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Romain Vazquez, Mikael Roussel, Bouchra Badaoui, Nicolas Freynet, Sihem Tarfi, Eric Solary, Dorothée Selimoglu-Buet, Orianne Wagner-Ballon
BACKGROUND: Accumulation of classical monocytes CD14++ CD16- (also called MO1) ≥ 94% can accurately distinguish chronic myelomonocytic leukemia (CMML) from reactive monocytosis. The HematoFlow™ solution, able to quantify CD16 negative monocytes, could be a useful tool to manage monocytosis which remains a common issue in routine laboratories. METHODS: Classical monocytes were quantified from 153 whole blood samples collected on EDTA using both flow cytometry methods, either MO1 percentage determination by the multiparameter assay previously published and regarded here as the reference method, or CD16 negative monocyte percentage determination by the means of HematoFlow™...
November 6, 2017: Cytometry. Part B, Clinical Cytometry
Lionel Ades, Thomas Prebet, Aspasia Stamatoullas, Christian Recher, Romain Guieze, Emmanuel Raffoux, Krimo Bouabdallah, Mathilde Hunault, Eric Wattel, Laure Stalnikiewicz, Andrea Toma, Hervé Dombret, Norbert Vey, Marie Sebert, Claude Gardin, Cendrine Chaffaut, Sylvie Chevret, Pierre Fenaux
Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within a complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with intensive chemotherapy in a phase II study. Treatment consisted of daunorubicin (45 mg/m2 /day, days 1-3 in cohort 1, escalated to 60 mg/m2 /day, days 1-3 in cohorts 2 and 3) combined with cytosine arabinoside (200 mg/m2 /day, days 1-7) and lenalidomide (10 mg/day, days 1-21 in cohorts 1 and 2, escalated to 25 mg/day, days 1-21 in cohort 3)...
April 2017: Haematologica
Mrinal M Patnaik, Ayalew Tefferi
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (>3 months) peripheral blood monocytosis (>1 × 10(9) /L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼20-30% of patients, while >90% have gene mutations. Mutations involving TET2 (∼60%), SRSF2 (∼50%), ASXL1 (∼40%), and RAS (∼30%) are frequent; with only ASXL1 mutations negatively impacting overall survival...
June 2016: American Journal of Hematology
Anna Raimbault, Cecile Pierre-Eugene, Alexandra Rouquette, Celine Deudon, Lise Willems, Nicolas Chapuis, Stephanie Mathis, Claudia Kunz, Harald Fricke, Olivier Kosmider, Valerie Bardet, Michaela Fontenay
CD95, a member of the death receptor family initiates a caspase-dependent apoptosis, when activated by its ligand CD95L, thought to negatively regulate erythrocyte production in the bone marrow. We have previously shown that CD95 is overexpressed in two thirds of patients with a lower risk myelodysplastic syndrome (MDS) and that resistance to erythropoiesis-stimulating agents (ESA) is linked to poor residual erythropoiesis. In the present study, we show that CD95 overexpression and previous transfusion are independent predictive factors of ESA resistance...
March 22, 2016: Oncotarget
M M Patnaik, A Tefferi
Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder associated with peripheral blood monocytosis and an inherent tendency to transform to acute myeloid leukemia. CMML has overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Clonal cytogenetic changes are seen in ~30%, whereas gene mutations are seen in >90% of patients. Common cytogenetic abnormalities include; trisomy 8, -Y, -7/del(7q), trisomy 21 and del(20q), with the Mayo-French risk stratification effectively risk stratifying patients based on cytogenetic abnormalities...
February 5, 2016: Blood Cancer Journal
Mrinal M Patnaik, Ayalew Tefferi
Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder with features that overlap those of myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). Chronic myelomonocytic leukemia often results in peripheral blood monocytosis and has an inherent tendency to transform to acute myeloid leukemia. Clonal cytogenetic changes are seen in approximately 30% of patients, and molecular abnormalities are seen in more than 90%. Gene mutations involving TET2 (∼60%), SRSF2 (∼50%), ASXL1 (∼40%), and RAS (∼30%) are frequent, with nonsense and frameshift ASXL1 mutations being the only mutations identified thus far to have an independent negative prognostic effect on overall survival...
