MATERIALS AND METHODS: We studied the presence of BCL-2/IgH rearrangements in a series of eight PPBL patients (seven females and one male) by a nested polymerase chain reaction (PCR), targeting the Major Breakpoint Region in BCL-2 locus and we explored the BCL-2 protein expression by Western blot. RESULTS: We demonstrated: (a) the constant presence of BCL-2/IgH rearrangements in eight out of eight DNA samples, (b) multiple rearrangements in three out of eight cases and, (c) normal BCL-2 protein expression, as compared to BCL-2 level in B-lymphocytes from healthy population. CONCLUSION: Despite the presence of BCL-2/IgH rearrangements, the accumulation of B lymphocytes in PPBL is not related to an overexpression of BCL-2 protein.

Adult↗
PubMed2001

The incidence of childhood leukaemia around the La Hague nuclear waste reprocessing plant (France): a survey for the years 1978-1998.

BACKGROUND: A previous study has suggested an increased incidence rate of leukaemia from 1978 to 1992 in people aged 0 to 24 years and living in the vicinity of the La Hague nuclear waste reprocessing plant without considering age and cytological type. SETTING: The Nord Cotentin region (France) and the island of Alderney (United Kingdom). STUDY OBJECTIVE: To describe the occurrence of leukaemia for each age group and cytological type from 1978 to 1998 in the same area, using accurate reference incidence rates and adequate estimation of the at risk population. DESIGN: A geographical study of incidence using three zones defined according to their distance from the site (0 to 10 km: Beaumont-Hague electoral ward, 10 to 20 km and 20 to 35 km) has been conducted. The risk of leukaemia was estimated from the standardised incidence ratio (SIR) of the number of cases observed to the number expected. Exact 95% confidence intervals (CI) have been computed. PARTICIPANTS: All people under the age of 25 years living in the study region between 1978 and 1998. MAIN RESULTS: The observed number of cases of leukaemia in the study region as a whole was consistent with the expected value (SIR=1.03; 95%CI: 0.73, 1.41). No cases were observed on Alderney. The SIR in the Beaumont-Hague electoral ward was 2.17 (95%CI: 0.71, 5.07). The highest SIR was observed in the 5 to 9 years age group (SIR=6.38; 95%CI: 1.32, 18.65). This consists in acute lymphoblastic leukaemia cases. CONCLUSION: This study indicates an increased incidence of leukaemia in the area situated at less than 10 km from the plant. Monitoring and further investigations should be targeted at acute lymphoblastic leukaemia occurring during the childhood incidence peak (before 10 years) in children living near the La Hague site and may be other nuclear reprocessing plants.

Adolescent↗
PubMed2001

Chronic lymphocytic leukemia associated with myelodysplastic syndrome and/or chronic myeloid leukemia: evidence for independent clonal chromosomal evolution.

We describe the cytogenetic findings of three cases with simultaneous or sequential development of a B-chronic lymphocytic leukemia (B-CLL) and either a myelodysplastic syndrome (MDS) in 2 cases or a chronic myeloid leukemia (CML) in one case. The coexistence of these two hematologic malignancies leads to questions about their cell of origin. Through analysis of the cytogenetic abnormalities, we studied the derivation of both malignancies. The cytogenetic analyses of these three patients were simultaneously studied from both peripheral blood and bone marrow. Furthermore unstimulated short-time (USSTC) and long-time (72-96 hours) stimulated cultures (LTSC) were systematically performed. In all cases, we have demonstrated the independent bi-clonal evolution. This is the first report ever described for patients with CLPD and MDS and/or MPD shown to arise from distinct chromosomal abnormalities.

Aged↗