235 results on '"Jean-Pierre Marie"'
Search Results
2. Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype
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Frédéric Baron, Marian Stevens-Kroef, Michal Kicinski, Giovanna Meloni, Petra Muus, Jean-Pierre Marie, Constantijn J.M. Halkes, Xavier Thomas, Radovan Vrhovac, Francesco Albano, François Lefrère, Simona Sica, Marco Mancini, Adriano Venditti, Anne Hagemeijer, Joop H. Jansen, Sergio Amadori, Theo de Witte, Roelof Willemze, and Stefan Suciu
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Monosomal karyotype confers a poor prognosis in patients with acute myeloid leukemia. Here, we determined the impact of the type of remission-induction chemotherapy and the impact of having a donor in younger acute myeloid leukemia patients with a monosomal karyotype included in two phase III trials. In the first trial patients were randomized to receive either daunorubicin, mitoxantrone, or idarubicin in addition to standard-dose cytarabine and etoposide for induction chemotherapy. In the second trial patients were randomized to standard-dose cytarabine or high-dose cytarabine induction, both with daunorubicin and etoposide. In both trials, patients who achieved a complete remission with or without complete hematologic recovery underwent allogeneic hematopoietic stem cell transplantation if they had a donor; otherwise, they underwent autologous transplantation. In comparison to patients with intermediate-risk cytogenetics without a monosomal karyotype (n=1,584) and with adverse cytogenetics without a monosomal karyotype (n=218), patients with a monosomal karyotype (n=188) were more likely not to achieve a complete remission with or without count recovery [odds ratio=2.85, 95% confidence interval (95%, CI): 2.10-3.88] and had shorter overall survival [hazard ratio, (HR)=2.44, 95% CI: 2.08-2.88]. There was no impact of the type of anthracycline or of the dose of cytarabine on outcomes in patients with a monosomal karyotype. Among monosomal karyo type patients who achieved a complete remission with or without count recovery, HLA-identical related donor availability was associated with longer survival from complete remission with or without count recovery (HR=0.59, 95% CI: 0.37-0.95). ClinicalTrials.gov identifiers: AML-10: NCT00002549; AML-12: NCT00004128.
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- 2019
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3. Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials
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Safaa M. Ramadan, Stefan Suciu, Marian J. P. L. Stevens-Kroef, Roelof Willemze, Sergio Amadori, Theo de Witte, Bob Löwenberg, Petra Muus, Boris Labar, Liv Meert, Gaetan de Schaetzen, Giovanna Meloni, Giuseppe Leone, Marco Vignetti, Jean-Pierre Marie, Michael Lübbert, and Frédéric Baron
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AML ,secondary ,trials ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p < 0.001): 7.7% (95% CI: 1.3–21.7%) for patients treated before 1990 (period 1: n = 26), 23.3% (95% CI: 17.1–30.0%) for those treated between 1990 and 2000 (period 2: n = 188) and 36.5% (95% CI: 28.7–44.3%) for those treated in 2000 or later (period 3: n = 153). In multivariate analysis, male gender (HR = 1.39; p = 0.01), WBC ≥ 25 × 109/L (HR = 2.00; p < 0.0001), age 46-60 years (HR = 1.65; p < 0.001) and poor-risk cytogenetics (HR = 2.17; p < 0.0001) were independently associated with shorter OS, while being treated during period 2 (HR = 0.50, p = 0.003) or period 3 (HR = 0.43; p = 0.0008). Having received high-dose cytarabine (HD-AraC) (n = 48) in the induction chemotherapy (HR = 0.54, p = 0.012) was associated with a longer OS. In contrast, among patients >60 years of age (n = 502), the OS was dismal, and there was no improvement over time.
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- 2020
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4. Low-dose clofarabine in combination with a standard remission induction in patients aged 18–60 years with previously untreated intermediate and bad-risk acute myeloid leukemia or high-risk myelodysplastic syndrome: combined phase I/II results of the EORTC/GIMEMA AML-14A trial
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Dominik Selleslag, Stefan Suciu, Giovanna Meloni, Petra Muus, Constantijn J.M. Halkes, Adriano Venditti, Safaa M. Ramadan, Hans Pruijt, Liv Meert, Marco Vignetti, Jean-Pierre Marie, Sébastian Wittnebel, Theo de Witte, Sergio Amadori, Roelof Willemze, and Frédéric Baron
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2017
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5. ATP Binding Cassette transporters associated with chemoresistance: transcriptional profiling in extreme cohorts and their prognostic impact in a cohort of 281 acute myeloid leukemia patients
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Christophe Marzac, Edith Garrido, Ruoping Tang, Fanny Fava, Pierre Hirsch, Cinzia De Benedictis, Elise Corre, Simona Lapusan, Jean-Yves Lallemand, Jean-Pierre Marie, Eric Jacquet, and Ollivier Legrand
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background A major issue in the treatment of acute myeloid leukemia is resistance to chemotherapeutic drugs. An increasing number of ATP-Binding-Cassette transporters have been demonstrated to cause resistance to cancer drugs. The aim of this study was to highlight the putative role of other ATP-Binding-Cassette transporters in primary chemoresistant acute myeloid leukemia.Design and Methods In the first part of this study, using taqman custom arrays, we analyzed the relative expression levels of 49 ATP-Binding-Cassette genes in 51 patients divided into two extreme cohorts, one very sensitive and one very resistant to chemotherapy. In the second part of this study, we evaluated the prognostic impact, in a cohort of 281 patients, of ATP-Binding-Cassette genes selected in the first part of the study.Results In the first part of the study, six genes (ATP-Binding-CassetteA2, ATP-Binding-CassetteB1, ATP-Binding-CassetteB6, ATP-Binding-CassettC13, ATP-Binding-CassetteG1, and ATP-Binding-CassetteG2) were significantly over-expressed in the resistant group compared with the sensitive group. In the second cohort, overexpression of 5 of these 6 ATP-Binding-Cassette genes was correlated with outcome in univariate analysis, and only the well-known ATP-Binding-CassetteB1 and G2, and the new ATP-Binding-CassetteG1 in multivariate analysis. Prognosis decreased remarkably with the number of these over-expressed ABC genes. Complete remission was achieved in 71%, 59%, 54%, and 0%, (P=0.0011) and resistance disease in 21%, 37%, 43%, and 100% (P
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- 2011
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6. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial
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Theo de Witte, Anne Hagemeijer, Stefan Suciu, Amin Belhabri, Michel Delforge, Guido Kobbe, Dominik Selleslag, Harry C. Schouten, Augustin Ferrant, Harald Biersack, Sergio Amadori, Petra Muus, Joop H. Jansen, Eva Hellström-Lindberg, Tibor Kovacsovics, Pierre Wijermans, Gert Ossenkoppele, Alois Gratwohl, Jean-Pierre Marie, and Roel Willemze
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old.Design and Methods We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine.Results The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49–1.35) for survival and of 0.67 (95% CI, 0.42–1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22–1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22–1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40–3.42) and that for disease-free survival was 1.02 (99% CI, 0.40–2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65–2.27) for survival and 1.02 (95% CI, 0.56–1.85) for disease-free survival.Conclusions Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy. (Eudract number: NCT00002926; http://www.cancer.gov/clinicaltrials/EORTC-06961)
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- 2010
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7. Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group
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Boris Labar, Stefan Suciu, Roel Willemze, Petra Muus, Jean-Pierre Marie, Georges Fillet, Zwi Berneman, Branimir Jaksic, Walter Feremans, Dominique Bron, Harm Sinnige, Martin Mistrik, Gerard Vreugdenhil, Robrecht De Bock, Damir Nemet, Caroline Gilotay, Sergio Amadori, and Theo de Witte
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone.Design and Methods Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1–8 and 15–22, either dexamethasone 8 mg/m2 or prednisolone 60 mg/m2. Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis.Results Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75–1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76–1.40). The 6-year cumulative incidences of relapse were 49.8% and 53.5% (Gray’s test: P=0.30) while the 6-year cumulative incidences of death were 18% and 9% (Gray’s test: P=0.07).Conclusions In the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, treatment with dexamethasone did not show any advantage over treatment with prednisolone.
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- 2010
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8. Spectrum of prevalent cardiovascular diseases in urban Port-au-Prince, Haiti: a population-based cross-sectional study
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Yan, Lily D., Sufra, Rodney, St Sauveur, Reichling, Jean-Pierre, Marie Christine, Pierre, Jean Lookens, Apollon, Alexandra, Malebranche, Rodolphe, Théard, Michel, Pierre, Gerard, Dévieux, Jessy, Lau, Jennifer, Mourra, Nour, Metz, Miranda, Smith, Caleigh, Sabwa, Shalom, Clermont, Adrienne, Roberts, Nicholas L.S., Rasul, Rehana, Nash, Denis, Pirmohamed, Altaf M., Devereux, Richard B., Lee, Myung Hee, Kwan, Gene F., Safford, Monika, Adrien, Lauré, Alfred, Jean Patrick, Deschamps, Marie, Severe, Patrice, Fitzgerald, Daniel W., Pape, Jean W., Rouzier, Vanessa, McNairy, Margaret L., and Safford, Monika M.
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- 2024
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9. Oncologic trogocytosis of an original stromal cells induces chemoresistance of ovarian tumours.
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Arash Rafii, Pejman Mirshahi, Mary Poupot, Anne-Marie Faussat, Anne Simon, Elodie Ducros, Eliane Mery, Bettina Couderc, Raphael Lis, Jerome Capdet, Julie Bergalet, Denis Querleu, Francoise Dagonnet, Jean-Jacques Fournié, Jean-Pierre Marie, Eric Pujade-Lauraine, Gilles Favre, Jeanine Soria, and Massoud Mirshahi
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Medicine ,Science - Abstract
BackgroundThe microenvironment plays a major role in the onset and progression of metastasis. Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneal cavity where interactions within the microenvironment might lead to chemoresistance. Mesothelial cells are important actors of the peritoneal homeostasis; we determined their role in the acquisition of chemoresistance of ovarian tumours.Methodology/principal findingsWe isolated an original type of stromal cells, referred to as "Hospicells" from ascitis of patients with ovarian carcinosis using limiting dilution. We studied their ability to confer chemoresistance through heterocellular interactions. These stromal cells displayed a new phenotype with positive immunostaining for CD9, CD10, CD29, CD146, CD166 and Multi drug resistance protein. They preferentially interacted with epithelial ovarian cancer cells. This interaction induced chemoresistance to platin and taxans with the implication of multi-drug resistance proteins. This contact enabled EOC cells to capture patches of the Hospicells membrane through oncologic trogocytosis, therefore acquiring their functional P-gp proteins and thus developing chemoresistance. Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.Conclusions/significanceThis is the first report of trogocytosis occurring between a cancer cell and an original type of stromal cell. This interaction induced autonomous acquisition of chemoresistance. The presence of stromal cells within patient's tumour might be predictive of chemoresistance. The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy.
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- 2008
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10. Abstract 17368: Burden of Cardiovascular Diseases in Haiti: Implications for Low-Income Countries
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Yan, Lily D, Sufra, Rodney, St Sauveur, Reichling, Jean-Pierre, Marie Christine, Macius, Youry, Apollon, Alexandra, Malebranche, Rodolphe, Theard, Michel, Pierre, Gerard, Devieux, Jessy, Lau, Jennifer, Mourra, Nour, Roberts, Nicholas, Rasul, Rehana, Nash, Denis, Lee, Myung Hee, Kwan, Gene F, Safford, Monika M, Adrien, Laure, Alfred, Jean Patrick, Deschamps, Marie, Severe, Patrice, FITZGERALD, Daniel W, Pape, Jean, Rouzier, Vanessa, and Mcnairy, Margaret
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- 2023
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11. A realist evaluation of the continuum of HIV services for men who have sex with men
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Dunbar, Willy, Alcide Jean-Pierre, Marie Colette, Pétion, Jacky S., Labat, Aline, Maulet, Nathalie, and Coppieters, Yves
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- 2021
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12. Studying and Learning a New Language
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White, Marie C., Vélez, Miriam R., Jean-Pierre, Marie Angelica, and DiBenedetto, Maria K., editor
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- 2018
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13. A New Model of Cell Dynamics in Acute Myeloid Leukemia Involving Distributed Delays.
