Bruno Cazin

Publications (11)51.02 Total impact

• Article: Impact of dose intensity on the outcomes of fludarabine, cyclophosphamide, and rituximab regimen given in the first-line therapy of chronic lymphocytic leukemia.

  Emmanuelle Bouvet, Cécile Borel, Lucie Obéric, Gisèle Compaci, Bruno Cazin, Anne-Sophie Michallet, Guy Laurent, Loic Ysebaert
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  ABSTRACT: Background. fludarabine-cyclophosphamide-rituximab is the most efficient first-line treatment for chronic lymphocytic leukemia patients. Many dose adjustments of the original MD Anderson Cancer Center regimen have been proposed. However, whether fludarabine-cyclophosphamide-rituximab relative dose intensity may impact outcome has not been investigated before. Design and Methods. we retrospectively assessed relative dose intensity in 106 community-based patients, included in our regional healthcare network from 2004-11, all receiving fludarabine-cyclophosphamide-rituximab first-line outside a clinical trial. Results. Dose reductions were noticed in 51.4% of patients, mainly due to physician's individual decision not based on recommendation (52.7%) while documented toxicity or dose reduction because of impaired renal function played lesser roles. Progression-free survival was significantly reduced in patients who had a reduction of dose intensity greater than 20% in fludarabine-cyclophosphamide and/or rituximab. On multivariate analysis, dose of rituximab has significant impact on was significantly linked to prolonged minimal residual disease and progression-free survival. Though prophylactic gGranulocyte-cColony sStimulating fFactor significantly reduced the rate of grade 3-4 neutropenia and febrile neutropenia, it but had no impact on relative dose intensity and outcome. Conclusions. this study shows that, in routine clinical practice, the adherence rate to the original MD Anderson Cancer Center fludarabine-cyclophosphamide-rituximab schedule is low, mostly due to individual physician's decision based on anticipated toxicity. This study shows that reduction of fludarabine-cyclophosphamide and, more importantly, of rituximab doses seriously interfere with progression-free survival.
  Haematologica 10/2012; · 6.42 Impact Factor
• Article: Rituximab-cyclophosphamide-dexamethasone combination in management of autoimmune cytopenias associated with chronic lymphocytic leukemia.

  Anne-Sophie Michallet, Julien Rossignol, Bruno Cazin, Loic Ysebaert
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  ABSTRACT: We report our experience on rituximab-cyclophosphamide-dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders in 48 patients with chronic lymphocytic leukemia (CLL). The diagnosis of autoimmune disease (AID) was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenic purpura (AITP) in nine (18.8%), Evans syndrome in eight (16.7%), and pure red cell anemia (PRCA) in five patients (10.5%). CLL was considered progressive in 40% of subjects upon AID diagnosis. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). The median duration of autoimmunity was 24 months, but the duration of response of autoimmunity (DR-AI) was higher for patients presenting with: (1) AID early during the CLL course (<3 years), or (2) both and pure red cell aplasia (PRCA) in five patients (10.5%) and AIHA.
  Leukemia & lymphoma 07/2011; 52(7):1401-3. · 2.40 Impact Factor
• Article: Stem cell transplantation after alemtuzumab in T-cell prolymphocytic leukaemia results in longer survival than after alemtuzumab alone: a multicentre retrospective study.

  Biju Krishnan, Monica Else, Geir E Tjonnfjord, Bruno Cazin, Dennis Carney, John Carter, Nicolas Ketterer, Daniel Catovsky, Mark Ethell, Estella Matutes, Claire E Dearden
  British Journal of Haematology 03/2010; 149(6):907-10. · 4.94 Impact Factor
• Source

  Available from: Beatrice Mahe

  Article: IGHV gene mutational status and LPL/ADAM29 gene expression as clinical outcome predictors in CLL patients in remission following treatment with oral fludarabine plus cyclophosphamide.

  Karim Maloum, Catherine Settegrana, Elise Chapiro, Bruno Cazin, Stéphane Leprêtre, Alain Delmer, Michel Leporrier, Brigitte Dreyfus, Olivier Tournilhac, Beatrice Mahe, Florence Nguyen-Khac, Claude Lesty, Frederic Davi, Hélène Merle-Béral
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  ABSTRACT: Several prognostic factors can predict the rapid progression in chronic lymphocytic leukaemia (CLL), including IGHV mutational status, cytogenetic abnormalities and, more recently, LPL/ADAM29 expression. In contrast, few studies have been devoted to the influence of these factors on clinical outcome in responding patients after therapy. We here propose to analyse the impact of IGHV gene status, LPL and ADAM29 gene expression on disease-free survival (DFS) and overall survival (OS) in 41 stage B or C CLL patients in remission after oral fludarabine plus cyclophosphamide. The median follow-up was of 64 (16-74) months. Sequencing of IGHV showed mutated (M) VH genes in 16 of 41 cases and unmutated (UM) in 25 cases. Analysis of LPL and ADAM29 expression in 35 of 41 cases showed overexpression of ADAM29 in 17 cases (14 M and three UM) and LPL in 18 cases (all UM). Patients expressing UM IGHV and LPL had shorter DFS and OS when compared to patients expressing M IGHV and/or ADAM29. Furthermore, blood minimal residual disease (MRD) evaluation using four-colour flow cytometry was performed in 33 out the 41 patients. We showed that patients who achieved phenotypic remission displayed longer DFS than those with MRD(+). Our results support the use of LPL and ADAM29 gene expression associated to IGHV mutational status for predicting the clinical outcome of patients treated by oral fludarabine + cyclophosphamide and could be considered for treatment strategies.
  Annals of Hematology 05/2009; 88(12):1215-21. · 2.62 Impact Factor
• Article: Cost effectiveness of oral fludarabine in chronic lymphocytic leukaemia: the French case

