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Rouen, France

Hebraud B.,French Institute of Health and Medical Research | Caillot D.,Service dhematologie | Corre J.,French Institute of Health and Medical Research | Marit G.,Bordeaux University Hospital Center | And 26 more authors.
Clinical Cancer Research | Year: 2013

Purpose: Although the translocation t(4;14) is supposed to be a primary event in multiple myeloma, we have been surprised to observe that in large relapse series of patients, the t(4;14) can be observed only in subpopulations of plasma cells, in contrast to what is seen at diagnosis. This observation raised the question of possible subclones harboring the translocation that would be observable only at the time of relapse. Experimental Design: To address this issue, we analyzed by FISH a cohort of 306 patients for whom we had at least two samples obtained at different disease phases. Results: Weobserved a "gain" of the t(4;14) in 14 patients, and conversely, a "loss" of the translocation in 11 patients. Two hypotheses were raised: either an acquisition of the translocation during evolution or the existence of small t(4;14)-positive subclones at the time of diagnosis. To address this question, we had the opportunity to analyze two patients at the time of diagnosis by RT-PCR (reverse transcription-polymerase chain reaction) to look for the chimeric Eμ-MMSET transcript, and one patient positive at diagnosis, but negative at relapse. The samples were positive, supporting the second hypothesis. Furthermore, the IGH sequences of two patients who "lose" the t(4;14) were identical at diagnosis and relapse, confirming the existence of a common ancestral clone. Conclusion: Thus, the conclusion of this study is that the t(4;14) is not a primary event in multiple myeloma and that it can be present in silent subclones at diagnosis, but also at relapse. ©2013 AACR. Source

Baron M.,Center Becquerel | Fondrinier E.,Center Hospitalier Henri Mondor dAurillac | Laberge S.,Center Becquerel
Bulletin du Cancer | Year: 2012

From the analysis of our series and a review of the literature, we have done a summary of the clinicopathologic patterns and treatment of squamous cell carcinoma of the breast. It usually presents as a large palpable mass in a woman over 50 years old. There are no specific iconographic features, but a relative frequency of presentation as abscess or cyst. The overall and disease-free survivals are worse than other histological types of breast cancer. These neoplasms have a basallike and triple negative profile and they respond poorly to standard treatment of breast carcinomas. They are usually treated by radical surgery. Optimal chemotherapy regimens is not yet determined and platin based chemotherapy could offer an effective alternative as the developpement of specific targeted therapies (anti Her1) could do. ©John Libbey Eurotext. Source

Chretien M.-L.,University Paul Sabatier | Chretien M.-L.,University Hospital | Hebraud B.,University Paul Sabatier | Cances-Lauwers V.,Toulouse University Hospital Center | And 23 more authors.
Haematologica | Year: 2014

Age is a strong prognostic factor in multiple myeloma. The overall survival is shorter in patients older than 66 years, and even shorter in those older than 75 years. Whether age is also a prognostic parameter in patients younger than 66 years treated homogeneously with intensive approaches is unknown. To address this issue, we retrospectively analyzed a series of 2316 patients treated homogeneously with 3-4 cycles of induction chemotherapy followed by a high-dose melphalan course, without any consolidation or maintenance. We show that patients older than 60 years have a statistically significant shorter overall survival. The analysis of prognostic parameters did not show a higher incidence of high-risk cytogenetics, but a higher incidence of International Staging System (ISS) stages 2 and 3, mainly due to higher β2-microglobulin levels. This study is the first to demonstrate the impact of age in the outcome of 'young' patients with multiple myeloma, and suggests that this parameter should be included in the stratification factors for future prospective clinical trials. © 2014 Ferrata Storti Foundation. Source

Moreau P.,University of Nantes | Avet-Loiseau H.,University of Nantes | Facon T.,University Hospital | Attal M.,University Hospital | And 27 more authors.
Blood | Year: 2011

The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-dexamethasone (VD) as induction before high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone (vtD) in patients with multiple myeloma. Overall, a total of 199 patients were centrally randomly assigned to receive VD or vtD. After 4 cycles, the complete response (CR) rate was the same in both groups (13% in the vtD arm, 12% in the VD arm, P = .74). However, the CR plus very good partial response (VGPR) rate was significantly higher in the vtD arm (49% vs 36%, P = .05). After ASCT, the CR plus VGPR rate was significantly higher in the vtD arm (74% vs 58%, P = .02). The reduced doses of bortezomib and thalidomide translated into a reduced incidence of peripheral neuropathy (PN): grade ≥ 2 PN were reported in 34% in the VD arm versus 14% in the vtD arm (P = .001). vtD, including reduced doses of bortezomib and thalidomide, yields higher VGPR rates compared with VD and can be considered a new effective triplet combination before HDT/ASCT. This study was registered with www.clinicaltrials.gov as #NCT00910897 and EudraCT as #2007-005204-40. © 2011 by The American Society of Hematology. Source

Chantepie S.P.,Institut Universitaire de France | Mear J.-B.,Institut Universitaire de France | Guittet L.,French Institute of Health and Medical Research | Guittet L.,Caen University Hospital Center | And 6 more authors.
Trials | Year: 2015

Background: Packed red blood cell (PRBC) transfusion is required in hematology patients treated with chemotherapy for acute leukemia, autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT). In certain situations like septic shock, hip surgery, coronary disease or gastrointestinal hemorrhage, a restrictive transfusion strategy is associated with a reduction of infection and death. A transfusion strategy using a single PRBC unit has been retrospectively investigated and showed a safe reduction of PRBC consumption and costs. We therefore designed a study to prospectively demonstrate that the transfusion of a single PRBC unit is safe and not inferior to standard care. Methods: The 1versus2 trial is a randomized trial which will determine if a single-unit transfusion policy is not inferior to a double-unit transfusion policy. The primary endpoint is the incidence of severe complication (grade≥3) defined as stroke, transient ischemic attack, acute coronary syndrome, heart failure, elevated troponin level, intensive care unit transfer, death, new pulmonary infiltrates, and transfusion-related infections during hospital stays. The secondary endpoint is the number of PRBC units transfused per patient per hospital stay. Two hundred and thirty patients will be randomized to receive a single unit or double unit every time the hemoglobin level is less than 8 g/dL. All patients admitted for induction remission chemotherapy, auto-HSCT or allo-HSCT in hematology intensive care units will be eligible for inclusion. Sample size calculation has determined that a patient population of 230 will be required to prove that the 1-unit PRBC strategy is non-inferior to the 2-unit PRBC strategy. Hemoglobin threshold for transfusion is below 8 g/dL. Estimated percentage of complication-free hospital stays is 93 %. In a non-inferiority hypothesis, the number of patients to include is 230 with a power of 90 % and an alpha risk of 5 %. Trial Registration: 14-128; Clinicaltrials.gov NCT02461264(registered on 3 June 2015) © 2015 Chantepie et al. Source

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