February 2016: Mayo Clinic Proceedings
Kristen B McCullough, Mrinal M Patnaik
Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder, characterized by peripheral blood monocytosis and overlapping features between myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). Clonal cytogenetic changes are seen in up to 30 % patients, while approximately 90 % have detectable molecular abnormalities. Most patients are diagnosed in the seventh decade of life. Gene mutations in ten-eleven translocation (TET) oncogene family member 2 (TET2) (60 %), SRSF2 (50 %), ASXL1 (40 %), and RAS (20-30 %) are frequent, with only frame shift and nonsense ASXL1 mutations negatively impacting overall survival...
September 2015: Current Hematologic Malignancy Reports
Charles Herbaux, Nicolas Duployez, Catherine Badens, Nicolas Poret, Claude Gardin, Mathieu Decamp, Virginie Eclache, Sylvie Daliphard, Anne Murati, Pascale Cony-Makhoul, Stéphane Cheze, Blandine Beve, Caroline Lacoste, Thomas Prebet, Mathilde Hunault-Berger, Frédéric Maloisel, Aline Renneville, Martin Figeac, Aspasia Stamatoullas-Bastard, Christian Bastard, Pierre Fenaux, Claude Preudhomme, Christian Rose
Acquired α-thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assessed the incidence of ATMDS in microcytic MDS. In this study, we focused on patients with MDS and unexplained microcytosis, which was defined as absence of iron deficiency, inflammatory disease, or history of inherited hemoglobinopathy...
August 2015: American Journal of Hematology
Valérie Bardet, Orianne Wagner-Ballon, Julien Guy, Céline Morvan, Camille Debord, Franck Trimoreau, Emmanuel Benayoun, Nicolas Chapuis, Nicolas Freynet, Cédric Rossi, Stéphanie Mathis, Marie-Pierre Gourin, Andréa Toma, Marie C Béné, Jean Feuillard, Estelle Guérin
Although numerous recent publications have demonstrated interest in multiparameter flow cytometry in the investigation of myelodysplastic disorders, it is perceived by many laboratory hematologists as difficult and expensive, requiring a high level of expertise. We report a multicentric open real-life study aimed at evaluating the added value of the technically simple flow cytometry score described by the Ogata group for the diagnosis of myelodysplastic syndromes. A total of 652 patients were recruited prospectively in four different centers: 346 myelodysplastic syndromes, 53 myelodysplastic/myeloproliferative neoplasms, and 253 controls...
April 2015: Haematologica
Sylvain Thepot, Simone Boehrer, Valérie Seegers, Thomas Prebet, Odile Beyne-Rauzy, Eric Wattel, Jacques Delaunay, Emmanuel Raffoux, Mathilde Hunault, Eric Jourdan, Fatiha Chermat, Marie Sebert, Guido Kroemer, Pierre Fenaux, Lionel Adès
Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100mg/day (n=5) or 150mg/day (n=25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated...
December 2014: Leukemia Research
Arsène Mekinian, Thorsten Braun, Olivier Decaux, Géraldine Falgarone, Eric Toussirot, Loic Raffray, Mohamed Omouri, Bruno Gombert, Benoit De Wazieres, Anne-Laure Buchdaul, Jean-Marc Ziza, David Launay, Guillaume Denis, Serge Madaule, Christian Rose, Eric Grignano, Pierre Fenaux, Olivier Fain
We describe the characteristics and outcome of inflammatory arthritis in patients with myelodysplastic syndrome (MDS) in a French multicenter retrospective study. Twenty-two patients with MDS (median age, 77.5 yr [interquartile range, 69-81]; 10 women) were included. Inflammatory arthritis presented as polyarthritis in 17 cases (77%) and with symmetric involvement in 15 cases (68%). At diagnosis, the median disease activity score 28 based on C-reactive protein (DAS28-CRP) was 4.5 [2-6.5]. Two patients had anti-citrullinated protein antibodies (ACPAs), and 1 had radiologic erosions...