  Benoît Dervaux, Xavier Lenne, Didier Theis, Marie-José D'Alche-Gautier, Pierre Rufat, Bruno Cazin, Karim Maloum, Michel Leporrier
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  ABSTRACT: The objective was to assess the medicoeconomic impact of initial and subsequent treatments based on oral fludarabine, intravenous chemotherapy (mini-CHOP) and chlorambucil in chronic lymphocytic leukaemia. A Markov model has been defined to encompass the 18 strategies over a 3-year period after starting the first treatment. Costs of treatments, side effects and follow-up have been calculated by crossing data from published prospective trials, specific hospital databases and French resource-based relative value scales. When treatments were based on mini-CHOP, different possibilities offered for hospital care were taken into account. Probalistic sensitivity analysis was performed. Whatever the modality of hospital care for mini-CHOP, the strategies based on oral fludarabine as first-line treatment are not only more effective but are also cost effective and dominate other types of scenarios. Fludarabine given orally should be preferred to mini-CHOP or chlorambucil as a first-line treatment for patients with chronic lymphocytic leukaemia.
  10/2008; 10(4):339-354.
• Article: High efficacy with five days schedule of oral fludarabine phosphate and cyclophosphamide in patients with previously untreated chronic lymphocytic leukaemia.

  Bruno Cazin, Marine Divine, Stéphane Leprêtre, Philippe Travade, Olivier Tournilhac, Alain Delmer, Jérôme Jaubert, Pierre Feugier, Brigitte Dreyfus, Béatrice Mahé, Bernard Grosbois, Frédéric Maloisel, Houchingue Eghbali, Charles Dumontet, Jacques Bénichou, Odile Guibon, Xavier Leleu, Michel Leporrier, Karim Maloum
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  ABSTRACT: A multicentre single-arm study testing the efficacy and toxicity of the oral combination of fludarabine and cyclophosphamide (FC) over 5 d in 75 patients with untreated B cell-chronic lymphocytic leukaemia. Oral FC demonstrated high efficacy with overall (OR) and complete response (CR) rates of 80% and 53%, respectively. Out of the 30 CR patients studied for Minimal Residual Disease (MRD) using 4-colour flow-cytometry and the 22 using Clonospecific polymerase chain reaction, 22 (66%) and 16 (68%), respectively, were MRD negative. Median survival and median treatment-free interval had not been reached at 7 years of follow-up. Median progression-free survival (PFS) was 5 years. Toxicity was acceptable, with 52% and 16% of National Cancer Institute grade 3/4 neutropenia and infections, respectively. Gastrointestinal toxicity was mild. Oral FC demonstrated a high efficacy and an acceptable safety profile and may be considered as the standard first line treatment in chronic lymphocytic leukaemia.
  British Journal of Haematology 09/2008; 143(1):54-9. · 4.94 Impact Factor
• Article: Autologous activated macrophages (MAK) coated ex vivo with humanized anti-CD20 monoclonal antibodies can eradicate minimal residual disease in chronic lymphocytic leukaemia in clinical response.

  Laurent Sutton, Driss Chaoui, Bruno Cazin, Nabih Azar, Mohamed Chokri, Jean-Loup Romet-Lemonne, Karim Maloum
  British Journal of Haematology 08/2008; 142(6):996-8. · 4.94 Impact Factor
• Article: Chronic lymphocytic leukaemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for improved engagement of FcgammaRIIIA/CD16.

