Corinne Haioun

Publications (72)560.17 Total impact

• Article: An international confirmatory study of the prognostic value of early PET/CT in diffuse large B-cell lymphoma: comparison between Deauville criteria and ΔSUVmax.

  Emmanuel Itti, Michel Meignan, Alina Berriolo-Riedinger, Alberto Biggi, Amanda F Cashen, Pierre Véra, Hervé Tilly, Barry A Siegel, Andrea Gallamini, René-Olivier Casasnovas, Corinne Haioun
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  ABSTRACT: PURPOSE: The role of interim PET/CT in guiding therapeutic strategies in diffuse large B-cell lymphoma (DLBCL) is debated, mainly because interpretation rules vary among centres. This study aimed to explore the reproducibility and confirm the prognostic value of early PET/CT using the Deauville criteria and ΔSUVmax. METHODS: This international confirmatory study retrospectively evaluated 114 patients with newly diagnosed DLBCL treated with a rituximab-containing regimen. All patients underwent (18)F-FDG PET/CT at baseline (PET0) and after two cycles (PET2), with no therapy change based on the latter. Scans were interpreted by three observers using the Deauville five-point scale and ΔSUVmax between PET0 and PET2 was calculated. Interpretations were evaluated for interobserver agreement and for progression-free survival (PFS) prediction. RESULTS: Median follow-up was 39 months. Early PET/CT was predictive of outcome when interpreted with the Deauville criteria and ΔSUVmax. Using the five-point scale, the overall kappa value was 0.66 with the reference background set in the liver (score ≥4) and interobserver agreement was even better using a 66 % ΔSUVmax cut-off (κ = 0.83). Moreover, the prognostic value of interim PET was slightly inferior when using a Deauville score ≥4 than when using a 66 % ΔSUVmax cut-off: for the Deauville score the 3-year PFS estimate was 59 % (45-73 %) in PET2-positive patients vs. 81 % (71-91 %) in PET2-negative patients (P = 0.003); for the 66 % ΔSUVmax cut-off the 3-year PFS estimate was 44 % (23-65 %) in PET2-positive patients vs. 79 % (70-88 %) in PET2-negative patients (P = 0.0002). CONCLUSION: Although the Deauville criteria are valid for assessing the prognostic value of early PET/CT in DLBCL, computation of the ΔSUVmax leads to better performance and interobserver reproducibility, and should be preferred when a baseline scan is available.
  European Journal of Nuclear Medicine 05/2013; · 4.53 Impact Factor
• Article: Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial.

  Richard Delarue, Hervé Tilly, Nicolas Mounier, Tony Petrella, Gilles Salles, Catherine Thieblemont, Serge Bologna, Hervé Ghesquières, Maya Hacini, Christophe Fruchart, Loïc Ysebaert, Christophe Fermé, Olivier Casasnovas, Achiel Van Hoof, Antoine Thyss, Alain Delmer, Olivier Fitoussi, Thierry Jo Molina, Corinne Haioun, André Bosly
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  ABSTRACT: BACKGROUND: Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become the standard of care for elderly patients with diffuse large B-cell lymphoma. We aimed to ascertain if a dose-dense R-CHOP regimen administered every 2 weeks (R-CHOP14) was superior to the standard 3-week schedule (R-CHOP21). METHODS: We did a randomised phase 3 trial at 83 centres in four countries. 602 patients aged 60-80 years with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor (age-adjusted international prognostic index ≥1) were eligible for the study. We randomly allocated individuals to R-CHOP-ie, rituximab (375 mg/m(2)), cyclophosphamide (750 mg/m(2)), doxorubicin (50 mg/m(2)), vincristine (1·4 mg/m(2), up to 2 mg) all on day 1, and prednisone 40 mg/m(2) daily for 5 days-administered every 14 days (n=304) or every 21 days (n=298) for eight cycles. We did permuted-block randomisation (block size four, allocation ratio 1:1) stratified by centre and number of adverse prognostic factors. The primary endpoint was event-free survival. Our analysis was of the intention-to-treat population, and we present the final analysis. This study is registered with ClinicalTrials.gov, number NCT00144755. FINDINGS: Two patients allocated R-CHOP21 were ineligible for the study and were excluded from analyses. After median follow-up of 56 months (IQR 27-60), 3-year event-free survival was 56% (95% CI 50-62) in the R-CHOP14 group and 60% (55-66) in the R-CHOP21 group (hazard ratio 1·04, 95% CI 0·82-1·31; p=0·7614). Grade 3-4 neutropenia occurred in 224 (74%) of 304 patients allocated R-CHOP14 and 189 (64%) of 296 assigned R-CHOP21, despite increased use of granulocyte colony-stimulating factor in the R-CHOP14 group compared with the R-CHOP21 group. 143 (47%) patients in the R-CHOP14 group received at least one red-blood-cell transfusion versus 93 (31%) in the R-CHOP21 group (p=0·0001). 35 (12%) patients allocated R-CHOP14 received at least one platelet transfusion versus 25 (8%) assigned R-CHOP21 (p=0·2156). 155 (51%) patients who were assigned R-CHOP14 had at least one serious adverse event compared with 140 (47%) who were allocated R-CHOP21. INTERPRETATION: In elderly patients with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor, a 2-week dose-dense R-CHOP regimen did not improve efficacy compared with the 3-week standard schedule. The frequency of toxic side-effects was similar between regimens, but R-CHOP14 was associated with increased need for red-blood-cell transfusion. FUNDING: Groupe d'Etude des Lymphomes de l'Adulte (GELA), Amgen.
  The lancet oncology 04/2013; · 14.47 Impact Factor
• Article: Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups.