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Jose Louis Avila Alonso, Catherine Bonnet, Jean Clairambault, Hitay özbay, Silviu-Iulian Niculescu, Faten Merhi, Ruoping Tang, and Jean-Pierre Marie
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- 2012
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14. Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype
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Marian Stevens-Kroef, Giovanna Meloni, Simona Sica, Xavier Thomas, Jean-Pierre Marie, Anne Hagemeijer, Constantijn J.M. Halkes, Adriano Venditti, Francesco Albano, Marco Mancini, Joop H. Jansen, Roelof Willemze, Radovan Vrhovac, Stefan Suciu, François Lefrère, Theo de Witte, Michal Kicinski, Petra Muus, Frédéric Baron, and Sergio Amadori
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Oncology ,Male ,BLOOD ,medicine.medical_treatment ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Abnormal Karyotype ,Hematopoietic stem cell transplantation ,Monosomy ,Antineoplastic Combined Chemotherapy Protocols ,Odds Ratio ,IMPROVES ,Medicine ,induction regimen ,allogeneic hematopoietic cell transplantation ,acute myeloid leukemia ,monosomal karyotype ,Etoposide ,Cytogenetics and Molecular Genetics ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Induction Chemotherapy ,Hematology ,Middle Aged ,Prognosis ,Combined Modality Therapy ,HIGH-DOSE CYTARABINE ,Leukemia, Myeloid, Acute ,Treatment Outcome ,WORKING PARTY ,Female ,Life Sciences & Biomedicine ,medicine.drug ,Adult ,Acute Myeloid Leukemia ,medicine.medical_specialty ,Monosomal karyotype ,Transplantation ,Adolescent ,PROGNOSTIC IMPACT ,Article ,Young Adult ,All institutes and research themes of the Radboud University Medical Center ,Internal medicine ,Autologous transplantation ,Idarubicin ,Humans ,Transplantation, Homologous ,EUROPEAN GROUP ,Science & Technology ,business.industry ,INTENSITY ,Induction chemotherapy ,Survival Analysis ,Cytarabine ,business ,Settore MED/15 - Malattie del Sangue - Abstract
Monosomal karyotype confers a poor prognosis in patients with acute myeloid leukemia. Here, we determined the impact of the type of remission-induction chemotherapy and the impact of having a donor in younger acute myeloid leukemia patients with a monosomal karyotype included in two phase III trials. In the first trial patients were randomized to receive either daunorubicin, mitoxantrone, or idarubicin in addition to standard-dose cytarabine and etoposide for induction chemotherapy. In the second trial patients were randomized to standard-dose cytarabine or high-dose cytarabine induction, both with daunorubicin and etoposide. In both trials, patients who achieved a complete remission with or without complete hematologic recovery underwent allogeneic hematopoietic stem cell transplantation if they had a donor; otherwise, they underwent autologous transplantation. In comparison to patients with intermediate-risk cytogenetics without a monosomal karyotype (n=1,584) and with adverse cytogenetics without a monosomal karyotype (n=218), patients with a monosomal karyotype (n=188) were more likely not to achieve a complete remission with or without count recovery [odds ratio=2.85, 95% confidence interval (95%, CI): 2.10-3.88] and had shorter overall survival [hazard ratio, (HR)=2.44, 95% CI: 2.08-2.88]. There was no impact of the type of anthracycline or of the dose of cytarabine on outcomes in patients with a monosomal karyotype. Among monosomal karyo type patients who achieved a complete remission with or without count recovery, HLA-identical related donor availability was associated with longer survival from complete remission with or without count recovery (HR=0.59, 95% CI: 0.37-0.95). ClinicalTrials.gov identifiers: AML-10: NCT00002549; AML-12: NCT00004128. ispartof: HAEMATOLOGICA vol:104 issue:6 pages:1168-1175 ispartof: location:Italy status: published
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- 2019
15. Long-term follow-up of a trial comparing post-remission treatment with autologous or allogeneic bone marrow transplantation or intensive chemotherapy in younger acute myeloid leukemia patients
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Walter J.F.M. van der Velden, Laura Cannella, Theo de Witte, Jean-Pierre Marie, Maria Concetta Petti, Dario Ferrero, Edoardo La Sala, Sebastian Wittnebel, Paola Fazi, Roel Willemze, Marco Sborgia, Fabio Efficace, Sergio Amadori, Alberto Bosi, Marco Vignetti, Jean-Henri Bourhis, Francesco Fabbiano, Robert Zittoun, Frédéric Baron, Giovanni Martinelli, Petra Muus, Silvia Maria Trisolini, Stefan Suciu, and Constantijn J.M. Halkes
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Oncology ,medicine.medical_specialty ,Long term follow up ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Intensive chemotherapy ,Transplantation, Autologous ,Text mining ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Autogenous bone ,Online Only Articles ,Bone Marrow Transplantation ,Marrow transplantation ,business.industry ,Remission Induction ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Leukemia, Myeloid, Acute ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,business ,Follow-Up Studies - Abstract
Contains fulltext : 218286.pdf (Publisher’s version ) (Open Access)
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- 2020
16. Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study
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Laura Cannella, Roelof Willemze, Constantijn J.M. Halkes, Marian Stevens-Kroef, Umberto Vitolo, Petra Muus, Xavier Thomas, Jean-Pierre Marie, Bernardino Allione, Sergio Amadori, Giorgina Specchia, Silvia Maria Trisolini, Fabio Efficace, Jose E. Guimaraes, Paola Fazi, Jean-Henri Bourhis, Edoardo La Sala, Radovan Vrhovac, Felicetto Ferrara, François Lefrère, Liv Meert, Marco Vignetti, Francesco Di Raimondo, Theo de Witte, Stefan Suciu, Patrizia Chiusolo, Walter J.F.M. van der Velden, and Frédéric Baron
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Male ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Hematopoietic stem cell transplantation ,Gastroenterology ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Mitoxantrone / adverse effects ,Etoposide ,Leukemia, Myeloid, Acute / therapy ,Daunorubicin / administration & dosage ,Age Factors ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Idarubicin / adverse effects ,Induction Chemotherapy ,Hematology ,Middle Aged ,Allografts ,Leukemia, Myeloid, Acute ,Cytarabine / administration & dosage ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,Cytarabine / adverse effects ,medicine.medical_specialty ,Adolescent ,Anthracycline ,Idarubicin / administration & dosage ,Daunorubicin / adverse effects ,03 medical and health sciences ,Mitoxantrone / administration & dosage ,Internal medicine ,medicine ,Humans ,Idarubicin ,Etoposide / adverse effects ,Antineoplastic Combined Chemotherapy Protocols / administration & dosage ,Mitoxantrone ,business.industry ,Daunorubicin ,Induction chemotherapy ,Transplantation ,HLA matching, anthracycline, acute myeloid leukemia ,Leukemia, Myeloid, Acute / mortality ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Etoposide / administration & dosage ,business ,Follow-Up Studies ,030215 immunology - Abstract
Contains fulltext : 220443.pdf (Publisher’s version ) (Closed access) We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m(2) ), mitoxantrone (MXR, 12 mg/m(2) ), or idarubicin (IDA, 10 mg/m(2) ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.
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- 2020
17. Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD–mutated, relapsed or refractory AML
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Guy Gammon, Jean Pierre Marie, Denise Trone, Stuart L. Goldberg, Martin S. Tallman, Giovanni Martinelli, Gary J. Schiller, Mark J. Levis, Alexander E. Perl, Hagop M. Kantarjian, and Jorge E. Cortes
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Male ,Myeloid ,0301 basic medicine ,Gastrointestinal Diseases ,Salvage therapy ,Kaplan-Meier Estimate ,Cardiorespiratory Medicine and Haematology ,Biochemistry ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,Gene Duplication ,Cancer ,Oncogene Proteins ,Pediatric ,Leukemia ,Hematology ,Middle Aged ,Tandem Repeat Sequences ,6.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Female ,Drug ,Adult ,Pediatric Research Initiative ,medicine.medical_specialty ,Heart Diseases ,Childhood Leukemia ,Pediatric Cancer ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Immunology ,Antineoplastic Agents ,Acute ,QT interval ,Dose-Response Relationship ,Paediatrics and Reproductive Medicine ,Young Adult ,03 medical and health sciences ,Rare Diseases ,Refractory ,Clinical Research ,Quizartinib Dihydrochloride ,Internal medicine ,medicine ,Humans ,Benzothiazoles ,Dosing ,Fusion ,Protein Kinase Inhibitors ,Aged ,Quizartinib ,Salvage Therapy ,Surrogate endpoint ,business.industry ,Phenylurea Compounds ,Evaluation of treatments and therapeutic interventions ,Cell Biology ,Hematologic Diseases ,Transplantation ,030104 developmental biology ,fms-Like Tyrosine Kinase 3 ,chemistry ,business - Abstract
This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N = 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD-mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia's formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day.
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- 2018
18. Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials
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Gaetan de Schaetzen, Marco Vignetti, Roelof Willemze, Liv Meert, Theo de Witte, Giuseppe Leone, Giovanna Meloni, Boris Labar, Frédéric Baron, Stefan Suciu, Safaa M. Ramadan, Marian Stevens-Kroef, Jean Pierre Marie, Bob Löwenberg, Sergio Amadori, Petra Muus, Michael Lübbert, and Hematology
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Oncology ,Cancer Research ,medicine.medical_specialty ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,AML ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Overall survival ,Secondary Acute Myeloid Leukemia ,neoplasms ,Chemotherapy ,business.industry ,trials ,Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030220 oncology & carcinogenesis ,Cohort ,secondary ,business ,030215 immunology - Abstract
We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A, n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B, n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C, n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients &le, 60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p <, 0.001): 7.7% (95% CI: 1.3&ndash, 21.7%) for patients treated before 1990 (period 1: n = 26), 23.3% (95% CI: 17.1&ndash, 30.0%) for those treated between 1990 and 2000 (period 2: n = 188) and 36.5% (95% CI: 28.7&ndash, 44.3%) for those treated in 2000 or later (period 3: n = 153). In multivariate analysis, male gender (HR = 1.39, p = 0.01), WBC &ge, 25 ×, 109/L (HR = 2.00, p <, 0.0001), age 46-60 years (HR = 1.65, 0.001) and poor-risk cytogenetics (HR = 2.17, 0.0001) were independently associated with shorter OS, while being treated during period 2 (HR = 0.50, p = 0.003) or period 3 (HR = 0.43, p = 0.0008). Having received high-dose cytarabine (HD-AraC) (n = 48) in the induction chemotherapy (HR = 0.54, p = 0.012) was associated with a longer OS. In contrast, among patients >, 60 years of age (n = 502), the OS was dismal, and there was no improvement over time.
- Published
- 2020
19. Effectiveness of community‐based hypertension management on hypertension in the urban slums of Haiti: A mixed methods study.
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St Sauveur, Reichling, Sufra, Rodney, Jean Pierre, Marie Christine, Rouzier, Vanessa, Preval, Fabiola, Exantus, Serfine, Jean, Mirline, Jean, Josette, Forestal, Guyrlaine Pierre‐Louise, Fleurijean, Obed, Mourra, Nour, Ogyu, Anju, Malebranche, Rodolphe, Brisma, Jean Pierre, Deschamps, Marie M., Pape, Jean W., Sundararajan, Radhika, McNairy, Margaret L., and Yan, Lily D.