January 2014: Medicine (Baltimore)
Sylvain Thépot, Raphael Itzykson, Valerie Seegers, Christian Recher, Emmanuel Raffoux, Bruno Quesnel, Jacques Delaunay, Thomas Cluzeau, Anne Marfaing Koka, Aspasia Stamatoullas, Marie-Pierre Chaury, Caroline Dartigeas, Stéphane Cheze, Anne Banos, Pierre Morel, Isabelle Plantier, Anne-Laure Taksin, Jean Pierre Marolleau, Cecile Pautas, Xavier Thomas, Francoise Isnard, Blandine Beve, Yasmine Chait, Agnes Guerci, Norbert Vey, Francois Dreyfus, Lionel Ades, Norbert Ifrah, Herve Dombret, Pierre Fenaux, Claude Gardin
Limited data are available on azacitidine (AZA) treatment and its prognostic factors in acute myeloid leukemia (AML). One hundred and forty-nine previously untreated AML patients considered ineligible for intensive chemotherapy received AZA in a compassionate patient-named program. AML diagnosis was de novo, post-myelodysplastic syndromes (MDS), post-MPN, and therapy-related AML in 51, 55, 13, and 30 patients, respectively. Median age was 74 years, median white blood cell count (WBC) was 3.2 × 10⁹ /L and 58% of the patients had ≥ 30% marrow blasts...
April 2014: American Journal of Hematology
Benoit de Renzis, Veronique Mansat-De Mas, Eric Wattel, Odile Beyne-Rauzy, Laurent Knoops, Aurélie Cabrespine, Zahia Azgui, Lionel Ades, Jean-Jacques Kiladjian, Pierre Fenaux
While in RARS-T, JAK2V617F mutation is common and associated with good prognosis, the clinical and prognostic impact of this mutation in other MDS is unknown. We collected data from 132 non-RARS-T MDS with known JAK2V617F mutation status. JAK2V617F mutation was significantly correlated with lower progression to AML (p<.0011) and better overall survival (OS, p=.011). OS difference persisted after matching on age, sex, IPSS and % marrow blast (p=.031). Thus, in MDS other than RARS-T, JAK2V617F mutation may be associated with favorable outcome...
2013: Leukemia Research Reports
Cecile Bally, Sylvain Thépot, Bruno Quesnel, Norbert Vey, Francois Dreyfus, Jehane Fadlallah, Pascal Turlure, Stephane de Botton, Caroline Dartigeas, Benoit de Renzis, Raphael Itzykson, Pierre Fenaux, Lionel Adès
The effect of azacitidine (AZA) in therapy related MDS and AML (t-MDS/AML) is not well established. 54 patients (42 t-MDS and 12 t-AML), 71% of whom had complex karyotype, received AZA for at least one cycle (median 4 cycles). The overall response rate (ORR) was 39% in the whole cohort and 62% in patients who received ≥4 cycles. One, 2 and 3 year OS was 36%, 14% and 8% respectively. Female gender (p=0.01) and ECOG 0-1 (p=0.04) were associated with significantly better OS, while karyotype and marrow blast percentage had no significant impact...
June 2013: Leukemia Research
Gandhi Damaj, Alain Duhamel, Marie Robin, Yves Beguin, Mauricette Michallet, Mohamad Mohty, Stephane Vigouroux, Pierre Bories, Alice Garnier, Jean El Cheikh, Claude-Eric Bulabois, Anne Huynh, Jacques-Olivier Bay, Faeyzeh Legrand, Eric Deconinck, Nathalie Fegueux, Laurence Clement, Charles Dauriac, Natacha Maillard, Jérôme Cornillon, Lionel Ades, Gaelle Guillerm, Aline Schmidt-Tanguy, Zora Marjanovic, Sophie Park, Marie-Thérèse Rubio, Jean-Pierre Marolleau, Federico Garnier, Ierre Fenaux, Ibrahim Yakoub-Agha
PURPOSE: To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17)...