  Teresa Marafioti, Christiane Copie-Bergman, Maria Calaminici, Jennifer C Paterson, Vishvesh H Shende, Hongxiang Liu, Maryse Baia, Alan D Ramsay, Claudio Agostinelli, Josette Brière, [......], Simon P Brooks, Asim Khwaja, Kirit Ardeshna, William Townsend, Stefano A Pileri, Corinne Haioun, David Linch, John G Gribben, Philippe Gaulard, Peter G Isaacson
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  ABSTRACT: AIMS: The aim of this study was to analyse the immunophenotypic and molecular features of a large series of follicular lymphomas, focusing in particular on atypical cases that fail to express CD10 and/or bcl-2. Such cases present diagnostic pitfalls, especially with regard to the differential diagnosis from follicular hyperplasia and marginal zone B-cell lymphoma. Therefore, we also included an immunohistochemical evaluation of stathmin, which is strongly expressed by germinal centre B cells, as a putative new marker for follicular lymphomas, particularly those with an atypical phenotype. METHODS AND RESULTS: Two hundred and five follicular lymphomas were investigated with immunohistochemistry and fluorescence in-situ hybridization (FISH). The use of three distinct anti-bcl-2 antibodies together with CD10 expression data and FISH analysis for bcl-2 and bcl-6 rearrangements allowed subclassification of follicular lymphoma into four distinct subgroups: (i) CD10-positive/bcl-2-positive, (ii) CD10-positive/bcl-2-negative, (iii) CD10-negative/bcl-2-positive, and (iv) CD10-negative/bcl-2-negative. All cases were bcl-6-positive. STMN1 (stathmin) was shown to be helpful in diagnosing bcl-2-negative and/or CD10-negative follicular lymphomas, and in their distinction from marginal zone B-cell lymphoma. CONCLUSIONS: Combined immunohistological and molecular analyses reveal that follicular lymphomas showing an atypical immunophenotypic and molecular profile exist, and we demonstrate that STMN1 represents a novel useful diagnostic marker for these.
  Histopathology 03/2013; · 3.08 Impact Factor
• Article: IMMUNOGLOBULIN HEAVY CHAIN/LIGHT CHAIN PAIR MEASUREMENT IS ASSOCIATED WITH SURVIVAL IN DIFFUSE LARGE B-CELL LYMPHOMA.