- Subjects
- *
COMMUNITY health workers , *PATIENT compliance , *BLOOD pressure , *HEALTH services accessibility , *COMMUNITY-based programs - Abstract
Hypertension is a leading contributor to mortality in low‐middle income countries including Haiti, yet only 13% achieve blood pressure (BP) control. We evaluated the effectiveness of a community‐based hypertension management program delivered by community health workers (CHWs) and physicians among 100 adults with uncontrolled hypertension from the Haiti Cardiovascular Disease Cohort. The 12‐month intervention included: community follow‐up visits with CHWs (1 month if BP uncontrolled ≥140/90, 3 months otherwise) for BP measurement, lifestyle counseling, medication delivery, and dose adjustments. Primary outcome was mean change in systolic BP from enrollment to 12 months. Secondary outcomes were mean change in diastolic BP, BP control, acceptability, feasibility, and adverse events. We compared outcomes to 100 age, sex, and baseline BP matched controls with standard of care: clinic follow‐up visits with physicians every 3 months. We also conducted qualitative interviews with participants and providers. Among 200 adults, median age was 59 years, 59% were female. Baseline mean BP was 154/89 mmHg intervention versus 153/88 mmHg control. At 12 months, the difference in SBP change between groups was −12.8 mmHg (95%CI −6.9, −18.7) and for DBP −7.1 mmHg (95%CI −3.3, −11.0). BP control increased from 0% to 58.1% in intervention, and 28.4% in control group. Four participants reported mild adverse events. In mixed methods analysis, we found community‐based delivery addressed multiple participant barriers to care, and task‐shifting with strong teamwork enhanced medication adherence. Community‐based hypertension management using task‐shifting with CHWs and community‐based care was acceptable, and effective in reducing SBP, DBP, and increasing BP control. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
20. Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15-60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials
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Constantijn J.M. Halkes, Xavier Thomas, Jean-Pierre Marie, François Lefrère, Marco Mancini, Anne Hagemeijer, Stefan Suciu, Giorgina Specchia, Sergio Amadori, Adriano Venditti, Joop H. Jansen, Michal Kicinski, Heiko Becker, Simona Sica, Petra Muus, Radovan Vrhovac, Roelof Willemze, Frédéric Baron, Theo de Witte, Marian Stevens-Kroef, and Giovanna Meloni
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Abnormal Karyotype ,Clonal heterogeneity ,Somatic evolution in cancer ,03 medical and health sciences ,Genetic Heterogeneity ,Young Adult ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,AML ,cytogenetic clonal heterogeneity ,acute myeloid leukemia ,Internal medicine ,medicine ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Humans ,Cytogenetic ,Randomized Controlled Trials as Topic ,Retrospective Studies ,Chromosome Aberrations ,Transplantation ,Hematology ,Clonal evolution ,Performance status ,Proportional hazards model ,business.industry ,Hazard ratio ,Myeloid leukemia ,General Medicine ,Middle Aged ,Prognosis ,Survival Analysis ,Leukemia, Myeloid, Acute ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Cytogenetic Analysis ,Female ,business ,Settore MED/15 - Malattie del Sangue - Abstract
The presence of cytogenetic clonal heterogeneity has been associated with poor prognosis in patients with acute myeloid leukemia (AML). Here, we reassessed this association. The study cohort consisted of all patients with an abnormal karyotype randomized in the EORTC/GIMEMA AML-10 and AML-12 trials. Abnormal karyotypes were classified as no subclones present (cytogenetic abnormality in a single clone), defined subclones present (presence of one to three subclones), and composite karyotypes (CP) (clonal heterogeneity not allowing enumeration of individual subclones). The main endpoints were overall survival (OS) and disease-free survival (DFS). Among 1291 patients with an abnormal karyotype, 1026 had no subclones, 226 at least 1 subclone, and 39 a CP. Patients with defined subclones had an OS similar to those with no subclones (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.88–1.26), but CP patients had a shorter OS (HR = 1.58, 95% CI 1.11–2.26). However, in a multivariate Cox model stratified by protocol and adjusted for age, cytogenetic risk group, secondary versus primary AML, and performance status, clonal heterogeneity lost its prognostic importance (HR = 1.10, 95% CI 0.91–1.32 for defined subclones versus no subclones; HR = 0.96, 95% CI 0.67–1.38 for CP versus no subclones). Also, the impact of having a donor on DFS was similar in the three clonal subgroups. In summary, in patients with cytogenetic abnormality, presence of subclones had no impact on OS. The dismal outcome in patients with a CP was explained by the known predictors of poor prognosis. Trial registration: AML-10: ClinicalTrials.gov identifier: NCT00002549, retrospectively registered July 19, 2004; AML12: ClinicalTrials.gov identifier: NCT00004128, registered January 27, 2003.
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- 2018
21. Phase 2b study of 2 dosing regimens of quizartinib monotherapy in
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Jorge E, Cortes, Martin S, Tallman, Gary J, Schiller, Denise, Trone, Guy, Gammon, Stuart L, Goldberg, Alexander E, Perl, Jean-Pierre, Marie, Giovanni, Martinelli, Hagop M, Kantarjian, and Mark J, Levis
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Adult ,Male ,Salvage Therapy ,Dose-Response Relationship, Drug ,Heart Diseases ,Oncogene Proteins, Fusion ,Gastrointestinal Diseases ,Phenylurea Compounds ,Antineoplastic Agents ,Kaplan-Meier Estimate ,Middle Aged ,Hematologic Diseases ,Leukemia, Myeloid, Acute ,Young Adult ,fms-Like Tyrosine Kinase 3 ,Tandem Repeat Sequences ,Gene Duplication ,Humans ,Female ,Benzothiazoles ,Protein Kinase Inhibitors ,Aged - Abstract
This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R)
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- 2018
22. Low-dose clofarabine in combination with a standard remission induction in patients aged 18-60 years with previously untreated intermediate and bad-risk acute myeloid leukemia or high-risk myelodysplastic syndrome: combined phase I/II results of the EORTC/GIMEMA AML-14A trial
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Marco Vignetti, Petra Muus, Roelof Willemze, Hans Pruijt, Giovanna Meloni, Sebastian Wittnebel, Adriano Venditti, Sergio Amadori, Dominik Selleslag, Liv Meert, Safaa M. Ramadan, Constantijn J.M. Halkes, Theo de Witte, Stefan Suciu, Frédéric Baron, and Jean Pierre Marie
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Oncology ,medicine.medical_specialty ,Myeloid ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Hematopoietic stem cell transplantation ,03 medical and health sciences ,Myelogenous ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Clofarabine ,Online Only Articles ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,Hematology ,medicine.disease ,Transplantation ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,business ,030215 immunology ,medicine.drug - Abstract
The prognosis of younger patients with intermediate/high risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndromes (MDS) remains unsatisfactory.[1][1]–[4][2] Clofarabine is a purine nucleoside analog that is highly active as a single agent in AML.[5][3] Furthermore, synergy
- Published
- 2017
23. Do ABC proteins still have a role to play in acute myeloid leukemia?
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Ollivier Legrand, Jean-Pierre Marie, Ruoping Tang, Pierre Hirsch, and Mohamad Mohty
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Myeloid leukemia ,Hematology ,Biology ,Molecular biology - Abstract
La resistance a la chimiotherapie est un probleme majeur dans le traitement des leucemies aigues myeloides (LAM). De multiples mecanismes aboutissant a la resistance ont ete decrits, et d’autres n’ont pas encore ete elucides. Parmi ces mecanismes, le role de la famille des proteines ABC est etudie depuis les annees quatre-vingt. Si le phenotype MDR (multidrug resistance) a d’abord ete relie a la seule proteine ABCB1 (PgP), de nombreux membres parmi les quarante-neuf de la famille ABC semblent impliques dans la chimioresistance. Dans cette revue, nous decrirons le role des proteines ABC dans l’hematopoiese normale et leucemique, et nous discuterons de leur valeur pour la prediction du pronostic des LAM. Nous discuterons egalement de leur valeur pronostique comparee a celles des marqueurs moleculaires comme FLT3, NPM1 ou CEBPA. Enfin, nous passerons en revue les differents essais cliniques incluant des modulateurs des proteines ABC, et nous discuterons des modalites possibles pour depasser la resistance liee aux proteines ABC.
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- 2014
24. Publié dans Hématologie vol. 11, n0 1, janvier-février 2005
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Joël Ceccaldi, Jean-Pierre Marie, Geneviève Marguerite, Dominique Bordessoule, Sylvie Gervaise, Dominique Jaulmes, Jean-Yves Cahn, H. Rochant, Philippe Casassus, Jean-Jacques Sotto, Philippe Colombat, Robert Zittoun, and Christian Bastard
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Hematology - Abstract
Les recommandations de la Societe de Reanimation en Langue Francaise (SRLF) [1], publiees en 2002, concernant les limitations et arrets de therapeutiques actives en reanimation adulte, sont a ce jour une initiative unique qui a modifie les pratiques professionnelles des services de reanimation. Dans un contexte different, de nombreuses situations posent au quotidien, dans les services d’hematologie, le probleme de la proportionnalite des soins et d’une eventuelle obstination deraisonnable, encore appelee communement acharnement therapeutique. En hematologie comme dans d’autres disciplines, cette conduite therapeutique peut etre cause de souffrance chez les malades, leurs familles et les soignants eux-memes, et souleve de graves problemes ethiques. C’est pourquoi le premier objectif du groupe Ethique de la Societe Francaise d’Hematologie (SFH), cree par son conseil d’administration en fevrier 2004, a ete de proposer a la discipline une reflexion et des recommandations. Ce texte a ete redige en s’inspirant du texte de la SRLF [1], des reflexions et de l’experience des membres du groupe et des donnees de la litterature. Il sera presente aux membres du conseil d’administration de la SFH et diffuse au sein de la discipline « hematologie ». Ce projet est apparu particulierement necessaire avec l’apparition de nouveaux textes legislatifs (en particulier la loi du 4 mars 2002), l’avis n° 60 du Comite Consultatif National d’Ethique du 27 janvier 2000 intitule « Fin de vie, arret de vie, euthanasie », la publication des recommandations de la Conference de consensus de l’ANAES des 14 et 15 janvier 2004 sur l’Accompagnement des patients en fin de vie et de leurs proches et la proposition de loi n° 1882 du 30 novembre 2004 relative aux droits des malades et a la fin de vie. Ce texte est propose comme une incitation a la reflexion plutot que comme une serie de recommandations qui s’ajouteraient aux textes officiels actuels ou en cours d’elaboration.
- Published
- 2014
25. Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial
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Roel Willemze, Mariam G Aslanyan, Sergio Amadori, Petra Muus, Leonie I. Kroeze, Evelyn Tönnissen, Pedro da Silva-Coelho, Jean-Pierre Marie, Stefan Suciu, Marion Massop, Theresia N. Koorenhof-Scheele, Erik W.A. Marijt, Adrian van der Heijden, Louis van de Locht, Saskia Langemeijer, Ellen Stevens-Linders, Giuseppe Saglio, Ruoping Tang, Bert A. van der Reijden, Patricia van Hoogen, Daniela Cilloni, Boris Labar, Theo de Witte, and Joop H. Jansen
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Male ,Oncology ,Pathology ,Myeloid ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Kaplan-Meier Estimate ,medicine.disease_cause ,DNA Methyltransferase 3A ,Chlorocebus aethiops ,TET2 expression ,Multicenter Studies as Topic ,Missense mutation ,DNA (Cytosine-5-)-Methyltransferases ,Prospective Studies ,RNA, Neoplasm ,Prospective cohort study ,Clinical Trials as Topic ,Mutation ,Hematology ,Gene Expression Regulation, Leukemic ,General Medicine ,Prognosis ,Isocitrate Dehydrogenase ,Neoplasm Proteins ,DNA-Binding Proteins ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,COS Cells ,5-Methylcytosine ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,Recombinant Fusion Proteins ,Transfection ,Dioxygenases ,Cytosine ,Young Adult ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Animals ,Humans ,RNA, Messenger ,Acute myeloid leukemia ,TET2 mutations ,business.industry ,Cancer ,medicine.disease ,Clinical trial ,business - Abstract
Item does not contain fulltext We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival.