  Christophe de Romeuf, Charles-Antoine Dutertre, Magali Le Garff-Tavernier, Nathalie Fournier, Christine Gaucher, Arnaud Glacet, Sylvie Jorieux, Nicolas Bihoreau, Christian K Behrens, Roland Béliard, Vincent Vieillard, Bruno Cazin, Dominique Bourel, Jean-François Prost, Jean-Luc Teillaud, Hélène Merle-Béral
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  ABSTRACT: Patients with chronic lymphocytic leukaemia (CLL) treated with a combination of fludarabine, cyclophosphamide and rituximab show a high response rate. However, only a poor response is observed following rituximab monotherapy. The use of chemo-immunotherapy is often associated with haematological and infectious complications. Thus, an antibody with an enhanced ability to kill CLL cells could lead to better clinical responses to antibody monotherapy and the possibility of lowering drug doses during chemo-immunotherapy. We generated a chimeric anti-CD20 monoclonal antibody (mAb), EMAB-6, which has a low fucose content. Apoptosis and complement activities for EMAB-6 were similar to those seen for rituximab. By contrast, EMAB-6 mAb showed improved Fcgamma receptor IIIA (FcgammaRIIIA)/CD16 binding and FcgammaRIIIA-dependent effector functions. It induced a higher in vitro antibody-dependent cellular cytotoxicity against CLL cells and a higher FcgammaRIIIA-mediated interleukin-2 production by FcgammaRIIIA(+) Jurkat cells in the presence of CLL cells at both low and maximally saturating concentrations. Comparative studies between CLL and lymphoma cells coated with EMAB-6 or rituximab indicated that the difference of efficacy was more pronounced at low doses and when target cells expressed fewer CD20 molecules. Thus, EMAB-6 mAb represents a promising drug candidate for the treatment of CLL by inducing a strong cytotoxicity against tumour cells that express low CD20 levels.
  British Journal of Haematology 04/2008; 140(6):635-43. · 4.94 Impact Factor
• Source

  Available from: haematologica-thj.org

  Article: A comparison of the sensitivity of flow cytometry and bone marrow biopsy in the detection of minimal residual disease in chronic lymphocytic leukemia.

  Karim Maloum, Frédéric Charlotte, Marine Divine, Bruno Cazin, Claude Lesty, Hélène Merle-Béral
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  ABSTRACT: We compared the sensitivity of bone marrow biopsy to blood flow cytometry in detecting minimal residual disease (MRD) in 29 patients with chronic lymphocytic leukemia (CLL) in clinical remission after treatment. These results demonstrate that flow cytometry is more sensitive than bone marrow biopsy in detecting MRD and in predicting relapse in CLL.
  Haematologica 07/2006; 91(6):860-1. · 6.42 Impact Factor
• Article: Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia.

  Olivier Tournilhac, Bruno Cazin, Stéphane Leprètre, Marine Diviné, Karim Maloum, Alain Delmer, Bernard Grosbois, Pierre Feugier, Frederic Maloisel, Florence Villard, Bruno Villemagne, Dominique Bastit, Karim Belhadj, Nabi Azar, Mauricette Michallet, Geraud Manhès, Philippe Travade
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  ABSTRACT: Ongoing studies in B-cell chronic lymphocytic leukemia are evaluating autologous peripheral blood stem cell (PBSC) transplantation in first remission following fludarabine therapy. However, fludarabine could impair PBSC harvest. In 38 patients after frontline oral fludarabine and cyclophosphamide (FDR-CY) therapy, we prospectively evaluated steady state filgrastim- or lenograstim-primed PBSC mobilization to collect 2.0 x 106/kg or more CD34 cells. The first mobilization, performed a median of 178 days (range, 69-377 days) from the last FDR-CY course, was unsuccessful in 32 patients. This result was significantly associated with a low platelet count before mobilization but not with age, interval from last FDR-CY course, initial stage, remission status, or other blood parameters. Finally, after 1, 2, and 3 mobilizations in 27, 10, and 1 patients, 2.0 x 106/kg or more CD34 cells were collected in only 12. Explorations of the mechanism of poor mobilization and adaptation of PBSC harvest policies after fludarabine treatment are therefore warranted.
  Blood 02/2004; 103(1):363-5. · 9.90 Impact Factor
• Article: Prognostic factors in Waldenstrom's macroglobulinemia: description of the complications during the evolution-preliminary results on 101 patients.

  Laure Stalnikiewicz, Isabelle Carrotte-Lefebvre, Laurence Detourmignies, Christian Rose, Bruno Cazin, Véronique Leblond, Pierre Morel
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  ABSTRACT: Data on clinical features observed in patients with Waldenstrom's macroglobulinemia (WM) during follow-up remain limited. Therefore, we evaluated 860 follow-up procedures in 101 patients. Median age was 66 years and 5-year overall survival 72%, with a median follow-up of 36 months in surviving patients. Sixteen patients presented at diagnosis with two or three cytopenias lasting for at least 3 months (multiple cytopenias [MC]), and MC improved after treatment in eight patients, 4 to 18 months later. MC was observed during at least 6 consecutive months in 23 other patients, 2 to 73 months (median, 24) after diagnosis. MC occurred off-therapy in 12 patients, and on-therapy in 11. Regression occurred in three of the former patients, and in seven of the latter (6 to 24 months after completion of treatment; median, 7). Finally, the 4-year estimated cause-specific cumulative incidence was 40% in the 101 patients. A second malignancy was observed in 11 patients, histological transformation in three, and rapid rise of M-component in only six patients. In conclusion, the present analysis pointed out a high incidence of long lasting MC during the evolution of WM, and a low frequency of rapid rise of M component.
  Seminars in Oncology 05/2003; 30(2):216-9. · 3.50 Impact Factor