  Fabrice Jardin, Marie Hélène Delfau-Larue, Thierry Jo Molina, Christiane Copie-Bergman, Josette Brière, Tony Petrella, Danielle Canioni, Bettina Fabiani, Jean-Philippe Jais, Martin Figeac, [......], Sylvain Mareschal, Gilles André Salles, Bertrand Coiffier, Richard Delarue, Frédéric Peyrade, André Bosly, Marc André, Nicolas Ketterer, Corinne Haioun, Hervé Tilly
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  ABSTRACT: Abstract Elevated serum free light chains (FLC) have been associated with unfavorable prognostic in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the clinical relevance of a quantitative assessment of intact circulating immunoglobulin (Ig), using serum Ig heavy chain/light chain pair (HLC) measurements in DLBCL patients. FLC and HLC were measured in 409 serums of DLBCL patients included in the LNH03-B clinical trial program of the GELA. Patients with an abnormal IgMκ/IgMλ ratio or an abnormal FLC ratio more frequently displayed adverse clinical characteristics. Patients with abnormal IgMκ/IgMλ ratios had inferior PFS and OS as compared to patients with normal ratio in the overall cohort (5y-PFS CI95% 44.9 % vs. 69.3%, p =0.0003 and 5y-0S CI95% 50.8% vs. 78.1%, p =0.0003) and in the R-CHOP cohort (5y-0S 43.5% vs. 70.3%, p =0.003). In multivariate analysis including elevated FLC/HLC and IPI, an abnormal IgMκ/IgMλ ratio (HR =1.54, CI95% 1.03-2.3, p =0.03) remained predictive of shorter progression-free survival. Gene expression profile experiments and immunohistochemistry indicate that this measurement is at least partially related to the tumor cell secretion. Both elevated serum FLC and an abnormal IgMκ/IgMλ ratio are associated with unfavorable outcomes in DLBCL patients treated by R-CHOP.
  Leukemia & lymphoma 01/2013; · 2.40 Impact Factor
• Article: Efficacy and toxicity of two schedules of bortezomib in patients with recurrent or refractory follicular lymphoma: A randomised phase II trial from the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

  Vincent Ribrag, Hervé Tilly, Olivier Casasnovas, André Bosly, Reda Bouabdallah, Richard Delarue, François Boue, Dominique Bron, Pierre Feugier, Corinne Haioun, Firtz Offner, Bertrand Coiffier
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  ABSTRACT: PURPOSE: Bortezomib has previously demonstrated activity in indolent lymphomas including follicular lymphoma with response rate ranging from 13% to 56%. However, the optimal schedule of bortezomib remains to be investigated in follicular lymphoma. EXPERIMENTAL DESIGN: We conducted a randomised phase II study where patients with follicular lymphoma in relapse or refractory receive either bortezomib 1.5mg/m(2) biweekly on days 1, 4, 8 and 11 of a 21-day cycle (arm A) or 1.6mg/m(2) weekly on days 1, 8, 15 and 22 of a 35-day cycle (arm B). An interim analysis was planned after 15 fully evaluable patients randomised in each treatment arm. If only five subjects or fewer respond, the treatment arm was concluded to be ineffective and was closed to inclusion. RESULTS: Eighty-seven patients were included in the trial. Arm B was closed to inclusion after interim analysis. 15/50 patients (30%) in arm A and 8/37 patients (22%) in arm B achieved a response. Median duration of response was 16 and 15 months for arms A and B, respectively. Most drug-related adverse events (AEs) (all grades, all cycles) were mild. CONCLUSION: This study demonstrates tolerability and durable clinical benefit of bortezomib when given at 1.5mg/m(2) biweekly. Despite a higher response rate in the biweekly arm, no major difference in patient's outcome was observed between the two arms in the final analysis.
  European journal of cancer (Oxford, England: 1990) 12/2012; · 4.12 Impact Factor
• Article: Follicular Peripheral T-cell Lymphoma Expands the Spectrum of Classical Hodgkin Lymphoma Mimics.