- Published
- 2014
26. Attitudes of medical students towards men who have sex with men living with HIV: implications for social accountability.
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Dunbar, Willy, Alcide Jean-Pierre, Marie Colette, Raccurt, Christian, Pape, Jean William, and Coppieters, Yves
- Abstract
Objectives: To explore the attitudes that medical students in Haiti harbour toward Men who have Sex with Men living with HIV in order to better understand how stigma and other factors may impair healthcare, and to explore suggestions of opportunities in line with the values of social accountability. Methods: This study employed a qualitative design by using a grounded theory approach regarding the context of Haiti. We used purposive sampling to select the 22 research participants. In-depth interviews were conducted, audio-recorded, transcribed and analyzed using an inductive content analysis approach. Results: Although stigmatizing attitudes emerged through the findings, medical students expressed willingness to provide Men who have Sex with Men with adequate health services in relation to HIV care. Their expressions were based on the Men who have Sex with Men's comprehensive right to receive equitable care, the moral responsibility of healthcare professionals, their perception of health disparities and the HIV global risk reduction. Participants pointed out that the medical education curriculum did not consider sexual health and specificities of sexual minorities and suggested a more inclusive and socially accountable training based on equity and quality. Conclusions: The students expressed favourable attitudes regarding health services to Men who have Sex with Men even though some layered stigmatizing attitudes emerged through the discussions. They all lacked skills on how to handle health specificities of sexual minorities. These findings recommend a revision of the medical education curriculum in regard to social accountability principles. [ABSTRACT FROM AUTHOR]
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- 2020
- Full Text
- View/download PDF
27. Soluble endothelial protein C receptor (<scp>sEPCR</scp>) is likely a biomarker of cancer‐associated hypercoagulability in human hematologic malignancies
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Shah Soltan Mirshahi, Jean-Pierre Marie, Amu Therwath, Julia Pardo, Jeannette Soria, Pezhman Mirshahi, Sophie Dimicoli, Ruoping Tang, Elodie Ducros, Massoud Mirshahi, Anne-Marie Faussat, and Jdid Ibrahim
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Risk ,Cancer Research ,Receptors, Cell Surface ,Single-nucleotide polymorphism ,Biology ,protein C ,Polymorphism, Single Nucleotide ,Flow cytometry ,Antigens, CD ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Humans ,Thrombophilia ,Radiology, Nuclear Medicine and imaging ,thrombosis ,Original Research ,Retrospective Studies ,Endothelial protein C receptor ,Base Sequence ,medicine.diagnostic_test ,leukemia ,Endothelial Protein C Receptor ,Cancer ,Sequence Analysis, DNA ,medicine.disease ,Reverse transcription polymerase chain reaction ,Leukemia ,Oncology ,D-dimer ,Hematologic Neoplasms ,Immunology ,Biomarker (medicine) ,EPCR (CD201) ,Cancer Prevention ,Protein C ,medicine.drug - Abstract
Elevated plasma level of soluble endothelial protein C receptor (sEPCR) may be an indicator of thrombotic risk. The present study aims to correlate leukemia-associated hypercoagulability to high level plasma sEPCR and proposes its measurement in routine clinical practice. EPCR expressions in leukemic cell lines were determined by flow cytometry, immunocytochemistry, and reverse transcription polymerase chain reaction (RT-PCR). EPCR gene sequence of a candidate cell line HL-60 was also determined. Plasma samples (n = 76) and bone marrow aspirates (n = 72) from 148 patients with hematologic malignancies and 101 healthy volunteers were analyzed by enzyme-linked immunosorbent assay (ELISA) via a retrospective study for sEPCR and D-dimer. All leukemic cell lines were found to express EPCR. Also, HL-60 EPCR gene sequence showed extensive similarities with the endothelial reference gene. All single nucleotide polymorphisms (SNPs) originally described and some new SNPs were revealed in the promoter and intronic regions. Among these patients 67% had plasma sEPCR level higher than the controls (100 ± 28 ng/mL), wherein 16.3% patients had experienced a previous thrombotic event. These patients were divided into: group-1 (n = 45) with amount of plasmatic sEPCR below 100 ng/mL, group-2 (n = 45) where the concentration of sEPCR was between 100 and 200, and group-3 (n = 20) higher than 200 ng/mL. The numbers of thrombotic incidence recorded in each group were four, six, and eight, respectively. These results reveal that EPCR is expressed not only by a wide range of human malignant hematological cells but also the detection of plasma sEPCR levels provides a powerful insight into thrombotic risk assessment in cancer patients, especially when it surpasses 200 ng/mL.
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- 2012
28. Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups
- Author
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Paola Fazi, Franco Mandelli, Luigi Resegotti, Pietro Leoni, Sergio Amadori, Joseph Thaler, Jean-Pierre Marie, Marco Vignetti, Marysia Hengeveld, Theo de Witte, Giorgina Specchia, Matthias Karrasch, Bruno Rotoli, Robert Zittoun, Maria Concetta Petti, Enrica Morra, Guiseppe Fioritoni, Stefan Suciu, and Petra Muus
- Subjects
Myeloid ,Male ,International Cooperation ,Medical Oncology ,administration /&/ dosage/therapeutic use ,organization /&/ administration ,0302 clinical medicine ,Maintenance therapy ,Post-remission chemotherapy ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,polycyclic compounds ,Medicine & Public Health ,Societies, Medical ,0303 health sciences ,Leukemia ,Incidence (epidemiology) ,Translational research Immune Regulation [ONCOL 3] ,Age Factors ,Induction Chemotherapy ,Hematology ,General Medicine ,Middle Aged ,drug therapy ,3. Good health ,Europe ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Italy ,Oncology ,030220 oncology & carcinogenesis ,methods/standards ,Female ,Original Article ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Daunorubicin ,Acute ,Acute myeloid leukaemia ,methods/organization /&/ administration ,methods ,Maintenance Chemotherapy ,Young Adult ,03 medical and health sciences ,Translational research [ONCOL 3] ,Medical ,Internal medicine ,medicine ,Humans ,neoplasms ,Survival rate ,Adolescent, Adult, Age Factors, Antineoplastic Combined Chemotherapy Protocols ,administration /&/ dosage/therapeutic use, Consolidation Chemotherapy ,methods/standards, Europe, Female, Hematology ,methods/organization /&/ administration, Humans, Induction Chemotherapy ,methods, International Cooperation, Italy, Leukemia ,drug therapy, Maintenance Chemotherapy ,methods/standards, Male, Medical Oncology ,methods/organization /&/ administration, Middle Aged, Societies ,organization /&/ administration, Treatment Outcome, Young Adult ,030304 developmental biology ,business.industry ,Induction chemotherapy ,Consolidation Chemotherapy ,medicine.disease ,Surgery ,Cytarabine ,Societies ,business ,Settore MED/15 - Malattie del Sangue - Abstract
Item does not contain fulltext The most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group. 01 juni 2012
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- 2012
29. Double-delayed intensification paediatric protocol without radiotherapy is an efficient treatment in adult lymphoblastic lymphoma
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Zora Marjanovic, Simona Lapusan, Jean-Pierre Marie, Elise Corre, Ollivier Legrand, Pierre Hirsch, and Anne Vekhoff
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Cancer Research ,Pediatrics ,medicine.medical_specialty ,Poor prognosis ,business.industry ,Adult lymphoblastic lymphoma ,medicine.medical_treatment ,Lymphoblastic lymphoma ,Hematology ,General Medicine ,medicine.disease ,Lymphoma ,Radiation therapy ,Oncology ,hemic and lymphatic diseases ,medicine ,Young adult ,business ,Survival rate ,Rare disease - Abstract
Lymphoblastic lymphoma (LBL) is a rare disease associated with favourable prognosis in childhood but with poor prognosis in adults when treated with conventional non-Hodgkin lymphoma regimens. Improvements in long-term outcome have been made since the use of acute lymphoblastic leukaemia (ALL) regimens. We report here the feasibility of a double-delayed intensification paediatric protocol in 12 adult LBL patients. There were no relapses and no deaths, with a median follow-up of 4.7 years. Using the same protocol, overall survival was significantly longer in LBL patients versus ALL patients (100% vs 75%, p = 0.05). Overall tolerance was acceptable and better in ALL patients. We have shown the feasibility and the good results of using this paediatric protocol in LBL. Copyright © 2012 John Wiley & Sons, Ltd.
- Published
- 2012
30. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC
- Author
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Ruoping Tang, Ollivier Legrand, Fanny Fava, Jean Pierre Marie, Christophe Marzac, Jean-Yves Perrot, Pierre Hirsch, Dorota Jeziorowska, and Chantal Bernard
- Subjects
Adult ,Male ,NPM1 ,Adolescent ,Biology ,Young Adult ,hemic and lymphatic diseases ,CEBPA ,Biomarkers, Tumor ,Humans ,BAALC ,Aged ,Aged, 80 and over ,Nucleophosmin ,Acute leukemia ,Nuclear Proteins ,Myeloid leukemia ,Adult Acute Myeloid Leukemia ,Hematology ,Middle Aged ,Prognosis ,Molecular biology ,Neoplasm Proteins ,Leukemia, Myeloid, Acute ,fms-Like Tyrosine Kinase 3 ,Cytogenetic Analysis ,Fms-Like Tyrosine Kinase 3 ,CCAAT-Enhancer-Binding Proteins ,Cancer research ,ATP-Binding Cassette Transporters ,Female ,Original Articles and Brief Reports - Abstract
ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATP-binding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survival were age and ATP-binding cassette transporter activity. In conclusion, ATP-binding cassette transporter activity remains an independent prognostic factor, and could assist treatment decisions in patients with no nucleophosmin mutation and no fms-like tyrosine kinase 3 duplication.
- Published
- 2011
31. Outcome of 40 adults aged from 18 to 55 years with acute lymphoblastic leukemia treated with double-delayed intensification pediatric protocol
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Sophie Dimicoli, Jean-Pierre Marie, Elise Corre, Ollivier Legrand, Anne Vekhoff, Simona Lapusan, Pierre Hirsch, Bernard Rio, Stephanie Haiat, and Zora Marjanovic
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Dose-Response Relationship, Drug ,business.industry ,Lymphoblastic Leukemia ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Gastroenterology ,Young Adult ,Oncology ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Feasibility Studies ,Humans ,Female ,In patient ,business - Abstract
Adolescents ALL have a better outcome when treated with pediatric protocol compared to adult protocol. We have tested the feasibility of pediatric protocol to treat 40 consecutive adults ALL. DFS and OS were 73 ± 7%, and 72 ± 7%, and were significantly longer in patients under 40 yo (81 ± 9% vs 51 ± 15%, p = 0.05 [DFS] and 83 ± 7.8% vs 45 ± 15%, p = 0.003 [OS], respectively) or cortico/chemo-sensitive (86 ± 9% vs 36 ± 16%, p = 0.001 [DFS] and 95 ± 4.4% vs 28 ± 13%, p < 0.0001 [OS]) than in other patients. Overall tolerance was acceptable. We have shown the feasibility of using this unmodified pediatric protocol to treat adult with ALL up to 40 years.