December 20, 2012: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Uwe Platzbecker, Johannes Schetelig, Jürgen Finke, Rudolf Trenschel, Bart L Scott, Guido Kobbe, Kerstin Schaefer-Eckart, Martin Bornhäuser, Raphael Itzykson, Ulrich Germing, Dietrich Beelen, Gerhard Ehninger, Pierre Fenaux, H Joachim Deeg, Lionel Adès
Standard first-line therapy for older patients with high-risk myelodysplastic syndrome (MDS) includes hypomethylating agents, such as azacitidine (AZA). However, the only approach with curative potential remains allogeneic hematopoietic cell transplantation (HCT). To date, no direct comparison of both strategies has been reported. The outcomes of 2 well-balanced cohorts of patients with high-risk MDS defined by age (60-70 years), performance status (Eastern Cooperative Oncology Group score ≤2), and donor availability (yes/no) were compared, including 103 patients undergoing HCT and 75 patients without this option who received AZA...
September 2012: Biology of Blood and Marrow Transplantation
Shanti Natarajan-Amé, Sophie Park, Lionel Ades, Norbert Vey, Agnès Guerci-Bresler, Jean-Yves Cahn, Gabriel Etienne, Dominique Bordessoule, Christophe Ravoet, Laurence Legros, Stephane Cheze, Aspasia Stamatoullas, Elisabeth Berger, Aline Schmidt, Aude Charbonnier, Marie-Pierre Chaury, Thorsten Braun, Pierre Fenaux, Francois Dreyfus
Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m(2) , days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m(2) , then 20 mg/m(2) from days 1-14), every 28 d for four cycles...
July 2012: British Journal of Haematology
Frederik Damm, Olivier Kosmider, Véronique Gelsi-Boyer, Aline Renneville, Nadine Carbuccia, Claire Hidalgo-Curtis, Véronique Della Valle, Lucile Couronné, Laurianne Scourzic, Virginie Chesnais, Agnes Guerci-Bresler, Bohrane Slama, Odile Beyne-Rauzy, Aline Schmidt-Tanguy, Aspasia Stamatoullas-Bastard, François Dreyfus, Thomas Prébet, Stéphane de Botton, Norbert Vey, Michael A Morgan, Nicholas C P Cross, Claude Preudhomme, Daniel Birnbaum, Olivier A Bernard, Michaela Fontenay
A cohort of MDS patients was examined for mutations affecting 4 splice genes (SF3B1, SRSF2, ZRSR2, and U2AF35) and evaluated in the context of clinical and molecular markers. Splice gene mutations were detected in 95 of 221 patients. These mutations were mutually exclusive and less likely to occur in patients with complex cytogenetics or TP53 mutations. SF3B1(mut) patients presented with lower hemoglobin levels, increased WBC and platelet counts, and were more likely to have DNMT3A mutations. SRSF2(mut) patients clustered in RAEB-1 and RAEB-2 subtypes and exhibited pronounced thrombocytopenias...
April 5, 2012: Blood
David Sibon, Giovanna Cannas, Fiorenza Baracco, Thomas Prebet, Norbert Vey, Anne Banos, Caroline Besson, Selim Corm, Michel Blanc, Bohrane Slama, Hervé Perrier, Pierre Fenaux, Eric Wattel
Lenalidomide (LEN) has been shown to yield red blood cell (RBC) transfusion independence in about 25% of lower risk myelodysplastic syndromes (MDS) without del(5q), but its efficacy in patients clearly refractory to erythropoiesis-stimulating agents (ESA) is not known. We report on 31 consecutive lower-risk non-del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion-dependent (RBC-TD) patients, who became transfusion-independent (RBC-TI)...
March 2012: British Journal of Haematology
R Itzykson, S Thépot, O Beyne-Rauzy, S Ame, F Isnard, F Dreyfus, C Salanoubat, A L Taksin, Y Chelgoum, C Berthon, J V Malfuson, L Legros, N Vey, P Turlure, C Gardin, S Boehrer, L Ades, P Fenaux
We studied a retrospective cohort of 282 higher-risk MDS treated with azacitidine, including 32 patients who concomitantly received an ESA for a median of 5.8 months after azacitidine onset. Forty-four percent of ESA and 29% of no-ESA patients reached HI-E (p=0.07); 48% and 20% achieved transfusion independence (p=0.01). Median OS was 19.6 months in the ESA and 11.9 months in the no-ESA groups (p=0.04). Addition of an ESA significantly improved OS (p=0.03) independently of azacitidine schedule and duration, and of our proposed azacitidine risk score (Blood 2011;117:403-11)...
April 2012: Leukemia Research
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