  Julien Moroch, Christiane Copie-Bergman, Laurence de Leval, Anne Plonquet, Nadine Martin-Garcia, Marie-Hélène Delfau-Larue, Valérie Molinier-Frenkel, Karim Belhadj, Corinne Haioun, Josée Audouin, Steven H Swerdlow, Teresa Marafioti, Philippe Gaulard
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  ABSTRACT: Epstein-Barr virus (EBV)-infected B cells with Reed-Sternberg-like cell (RS) features may occur in peripheral T-cell lymphomas (PTCLs), especially in angioimmunoblastic T-cell lymphoma. Here, we report 5 patients presenting with lymphadenopathy whose first biopsies demonstrated nodular lymphoid proliferations containing scattered CD30, CD15, EBV Hodgkin and Reed-Sternberg-like cells, which led to an initial diagnosis of lymphocyte-rich classical Hodgkin lymphoma. However, the uncommon clinical features and/or the occurrence of relapse as PTCL prompted review of the biopsies with expanded immunohistologic and molecular studies and revision of the diagnoses to follicular variant of PTCL (F-PTCL). All cases had atypical small to medium-sized CD3 T cells that expressed CD10 (4/5) and the follicular helper T-cell (TFH) antigens BCL6, PD1, CXCL13, and ICOS. All demonstrated clonal T cells with a similar pattern in multiple samples from 4 patients. In 2 cases, flow cytometry demonstrated circulating lymphocytes with an abnormal sCD3, CD4, ICOS immunophenotype. Two patients had a skin rash at presentation, and 1 had B symptoms. Two of the 4 patients treated with polychemotherapy are alive at 3 and 6 years after first diagnosis. These cases highlight how some F-PTCLs may closely mimic lymphocyte-rich classical Hodgkin lymphoma requiring careful assessment of the T cells before rendering the latter diagnosis. The functional properties of TFH cells might lead to the presence of EBV-positive B blasts with RS-like features in TFH-derived PTCL such as angioimmunoblastic T-cell lymphoma and F-PTCL.
  The American journal of surgical pathology 11/2012; 36(11):1636-1646. · 4.06 Impact Factor
• Article: Impact of [18F]Fluorodeoxyglucose Positron Emission Tomography Response Evaluation in Patients With High-Tumor Burden Follicular Lymphoma Treated With Immunochemotherapy: A Prospective Study From the Groupe d'Etudes des Lymphomes de l'Adulte and GOELAMS.

  Jehan Dupuis, Alina Berriolo-Riedinger, Anne Julian, Pauline Brice, Christelle Tychyj-Pinel, Hervé Tilly, Nicolas Mounier, Andrea Gallamini, Pierre Feugier, Pierre Soubeyran, Philippe Colombat, Guy Laurent, Nathalie Berenger, Rene-Olivier Casasnovas, Pierre Vera, Gaetano Paone, Luc Xerri, Gilles Salles, Corinne Haioun, Michel Meignan
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  ABSTRACT: PURPOSE[(18)F]Fluorodeoxyglucose positron emission tomography (PET) is widely used for the staging and restaging of patients with aggressive lymphoma, but less is known about the utility of PET in patients with follicular lymphoma (FL). In a prospective study, we evaluated the prognostic value of PET performed during treatment and at the end of treatment in 121 patients with FL treated with first-line immunochemotherapy. PATIENTS AND METHODS Patients with previously untreated high-tumor burden FL were treated with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) plus two cycles of rituximab, without rituximab maintenance. PET was performed before treatment, after four cycles of R-CHOP (interim PET), and at the end of treatment (final PET). PET scans were centrally reviewed. RESULTS: 100% versus 88% (P = .0128). CONCLUSIONPET performed either after four cycles of R-CHOP or at the end of therapy was strongly predictive of outcome in this prospective study. Therapeutic intervention based on PET results during or after inductive treatment should be evaluated.
  Journal of Clinical Oncology 10/2012; · 18.37 Impact Factor
• Article: Long-Term Outcome of Adults With Systemic Anaplastic Large-Cell Lymphoma Treated Within the Groupe d'Etude des Lymphomes de l'Adulte Trials.