- Published
- 2011
32. Long-term imatinib maintenance therapy for adult Philadelphia positive acute lymphoblastic leukemia
- Author
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Christophe Marzac, Mohamad Mohty, Jean-Pierre Marie, Ollivier Legrand, Stéphanie Guillet, and Pierre Hirsch
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Oncology ,Cancer Research ,medicine.medical_specialty ,Philadelphia Chromosome Positive ,business.industry ,Lymphoblastic Leukemia ,Philadelphia positive ,Imatinib ,Hematology ,Natural history ,Maintenance therapy ,hemic and lymphatic diseases ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Imatinib, approved more than 10 years ago, has significantly modified the natural history of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph ALL). In adults, 15–30% of patients wi...
- Published
- 2014
33. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial
- Author
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Harald Biersack, Jean-Pierre Marie, Stefan Suciu, Joop H. Jansen, Petra Muus, Alois Gratwohl, Pierre W. Wijermans, Dominik Selleslag, Roel Willemze, Anne Hagemeijer, Eva Hellström-Lindberg, Tibor Kovacsovics, Sergio Amadori, Amin Belhabri, Gert J. Ossenkoppele, Harry C. Schouten, Augustin Ferrant, Michel Delforge, Guido Kobbe, Theo de Witte, Interne Geneeskunde, and RS: GROW - School for Oncology and Reproduction
- Subjects
Oncology ,medicine.medical_specialty ,autologous stem cell transplantation ,medicine.medical_treatment ,Medizin ,Autologous stem-cell transplantation ,allogeneic stem cell transplantation ,Immune Regulation [NCMLS 2] ,Translational research [ONCOL 3] ,Internal medicine ,Medicine ,Survival analysis ,Chemotherapy ,business.industry ,intensive chemotherapy ,Myelodysplastic syndromes ,Hazard ratio ,Hematology ,cytogenetic characteristics ,medicine.disease ,myelodysplastic syndromes ,Surgery ,Transplantation ,Leukemia ,Cytarabine ,Original Article ,secondary acute myeloid leukemia ,business ,medicine.drug - Abstract
Contains fulltext : 87519.pdf (Publisher’s version ) (Open Access) BACKGROUND: Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old. DESIGN AND METHODS: We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine. RESULTS: The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49-1.35) for survival and of 0.67 (95% CI, 0.42-1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22-1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22-1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40-3.42) and that for disease-free survival was 1.02 (99% CI, 0.40-2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65-2.27) for survival and 1.02 (95% CI, 0.56-1.85) for disease-free survival. CONCLUSIONS: Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy. 01 oktober 2010
- Published
- 2010
34. Platform presentations
- Author
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Jaime Pereda, Gen Niimi, Jagat Mohini Kaul, Sabita Mishra, Babita Pangtey, Daniele Peri, Vincenza Cannella, Giovanni Peri, A. Valentino, Francesco Li Volsi, Rosaria Lo Verde, E. Russo, A. Sciuto, Annalisa Sunseri, Giuseppe Modica, Gianpiero Gravante, Seok Ling Ong, Matthew Metcalfe, David Lloyd, Ashley Dennison, Veronica Macchi, Andrea Porzionato, Anna Parenti, Raffaele De Caro, Kawthar I. F. Al-Harmni, Zohair I. F. Rahemo, Hussain I. A. Al-Khan, Vedat Bakan, Gulen Demirpolat, Mahmut Bozkurt, Yakup Gumusalan, Niyazi Acer, Mehmet Demir, Hulusi Taskoparan, Akcan Akkaya, Birdal Yildirim, Mehmet Camurdanoglu, Gul Guven, Hilmi Ozden, Sahin Kabay, Cengiz Ustuner, Dilek Burukoglu, Derya Ustuner, Irfan Degirmenci, Fahrettin Akyuz, Neslihan Tekin, Fulya Kucuk, Firdevs Gurer, M. Cengiz Ustuner, Davut Ozbag, Mesut Ozkaya, Harun Ciralik, Fatma Inanc Tolun, Fatih Yuzbasioglu, Seda Arslan, Ghazaleh Moshkdanian, Fatemeh Pouya, Amirmahdi Nematollahi-Mahani, Seyed Noureddin Nematollahi-Mahani, Ralph Ger, Jeremy Nikfarjam, Kathy Dooley, Shuwei Liu, Zhenping Li, Xiangtao Lin, Haiwei Meng, Cheng Liu, Lei Feng, Min Suk Chung, Dong Sun Shin, Eric Havet, Anne-Claire Dujardin, Fabrice Duparc, Pierre Freger, Anitha Oommen, Christoph Stosch, Jürgen Koebke, Stefan Herzig, Adam Jqbal, Paul Gazzani, Tim Rattay, Birgit Fruhstorfer, Anil Vohrah, Richard M. Wellings, Stephen Brydges, Gregory R. Smith, Jamie Roebuck, Peter H. Abrahams, Vaclav Baca, Michal Otcenasek, Filip Svatos, Tereza Smrzova, Robert Grill, David Kachlik, Jan Skubal, Valer Dzupa, Alena Doubkova, Ivo Klepacek, Josef Stingl, Muddathir Ali, Yahya Bedir, Günther Weber, Karim Malek, Amos Patrick, Brent Rochambeau, Phil Knickelbein, Da-Yae Choi, Mi-Sun Hur, Kwan-Hyun Youn, Kyung-Seok Hu, Hee-Jin Kim, Fadullah Aksoy, Yavuz Selim Yildirim, Orhan Ozturan, Hurtan Acar, Hasan Demirhan, Bayram Veyseller, Jean Michel Prades, Andrei Timoshenko, Alexander Asanau, Marie Gavid, Christian Martin, Benoit Ayestaray, Isabelle Auquit-Auckbur, Pierre-Yves Millez, Burcu Ercakmak, Alp Bayramoglu, Hakan Ozsoy, Deniz Demiryurek, Eray Tuccar, Keiichi Akita, Kumiko Yamaguchi, Atsuo Kato, Tomoyuki Mochizuki, Julien Beldame, Jean-Philippe Mure, Benjamin Lefebvre, David M. Lloyd, K. J. Karmand, M. G. Norwood, Aysin Kale, Ozcan Gayretli, Adnan Ozturk, Ilke Ali Gurses, Ahmet Usta, Kayihan Sahinoglu, Gokhan Kaynak, Mustafa Bilgili, Isik Akgun, Tahir Ogut, Mehmetcan Unlu, Ibrahim Uzun, Biagio Valentino, Elvira Farina, Tomoyasu Kato, Stoyan Pavlov, Maria Grosheva, Andrey Irintchev, Doychin Angelov, Tulin Sen, Ali Firat Esmer, S. Tuna Karahan, Benoit Delas, Jean Pierre Marie, Jean Christophe Sabourin, Anna Hebda, Rachel Claire Aland, Nihal Apaydin, Alparslan Apan, Aysun Uz, Ayhan Comert, Mehmet Arslan, Halil Ibrahim Acar, Mevci Ozdemir, Alaittin Elhan, Ibrahim Tekdemir, R. Shane Tubbs, Ayhan Attar, Hasan Caglar Ugur, Zeliha Fazliogullari, Ismihan Ilknur Uysal, Ahmet Kagan Karabulut, Nadire Unver Dogan, Muzaffer Seker, Neslihan Cankara, Mehmet Ali Malas, Emine Hilal Evcil, Aysegul Firat, Mine Erbil, Figen Kaymaz, Sinan Yuruker, Semiha Sen, Mina Tadjalli, Seid Reza Ghazi, Paria Parto, Seyed Reza Ghazi, Ceren Gunenc Beser, Musturay Karcaaltincaba, H. Hamdi Celik, Ruhgun Basar, Serpil Cilingiroglu, Cemal Ozbakir, Kenan Kose, Suleyman Tuna Karahan, Gulnur Ozguner, Osman Sulak, Irwin Best, Radovan Turyna, Ismail Malkoc, Huseyin Karagoz, Bilal Firat Alp, Cemal Gundogdu, Samih Diyarbakir, Firas Ghazi, Panagiotis Karanis, Sayee Rajangam, Preetha Tilak, Rema Devi, Bita Seifi, Naeem Earfani Majd, Mehran Dorstghol, Negar Niakan, Behpour Yousefi, Nooshin Bromand, Saeed Haghighi, Majid Malekzadeh Shafaroudi, Craig Daly, John Chris McGrath, Reza Ahadi, Mehrdad Bakhtiary, Mohammad Taghi Joghataei, Mehdi Mehdizadeh, Samideh Khoei, Mohsen Marzban, Parvin Salehinejad, Zahra Torshizi, Maryam Mohit, Nourjahan Banou Alithan, Ali Adulmanaf, Omar Abdulrahman, Seyed Adel Moallem, Bibi Ezzat Hosseini, Mohammad Afshar, Mohammad Mehdi Hasanzadeh Taheri, Javad Hami, Mohammad Hossein Davari, Saeid Kalbasi, Noroz Najafzade, Malihe Nobakht, Manoochehr Safari, Sara Asalgoo, Nahid Rahbar Roshandel, Mohamad Taghi Joghataeei, Mehrdad Bakhtiari, Farid Safar, Negin Salamat, Naeem Alboghobeish, Mahmood Hashemitabar, Mehrzad Mesbah, Ewa Biegaj, Tymon Skadorwa, Robert Kapolka, Bogdan Ciszek, Maria Piagkou, Giannoulis Piagkos, Vassiliki Kouki Aikaterini, Stergios Douvetzemis, Panagiotis Skandalakis, Sophia Anagnostopoulou, Mohamed Rashid Haffajee, Mohamed Adoobaker Ebrahim, J. W. Smith, Peter Osmotherly, Darren Rivett, Susan Mercer, Bin Yue, Dai-Soon Kwak, Yong-Seok Nam, Je-Hun Lee, U-Young Lee, Xiaochun An, Mi-Sun Lee, Seung-Ho Han, Ahmet Songur, Olcay Eser, Ozan Alkoc, Muhsin Toktas, Veli Caglar, Tuncay Kaner, Mehmet Tugrul Yilmaz, Serter Gumus, Isinman Ilknur Uysal, Yahya Paksoy, Mahinur Ulusoy, Mehmet Bulent Balioglu, Koray Savran, Gazi Zorer, Hitomi Fujishiro, Takeshi Muneta, Kenji Sato, Joël Vernois, Patrice Mertl, Bo Sun, Ge Haitao, Tang Yuchun, Zhonghe Zhang, Gaojun Teng, Hequn Geng, Taifei Yu, Umit S. Sehirli, Ural Verimli, Emel Ulupinar, Ferruh Yucel, Lia Neto, Edson Oliveira, Daniel Neto, Hugo Martins, Inácio Reis, Francisco Correia, António Goncalves Ferreira, Joana Regala, Paula Fernandes, Joana Teixeira, G. Nilufer Yonguc, M. Bulent Ozdemir, Vural Kucukatay, Melike Sahiner, Raziye Kursunluoglu, Esat Adiguzel, Ilgaz Akdogan, Yusuf Yilmaz, Melek Bor Kucukatay, Gulten Erken, M. Ayberk Kurt, Ilker M. Kafa, Murat Uysal, Sinan Bakirci, Suraj Prakash, Mahindra Kumar Anand, Meena Verma, Mohsen Basiri, Ronald Doucette, Yuchun Tang, Lingzhong Fan, Mehmet Dumlu Aydin, Canan Atalay, Sare Altas, Ednan Bayram, Bunyami Unal, Sahin Asian, Georg Feigl, Friedrich Anderhuber, Rainer Rienmuller, Jean Phillippe Guyot, Jean H. D. Fasel, Izabel Kos, Oguz Aslan Ozen, Mustafa Sarsilmaz, Gunnar Grant, Mohammad Reza Nourani, Zahra Jamali, Hamid Reza Taghipour, Yuji Owada, Mohammad Ali Khalili, Ben R. Clower, Morteza Anvari, Fatemeh Sadeghian, Farzaneh Fesahat, Seyd Mohsen Miresmaili, Bagher Pourheydar, Mohammad Taghi Joghataeei, Vahid Pirhajati, Abolfazl Faghihi, Fereshteh Mehraeen, S. Saeed Seyed Jafari, Abbas Aliaghaei, S. Noureddin Nematollahi-Mahani, Vahid Sheibani, Majid Asadi, Gholam Reza Kaka, Taki Tiraihi, Karol Budohoski, Jacek Kunicki, Ulrike Pilsl, Can Pelin, Baris Ozener, Ayla Kurkcuoglu, Ragiba Zagyapan, Anna Zurada, Jerzy Gielecki, Hakan Ay, Bruno Grignon, Frederic Walter, Toufik Batch, Horatiu Varlam, Iulian Iopincariu, Mehdi Benkhadra, Francois Lenfant, Pierre Trouilloud, Manuel Kastner, and Likar Rudolf
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Entrapment ,business.industry ,Medicine ,Radiology, Nuclear Medicine and imaging ,Surgery ,Anatomy ,business ,Radial nerve ,Pathology and Forensic Medicine - Published
- 2009
35. Vasculogenic mimicry of acute leukemic bone marrow stromal cells
- Author
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Rémi Varin, P. Mirshahi, G Kalantar, Massoud Mirshahi, Jean-Pierre Marie, Calandini Oa, C Marzac, Jeannette Soria, Claudine Soria, L. Vincent, A Berthaut, and Arash Rafii
- Subjects
rho GTP-Binding Proteins ,Cancer Research ,medicine.medical_specialty ,Stromal cell ,Angiogenesis ,CD34 ,Biology ,Phosphatidylinositol 3-Kinases ,Bone Marrow ,Internal medicine ,medicine ,Humans ,Vasculogenic mimicry ,Insulin-Like Growth Factor I ,Matrigel ,Leukemia ,Neovascularization, Pathologic ,Hematology ,Chemokine CXCL12 ,medicine.anatomical_structure ,Endocrinology ,Oncology ,Case-Control Studies ,Acute Disease ,Neoplastic Stem Cells ,Cancer research ,Picropodophyllin ,Bone marrow ,Stromal Cells ,Stem cell ,Signal Transduction - Abstract
Angiogenesis is thought to be involved in the development of acute leukemia (AL). We investigated whether bone marrow stromal cells (BMSCs) derived from stem cells might be responsible for the increase in microvascular density (MVD), and compared 13 bone marrow samples from AL patients with 23 samples from patients in complete remission (controls). We demonstrated that AL-derived BMSC secreted more insulin growth factor-1 (IGF-1) and SDF-1alpha than controls. In addition, in contrast to normal adherent BMSCs, adherent BMSCs derived from CD133+/CD34+ stem cells from AL patients were able to form capillary-like structures ('vasculogenic mimicry') on Matrigel. The increase in vasculogenic mimicry occurred through PI3 kinase and rho GTPase pathway as inhibitors of these signaling pathways (wortmannin and GGTI-298, respectively) were able to reduce or prevent capillary tube formation. In normal BMSC, addition of exogenous IGF-1 generated capillary-like tubes through the same pathway as observed spontaneously in AL-derived BMSC. The involvement of IGF-1 in the mimicry process was confirmed by the addition of a neutralizing antibody against IGF-1R or a IGF-1R pathway inhibitor (picropodophyllin). In conclusion, AL-derived BMSC present functional abnormalities that may explain the increase in MVD in the bone marrow of AL patients.
- Published
- 2009
36. Fully functional NK cells after unrelated cord blood transplantation
- Author
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Vivien Béziat, Dominique Bories, Z. Marjanovic, Patrice Debré, Jean-Pierre Marie, Helene Trebeden-Negre, Baptiste Hervier, A. Boudifa, Françoise Norol, Bernard Rio, Madalina Uzunov, J P Vernant, Simona Lapusan, Vincent Vieillard, Nathalie Dhedin, and Stéphanie Nguyen
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Graft vs Leukemia Effect ,Biology ,Umbilical cord ,Immunophenotyping ,Natural killer cell ,Blood cell ,Young Adult ,Internal medicine ,medicine ,Humans ,Cytotoxicity ,Hematology ,Umbilical Cord Blood Transplantation ,Histocompatibility Testing ,Middle Aged ,Phenotype ,Tissue Donors ,Hematopoiesis ,Killer Cells, Natural ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Hematologic Neoplasms ,Immunology ,Female ,Cord Blood Stem Cell Transplantation ,Stem cell - Abstract
Promising results of umbilical cord blood transplantation (UCBT) from unrelated donors have been reported in patients with hematologic disorders. These transplants, having potential to trigger beneficial donor-versus-recipient natural killer (NK) cell-mediated alloreaction, we have conducted the first extensive analysis of the phenotypic and functional properties of NK cells after UCBT. NK cells from 25 patients with high-risk hematologic malignancies were compared with cells derived from both healthy adult and CB cells. We found that following UCBT, NK cells display not only some phenotypic features associated with maturity but also unique characteristics that make them fully functional against leukemic blasts. We propose that this full functionality of alloreactive donor-derived NK may drive graft-versus-leukemia reactions after UCBT.
- Published
- 2009
37. Over-expression of cyclin D1 in chronic B-cell malignancies with abnormality of chromosome 11q13
- Author
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Sylvie Ramond, Jean-Pierre Marie, Anne-Marie Faussat, Florence Ajchenbaum-Cymbalista, Alain Delmer, Robert Zittoun, and Ruoping Tang
- Subjects
medicine.medical_specialty ,Pathology ,Lymphoma, B-Cell ,Chronic lymphocytic leukemia ,Apoptosis ,Trisomy ,Chromosomal translocation ,Biology ,Translocation, Genetic ,Lymphoplasmacytic Lymphoma ,Cyclin D1 ,Cyclins ,hemic and lymphatic diseases ,medicine ,Humans ,In Situ Hybridization ,Aged ,Chromosome Aberrations ,Oncogene Proteins ,Chromosomes, Human, Pair 11 ,Cytogenetics ,Karyotype ,Hematology ,Gene rearrangement ,Middle Aged ,Blotting, Northern ,Flow Cytometry ,medicine.disease ,Lymphoma ,Female - Abstract
Accurate identification of B-cell chronic malignancies is sometimes uncertain, despite careful cytologic and immunophenotypic evaluation. Cytogenetics and molecular biology studies may therefore prove useful, because some of these disorders are associated with non-random abnormalities, such as the t(11;14)(q13;q32) translocation and bcl-1 rearrangement mainly observed in mantle-cell lymphoma (MCL). We studied the expression of cyclin D1 in malignant lymphoid cells from the peripheral blood of 32 patients with various B-cell chronic lymphoproliferative disorders, using Northern blot (NB) and RNA in situ hybridization (ISH). Cytogenetic analysis was informative in 18 cases, and most of the missing karyotype data were from typical B-CLL cases where a t(11;14) is unlikely to be found. Over-expression of cyclin D1 mRNA was observed by both NB and ISH in four samples (MCL; two cases; lymphoplasmacytic lymphoma: one case, unclassified B-cell chronic disorder: one case). In each of these cases there was an abnormality of chromosome 11q13, either a t(11;14)(q13;q32) translocation (three cases) or a del(11)(q13) without evidence of chromosome 14 involvement (one case). Cytogenetic and gene rearrangement studies are not available in all institutions and have some technical pitfalls. Because of its close association with bcl-1 rearrangement and/or t(11;14), the demonstration of cyclin D1 mRNA over-expression either by NB, or, more conveniently, by ISH, may represent additional information which could be of help for the identification of B-cell malignancies.
- Published
- 2008
38. Endothelial cell markers' kinetics following umbilical cord blood transplantation
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Jean-Pierre Marie, Anna D. Petropoulou, Samama M, Francine Rendu, Pezhman Mirshahi, Bernard Rio, Jeannette Soria, Ismail Elalamy, Département d'Hématologie et Oncologie Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation cellulaire, dynamique circulatoire et athérosclérose précoce (SCDCAP), Centre National de la Recherche Scientifique (CNRS), Serv. Hématologie Biologie Hôtel Dieu, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Serv. Hématologie Biologie Hôp. Tenon, Assistance publique - Hôpitaux de Paris (AP-HP), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Signalisation cellulaire, dynamique circulatoire et athérosclérose précoce ( SCDCAP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Cord Blood Stem Cell Transplantation ,Thrombomodulin ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,medicine ,[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology ,ComputingMilieux_MISCELLANEOUS ,biology ,Umbilical Cord Blood Transplantation ,business.industry ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,3. Good health ,Endothelial stem cell ,Transplantation ,Vascular endothelial growth factor A ,surgical procedures, operative ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Peripheral Blood Stem Cell Transplantation ,sense organs ,business ,030215 immunology - Abstract
Hyper acute and acute vascular rejections represent the major problem in organ xeno-transplantation. According to the humoral theory of transplantation, acute and chronic rejections of allografts a...
- Published
- 2008
39. Endothelial protein C receptor gene 6936A/G single-nucleotide polymorphism as a possible biomarker of thrombotic risk in acute myeloid leukemia
- Author
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Hamda Althawadi, Jean Pierre Marie, Halema Alfarsi, Ruoping Tang, Julia Pardo, Eva‑Maria Huessler, Shahsoltan Mirshahi, Jeannette Soria, Fanny Fava, Ibtissem Ghedira, Samaher Besbes, Massoud Mirshahi, and Thomas Galtier
- Subjects
Cancer Research ,Endothelial protein C receptor ,Oncogene ,business.industry ,Myeloid leukemia ,Single-nucleotide polymorphism ,Articles ,Molecular medicine ,Oncology ,Genotype ,Immunology ,Medicine ,SNP ,business ,Protein C ,medicine.drug - Abstract
Protein C (PC) is a natural anticoagulant, which interacts with the endothelial PC receptor (EPCR). EPCR single-nucleotide polymorphism (SNP) 6936A/G results in high levels of a free soluble form of EPCR (sEPCR) and may affect the risk of coagulation. The objective of this study was to assess whether the 6936A/G SNP of the EPCR gene is involved in the procoagulant activity displayed by hematological malignancies. EPCR 6936A/G polymorphism analysis was performed in 205 patients with hematological malignancies and in 63 healthy controls. All the subjects were genotyped for the EPCR 6936A/G SNP (AA, AG and GG genotypes). The 6936A/G polymorphism distribution was similar between healthy donors and patients. The association between EPCR 6936A/G SNP and thrombosis was investigated in 110 patients. The disease-wise break-up revealed that 55 of the patients suffered from acute myeloid leukemia (AML). In AML patients, the incidence of thrombosis was 28.3% and significantly higher in the 6936AG compared with that in the 6936AA genotype (50 vs. 22%, respectively). In conclusion, this study revealed a significant association of the 6936AG genotype of EPCR with thrombotic events in AML. Therefore, the presence of the 6936AG genotype in AML patients may be considered as a risk indicator of thrombosis.
- Published
- 2015
40. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies
- Author
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Franco Mandelli, Jean-Pierre Marie, Marco Vignetti, Petra Muus, Eva Hellström-Lindberg, Carlo Aul, Theo de Witte, Dominik Selleslag, Boris Labar, Roel Willemze, Sergio Amadori, Songuel Cakmak-Wollgast, Stefan Suciu, M. Oosterveld, Amin Belhabri, Augustin Ferrant, Ulrich Jehn, Ulrich Germing, Michel Delforge, and Uwe Hess
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Myeloid ,Adolescent ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Severity of Illness Index ,Young Adult ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Secondary Acute Myeloid Leukemia ,Humans ,Survival rate ,Hematology ,Performance status ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,General Medicine ,Middle Aged ,medicine.disease ,Europe ,Survival Rate ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Treatment Outcome ,Myelodysplastic Syndromes ,Immunology ,Female ,business - Abstract
Item does not contain fulltext High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-specific prognostic factors and to develop prognostic scores for both patient groups. A total of 692 patients in the EORTC/GIMEMA AML-10 study and 289 patients in the CRIANT study received identical remission-induction and consolidation treatment. Estimated 5-year survival rate was 34 % in the AML-10 versus 27 % in the CRIANT study, and estimated disease-free survival was 40 % versus 28 %, respectively. In multivariate analysis, cytogenetic characteristics, white blood count, and age appeared prognostic for survival in both studies. French-American-British (FAB) subtype and performance status were prognostic in the AML-10 study only, whereas number of cytopenias and duration of antecedent hematologic disorder >6 months were prognostic in the CRIANT study only. The prognostic scores distinguish three groups with a 5-year survival rate of 54, 38, and 19 % in the AML-10 study versus 69, 37, and 5 % in the CRIANT study. The prognostic value of these scores has been validated on two external series. The new scoring systems form a practical tool to predict the outcome of individual MDS and AML patients treated with intensive antileukemic therapy.
- Published
- 2015
41. Flt3 Internal Tandem Duplication and P-Glycoprotein Functionality in 171 Patients with Acute Myeloid Leukemia
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Anne-Marie Faussat, Jean-Pierre Marie, Ruoping Tang, Ors'Anton Calendini, Ollivier Legrand, Christophe Marzac, Nicole Casadevall, Irène Teyssandier, and Jean-Yves Perrot
- Subjects
Adult ,Oncology ,FLT3 Internal Tandem Duplication ,Cancer Research ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Adolescent ,endocrine system diseases ,medicine.medical_treatment ,Biology ,Targeted therapy ,Risk Factors ,Gene Duplication ,Internal medicine ,polycyclic compounds ,medicine ,Humans ,Aged ,Aged, 80 and over ,integumentary system ,Performance status ,Remission Induction ,Cytogenetics ,Myeloid leukemia ,Cancer ,Adult Acute Myeloid Leukemia ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,body regions ,Treatment Outcome ,fms-Like Tyrosine Kinase 3 ,Leukemia, Myeloid ,Tandem Repeat Sequences ,Acute Disease ,Cytogenetic Analysis ,Multivariate Analysis ,Fms-Like Tyrosine Kinase 3 ,Immunology ,psychological phenomena and processes ,Follow-Up Studies - Abstract
Purpose: Patients with adult acute myeloid leukemia (AML) with intermediate cytogenetics remain a heterogeneous group with highly variable individual prognoses. New molecular markers could help to refine cytogenetic stratification. Experimental Design: We assessed P-glycoprotein (Pgp) activity and Flt3 internal tandem duplication (ITD+) because of their known prognostic value and because they might lead to targeted therapy. We did a multivariate analysis on 171 patients with adult AML treated in the European Organization for Research and Treatment of Cancer protocols. Results: ITD+ and high Pgp activity (Pgp+) were found in 26 of 171 (15%) and 55 of 171 (32%) of all patients, respectively. ITD and Pgp activities were negative in 94 of 171 (55%, Pgp−ITD− group), mutually exclusive in 73 of 171 (43%, Pgp−ITD+ and Pgp+ITD− groups), and only 4 of 171 (2%, Pgp+ITD+ group) patients were positive for both. In multivariate analyses, Pgp+ITD+ (P < 0.0001) and age (P = 0.0022) were independent prognostic factors for the achievement of complete remission (CR). Overall survival (OS), CR achievement (P < 0.0001), WHO performance status (P = 0.0007), and Pgp+ITD+ status (P = 0.0014) were also independent prognostic factors. In 95 patients with intermediate cytogenetics, the CR rates of ITD+ patients were 40% versus 62% for ITD− (P = 0.099) and 41% versus 67% (P = 0.014) for Pgp+ versus Pgp− patients. In the Pgp−ITD− group (41 of 95), CR rates were 70% versus 44% for others (P = 0.012), OS achieved 48% versus 16% (P < 0.0001) and disease-free survival was 56% versus 27% (P = 0.024), respectively. Furthermore, the OS curves of the intermediate cytogenetics-Pgp−ITD− group were not significantly different from the favorable cytogenetic group. Conclusion: Flt3/ITD and Pgp activity are independent and additive prognostic factors which provide a powerful risk classification that can be routinely used to stratify the treatment of patients with intermediate cytogenetic AML. ITD+ and Pgp+ patients should be considered for targeted therapy.
- Published
- 2006
42. Prospective Evaluation of a Polymerase Chain Reaction–ELISA Targeted toAspergillus fumigatusandAspergillus flavusfor the Early Diagnosis of Invasive Aspergillosis in Patients with Hematological Malignancies
- Author
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Martine Florent, Jean-Pierre Marie, Anne Vekhoff, Sandrine Katsahian, Anne Bouvet, Bernard Rio, Muriel Cornet, and Vincent Levy
- Subjects
medicine.medical_specialty ,Pathology ,Enzyme-Linked Immunosorbent Assay ,Aspergillus flavus ,Computed tomography ,Aspergillosis ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Gastroenterology ,law.invention ,Aspergillus fumigatus ,Mannans ,Galactomannan ,chemistry.chemical_compound ,Predictive Value of Tests ,law ,Positive predicative value ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,DNA, Fungal ,Polymerase chain reaction ,Mycosis ,biology ,medicine.diagnostic_test ,Galactose ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,Early Diagnosis ,Infectious Diseases ,Molecular Diagnostic Techniques ,chemistry ,Hematologic Neoplasms - Abstract
Background. Current laboratory and radiological methods for diagnosis of invasive aspergillosis (IA) lack sensitivity and specificity. Methods. We prospectively evaluated the diagnostic value of twice-weekly screening for circulating Aspergillus fumigatus and A. flavus DNA with a polymerase chain reaction–enzyme-linked immunosorbent assay (PCR-ELISA). Results. Among the 201 adult patients with hematological malignancies who were included in the study, 55 IA cases were diagnosed. On the basis of the analysis of 1205 serum samples from 167 patients, the sensitivity, specificity, and positive and negative predictive values of the PCR-ELISA for proven and probable IA cases were 63.6%, 89.7%, 63.6%, and 89.7%, respectively, when samples with 2 consecutive positive results were used. The use of a combination of the PCR-ELISA and a galactomannan (GM) assay increased the sensitivity to 83.3%, increased the negative predictive value to 97.6%, and decreased the specificity to 69.8%. In most patients with IA, PCR-ELISA positivity anticipated or was simultaneous with the initiation of antifungal therapy, the abnormalities found by computed tomography, the mycological/histological diagnosis, and the GM positivity. Overall, 56.3% of the patients had at least 1 positive sample, and the false single-positive rate was 44.8%. Conclusions. In addition to serial screening for GM antigenemia and radiological surveillance, PCR-ELISA may improve the rates of early diagnosis of IA and the management of patients with hematological malignancies.
- Published
- 2006
43. Mécanismes de résistance aux agents cytostatiques
- Author
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Christophe Marzac, Jean-Pierre Marie, and Ollivier Legrand
- Subjects
Chemistry ,Hematology ,Molecular biology - Abstract
Resume Les mecanismes de resistance des cellules tumorales sont le plus souvent multifactoriels. Le mieux etudie est le phenotype « MDR », pour multi-drug resistance , qui interesse des cytostatiques majeurs (anthracyclines, vinca-alcaloides, epipodophyllotoxines). Il est du a la presence de proteines de transport (proteines ABC) capables d'effluer ces cytostatiques, tous d'origine naturelle (xenobiotiques). La P-gp, la plus etudiee de ces proteines, a une valeur pronostique independante dans la sensibilite au traitement des leucemies aigues myeloblastiques, ce qui a conduit a des essais de « modulation » de la P-gp dans cette maladie. La quinine, la ciclosporine, le PSC833 n'apportent un benefice qu'aux patients ayant des blastes exprimant une P-gp fonctionnelle. Le role des autres pompes de la meme famille ( multidrug resistance associated protein [MRP] et breast cancer resistance protein [BCRP]) n'a pas fait la preuve de son importance pronostique dans les hemopathies malignes. Un autre mecanisme important est l'inhibition de l'apoptose chimio-induite, par modification de la p53 et/ou des proteines de la famille bcl2. Les modifications enzymatiques de synthese et de degradation des analogues de nucleotides sont a l'origine des resistances a la cytosine arabinoside, largement utilisee dans le traitement des leucemies aigues. L'emploi de doses dix fois superieures a celles utilisees normalement permet de depasser cette resistance.
- Published
- 2006
44. MRP3, BCRP, and P-Glycoprotein Activities are Prognostic Factors in Adult Acute Myeloid Leukemia
- Author
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Jean-Pierre Marie, Ollivier Legrand, Anne Marie Faussat, Hamid Morjani, Jean-Yves Perrot, Christophe Marzac, Driss Chaoui, Lydia Sayada, Ruoping Tang, and Zineb Benderra
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Abcg2 ,CD34 ,Antigens, CD34 ,Text mining ,Cell Line, Tumor ,Internal medicine ,medicine ,ATP Binding Cassette Transporter, Subfamily G, Member 2 ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Aged ,P-glycoprotein ,Models, Statistical ,biology ,business.industry ,Multidrug resistance-associated protein 2 ,Myeloid leukemia ,Biological activity ,Adult Acute Myeloid Leukemia ,Middle Aged ,Flow Cytometry ,Prognosis ,Drug Resistance, Multiple ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Multivariate Analysis ,Immunology ,biology.protein ,ATP-Binding Cassette Transporters ,Multidrug Resistance-Associated Proteins ,K562 Cells ,business - Abstract
Purpose: P-Glycoprotein (Pgp) is associated with poor outcome in acute myeloid leukemia (AML). We have investigated other ATP-binding cassette proteins such as BCRP, MRP1, MRP2, MRP3, and MRP5 for their potential implication in chemoresistance. Experimental Design and Results: Eighty five AML patient samples were analyzed in this study. First, MRP3 function was higher in patients which had a high level of leukocytes (P = 0.01), a M5 FAB subtype (P = 0.04), and an intermediate or poor cytogenesis (P = 0.05). BCRP activity was not correlated with clinical or biological variables, but high Pgp activity was correlated with the following variables: CD34 expression (P = 0.002), FAB subtype (P = 0.002), intermediate or poor cytogenesis (P = 0.02), and elderly patients (P = 0.03). Second, Pgp, MRP3, and BCRP activities were correlated with complete remission (P = 0.02, P = 0.04, and P = 0.04, respectively), disease-free survival (P = 0.02, P = 0.03, and P = 0.25, respectively), and overall survival (P = 0.04, P = 0.04, and P = 0.05, respectively) in multivariate analysis. The patient samples expressing one or none of these Pgp, MRP3, or BCRP functional proteins have a better prognosis than the patients expressing two or three of these functional proteins (complete remission, P = 0.02; disease-free survival, P = 0.01; overall survival, P < 0.001). Conclusions: BCRP and MRP3 may also be involved in chemoresistance in AML, especially MRP3 in patients with M5 FAB. Additional modulation of BCRP or MRP3 to Pgp modulation may be necessary in some patients in order to improve the treatment outcome.
- Published
- 2005
45. Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?
- Author
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Didier Bouscary, Sylvie Ramond, Jean-Pierre Marie, Alain Delmer, Franck Viguié, Azzedine Aboura, Nicole Casadevall, and Gérard Tachdjian
- Subjects
Cancer Research ,medicine.medical_specialty ,Pathology ,Chromosomal translocation ,Biology ,Translocation, Genetic ,Internal medicine ,medicine ,Humans ,Genes, Tumor Suppressor ,In Situ Hybridization, Fluorescence ,Gene Rearrangement ,Hematology ,Myeloid leukemia ,Hematopoietic stem cell ,Karyotype ,Middle Aged ,Hematopoietic Stem Cells ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Oncology ,Leukemia, Myeloid ,Myelodysplastic Syndromes ,Acute Disease ,Female ,Bone marrow ,Chromosome Deletion ,Chromosomes, Human, Pair 4 ,Stem cell - Abstract
We determined bone marrow karyotype at diagnosis in four female acute myeloid leukemia (AML) or myelodysplasia patients, aged between 52 and 56 years. In each case, we observed chromosome rearrangement involving the same 4q24 band. Three patients had a balanced reciprocal translocation as the sole abnormality - t(3;4)(q26;q24), t(4;5)(q24;p16) and t(4;7)(q24;q21) - and the fourth had del(4)(q23q24), +4. We used a set of 4q BAC probes for fluorescent in situ hybridization (FISH) in these four cases. We found a 4q24 submicroscopic deletion in all three translocations, with a common deletion of approximately 0.5 Mb. In three cases, we concluded that rearrangement occurred in an early hematopoietic stem cell, as it was detected, in mosaic with a normal karyotype, in a fraction of remission bone marrow cells, peripheral T and B lymphocytes, malignant lymph node T-lymphoma cells in one case and B-lymphoblastoid cell lines established in two cases. Moreover, one of 10 additional AML patients tested by FISH had a normal karyotype and deletion of one of the commonly deleted probe sequences. A tumor suppressor gene may therefore be involved, especially as two patients developed malignant lymphoma at the same time as myeloid proliferation.
- Published
- 2005
46. Lethal Pulmonary Hemorrhage Caused by a FulminantStenotrophomonas maltophiliaRespiratory Infection in an Acute Myeloid Leukemia Patient
- Author
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Antoine Rabbat, Anne Casetta, Josée Audouin, Jean-Pierre Marie, Liliane Amrouche, Audrey Rousseau, Thierry Molina, Agnès Le Tourneau, Mohib Morcos, Elena Foïs, and Bernard Rio
- Subjects
Lung Diseases ,Cancer Research ,Stenotrophomonas maltophilia ,Fulminant ,Hemorrhage ,Bronchoalveolar Lavage ,Immunocompromised Host ,Fatal Outcome ,Pneumonia, Bacterial ,Humans ,Medicine ,biology ,medicine.diagnostic_test ,business.industry ,Myeloid leukemia ,Respiratory infection ,Hematology ,Middle Aged ,medicine.disease ,biology.organism_classification ,Pneumonia ,Leukemia ,Bronchoalveolar lavage ,Oncology ,Leukemia, Myeloid ,Acute Disease ,Immunology ,Female ,Pulmonary hemorrhage ,Gram-Negative Bacterial Infections ,business ,Bronchoalveolar Lavage Fluid - Abstract
Stenotrophomonas maltophilia (Sm) pneumonia in immunocompromized hosts is an increasingly common nosocomial infection. Even though resistant to multiple antimicrobials, this gram-negative bacteria usually does not present with a fulminant course leading to a fatal hemorrhagic respiratory infection in neutropenic patients. We report here the case of a 63-year-old woman treated by intensive chemotherapy for acute myeloid leukemia (AML) who presented while severely neutropenic and thrombocytopenic a Sm pulmonary infection with hemoptysis leading to death in 48 h. The bronchoalveolar lavage (BAL) performed shortly before death was highly hemorrhagic and contained a striking amount of extra- and intra-cellular pathogens. Blood and BAL cultures grew S. maltophilia. Post-mortem examination revealed bilateral extensive intra-alveolar hemorrhage (IAH) associated with a great amount of microorganisms and severe bone marrow aplasia was observed without evidence of leukemia residual disease. Sm pneumonia usually does not evolve into such a devastating clinical picture although infections due to the bacteria are known to be associated with high morbidity and mortality. So far, the present observation is the fourth similar case reported in the literature. Even though an early diagnosis and an adequate antibiotic prescription may improve Sm infection prognosis, S. maltophilia proves difficult to eradicate due to a high resistance rate in part intrinsic but also in part acquired.
- Published
- 2004
47. Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1
- Author
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Jean-Pierre Marie, O. Legrand, Chaoui D, Anne-Marie Faussat, Ruoping Tang, Jean-Yves Perrot, and Majdak P
- Subjects
Cancer Research ,HL60 ,medicine.drug_class ,CASP8 and FADD-Like Apoptosis Regulating Protein ,Drug Evaluation, Preclinical ,Apoptosis ,Biology ,Caspase 8 ,chemistry.chemical_compound ,Cell Line, Tumor ,Tumor Cells, Cultured ,medicine ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Enzyme Inhibitors ,Valproic Acid ,Histone deacetylase inhibitor ,Cytarabine ,Intracellular Signaling Peptides and Proteins ,Myeloid leukemia ,Drug Synergism ,Hematology ,medicine.disease ,Drug Resistance, Multiple ,Leukemia ,Oncology ,chemistry ,Leukemia, Myeloid ,Cell culture ,Acute Disease ,Cancer research ,lipids (amino acids, peptides, and proteins) ,Multidrug Resistance-Associated Proteins ,Carrier Proteins ,Cell Division ,K562 cells - Abstract
The multidrug resistance (MDR) phenotype, induced by the overexpression of several ABC transporters or by antiapoptotic mechanisms, has been identified as the major cause of drug resistance in the treatment of patients with acute myeloid leukemia (AML). In this study, we have shown that valproic acid (VPA) (a histone deacetylase inhibitor) can inhibit the proliferation of both P-glycoprotein (P-gp)- and MDR-associated protein 1 (MRP1)-positive and -negative cells. VPA also induced apoptosis of P-gp-positive cells. VPA induced apoptosis in K562 cells led to decrease in Flip (FLICE/caspase-8 inhibitory protein) expression with Flip cleavage, which could not be observed in HL60 cells. In HL60/MRP cell line, which proved to be resistant to apoptosis by VPA, we observed an abnormal expression of apoptotic regulatory proteins, overexpression of Bcl-2 and absence of Bax. Also, the Bcl-2 antagonist HA14-1 rapidly restored apoptosis in this cell line. Cotreatment with cytosine arabinoside induced very strong apoptosis in both K562/DOX and HL60/DNR cell lines. VPA also induced apoptosis in AML patient cells expressing P-gp and/or MRP1. Our findings show VPA as an interesting drug that should be tested in clinical trials for overcoming the MDR phenotype in AML patients.
- Published
- 2004
48. Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B
- Author
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Chantal Doyen, Catherine Cordonnier, Simon Durrant, Ben E. De Pauw, Jean-Pierre Marie, George Samonis, Philippe Moreau, Dan Engelhard, Richard Sylvester, Vladimir Krcmery, Harry F. L. Guiot, Patricia Ribaud, Marc Boogaerts, Raoul Herbrecht, and Fritz Offner
- Subjects
Adult ,Male ,Nystatin ,medicine.medical_specialty ,Antifungal Agents ,Neutropenia ,Adolescent ,Survival ,Salvage therapy ,Clinical Therapeutics ,Aspergillosis ,Gastroenterology ,Drug Resistance, Fungal ,Interventional oncology [UMCN 1.5] ,Amphotericin B ,Cause of Death ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Child ,Adverse effect ,Mycosis ,Aged ,Salvage Therapy ,Pharmacology ,business.industry ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,Infectious Diseases ,Liposomes ,Female ,Chills ,medicine.symptom ,business ,Follow-Up Studies ,medicine.drug - Abstract
We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.
- Published
- 2004
49. Comparison of flow cytometry and enzyme cytochemistry for the detection of myeloperoxydase in acute myeloid leukaemia: interests of a new positivity threshold
- Author
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Régis Peffault de Latour, Jean-Pierre Marie, Claude Blanc, Nicole Casadevall, Ollivier Legrand, Delphine Moreau, Driss Chaoui, and Jean-Yves Perrot
- Subjects
chemistry.chemical_classification ,medicine.diagnostic_test ,Adult patients ,Hematology ,Biology ,medicine.disease ,Flow cytometry ,Leukemia ,Enzyme ,chemistry ,Predictive value of tests ,Concomitant ,Immunology ,medicine ,Cytochemistry ,Myeloid leukaemia - Abstract
Following the recommendations of the European Group for the Immunological Characterization of Leukaemias (EGIL) in 1995, few reports have been published comparing enzyme cytochemistry (EC) and flow cytometry (FC) for the detection of myeloperoxydase (MPO) in acute myeloid leukaemia (AML). The EGIL guidelines defined MPO positivity in FC, by the presence of this enzyme in 10% or more of the blast cells. We studied 136 adult patients with the systematic use of both EC and FC, using a 3% threshold for positivity for EC, and 10% and 3% consecutively for FC. FC was less sensitive than EC using the currently recommended threshold of 10%, but a 3% cut-off showed more sensitivity and was superior to EC. The joint use of both techniques identified 14 discordant patients (positive in FC/negative in EC or vice versa), all of whom displayed at least one poor-prognosis biological factor, which correlated with a mediocre clinical result. In conclusion, we recommend that the cut-off for a positive MPO value should be lowered to 3%, and suggest that the concomitant use of FC and EC is a fast clinically relevant prognostic tool.
- Published
- 2003
50. Impact thérapeutique des bactériémies à streptocoques et à entérocoques chez des malades d'hématologie
- Author
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L. Schlegel, Jean-Pierre Marie, E. Ombandza-Moussa, Anne Vekhoff, R. Gerbal, and A. Bouvet
- Subjects
Cefotaxime ,biology ,business.industry ,General Medicine ,Amoxicillin ,biology.organism_classification ,Enterococcus faecalis ,Microbiology ,Penicillin ,Enterococcus ,medicine ,Vancomycin ,business ,Piperacillin ,medicine.drug ,Antibacterial agent - Abstract
From January 1999 to May 2000 (17 months), 21 strains of streptococci and four strains of enterococci have been isolated from 74 blood cultures in 25 infectious episodes in hematologic patients. They concerned 21 patients, of 21 to 77 years old. These patients suffered from acute leukaemia (14 cases), chronic lymphoid leukaemia (two cases), non-Hodgkin's lymphoma (two cases) or myeloma (three cases). Seventeen patients displayed a single streptococcal or enterococcal episode, two had two episodes in the course of a single stay in the hospital, two others in the course of two different stays. During 16 episodes (64%), the bacteremia occurred within 15 days after the onset of neutropenia consecutive to antimitotic chemotherapy, and in nine episodes (36%) it has occurred after a period exceeding 15 days. In six cases the patients had already received antibiotics with a large antibacterial activity (beta-lactam, fluoroquinolone and/or glycopeptide +/- aminoside) and in four cases a single antibiotic (synergistine or cotrimoxazole). Most streptococci (20/21) were oral streptococci (ten Streptococcus mitis, five S. oralis, two S. sanguis, three S. pneumoniae). A single strain of beta-hemolytic streptococci has been identified as S. dysgalactiae subsp. equisimilis. The enterococci were one strain of Enterococcus faecalis and three E. faecium. Ten streptococci were susceptible to 0.25 mg/L of penicillin G, ten were less susceptible (0.5 < or = MIC < 32 mg/L), and a strain was resistant (MIC = 32 mg/L). Eighteen strains were susceptible to amoxicillin and cefotaxime. For three strains, the MICs of amoxicillin and cefotaxime (8-16 mg/L and 8-32 mg/L, respectively) were higher. Levels of resistance of the enterococci to the beta-lactam (penicillin, amoxicillin, and piperacillin) were variable. All species were susceptible to glycopeptides. Three patients were transferred in intensive care unit for respiratory distress or shock syndrome. Their evolution has remained severe under antibiotherapy comprising beta-lactam or vancomycin associated with an aminoside. This results demonstrate the interest of species identification to adapt the antibiotic treatment and confirms the frequency of oral streptococci in severe bacteremia in neutropenic patients.
- Published
- 2002
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