  David Sibon, Marion Fournier, Josette Brière, Laurence Lamant, Corinne Haioun, Bertrand Coiffier, Serge Bologna, Pierre Morel, Jean Gabarre, Olivier Hermine, Anne Sonet, Christian Gisselbrecht, Georges Delsol, Philippe Gaulard, Hervé Tilly
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  ABSTRACT: PURPOSESystemic anaplastic large-cell lymphoma (ALCL) is a T-cell lymphoma, whose anaplastic lymphoma kinase (ALK) expression varies according to age. Long-term outcomes of chemotherapy-treated adults are not definitively established and should be evaluated. PATIENTS AND METHODS Patients treated in three Groupe d'Étude des Lymphomes de l'Adulte prospective clinical trials with confirmed systemic ALCL after immunohistopathologic review and defined ALK expression status were analyzed.ResultsAmong the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β(2)-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β(2)-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. CONCLUSION Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment.
  Journal of Clinical Oncology 10/2012; · 18.37 Impact Factor
• Article: Rituximab and chlorambucil versus rituximab alone in gastric mucosa-associated lymphoid tissue lymphoma according to t(11;18) status: a monocentric non-randomized observational study.

  Michaël Lévy, Christiane Copie-Bergman, Aurélien Amiot, Jehan Dupuis, Yann Le Baleur, Karim Belhadj, François Hémery, Iradj Sobhani, Marie-Hélène Delfau-Larue, Karen Leroy, Corinne Haioun, Jean-Charles Delchier
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  ABSTRACT: Forty-nine patients, t(11;18)-positive (n = 31) and t(11;18)-negative (n = 18), were treated without randomization with rituximab-chlorambucil or rituximab alone. Evaluation was performed at week (W) 6, week (W) 25 and every 6 months (Wx). Comparing the rituximab-chlorambucil group to the rituximab-alone group, remission was obtained in 93% vs. 66% at W6 (p = 0.01), in 93% vs. 81% at W25 (p = 0.14) and in 93% vs. 76% at Wx (p = 0.07). Comparing the rituximab-chlorambucil group to the rituximab-alone group in t(11;18)-positive patients, remission was obtained in 100% vs. 45% at W6 (p = 0.0005), in 100% vs. 66% at W25 (p = 0.01) and in 96% vs. 55% at Wx (p = 0.01). Comparing the rituximab-chlorambucil group to the rituximab-alone group in t(11;18)-negative patients, remission was obtained in 66% vs. 83% at W6 (p = 0.32), in 66% vs. 92% at W25 (p = 0.22) and in 83% vs. 92% at Wx (p = 0.47). In conclusion, rituximab-chlorambucil is significantly more rapidly efficient than rituximab alone. In t(11;18)-positive patients, the combination is more efficient than rituximab alone. In t(11;18)-negative patients, rituximab alone is as efficient as rituximab-chlorambucil and may be an alternative treatment.
  Leukemia & lymphoma 09/2012; · 2.40 Impact Factor
• Article: Early interim PET scans in diffuse large B-cell lymphoma: can there be consensus about standardized reporting, and can PET scans guide therapy choices?

  Rene-Olivier Casasnovas, Michel Meignan, Alina Berriolo-Riedinger, Emmanuel Itti, Damien Huglo, Corinne Haioun, Franck Morschhauser
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  ABSTRACT: The prognosis value of interim positron emission tomography (PET) remains controversial in diffuse large B-cell lymphoma (DLBCL) patients because of the absence of consensus on criteria able to early identify good and bad responders to treatment. Visual interpretation using the International Harmonization Project (IHP) criteria, primarily established for end of treatment evaluation, was related to a low positive predictive value of treatment failure. The 5-point scale (5PS) that refers the residual uptake to the liver as background tissue was shown to slightly reduce false-positive interim PET interpretations compared to IHP criteria. Semiquantification of fluorodeoxyglucose (FDG) uptake using standardized uptake value (SUV) and assessment of reduction of maximum SUV (SUVmax) between baseline and interim PET drastically improves both the interpretation accuracy and the interobserver reproducibility, and better predicts patient outcome than visual analysis. This latter approach is feasible in a multicenter setting and allows clinicians to design a risk-adapted therapeutic strategy based on early PET response assessment.
  Current Hematologic Malignancy Reports 06/2012; 7(3):193-9.
• Article: Extensive telangiectases of the scalp: atypical presentation of primary cutaneous follicle centre lymphoma.

  Saskia Ingen-Housz-Oro, Meriem Jones, Nicolas Ortonne, Corinne Haioun, Olivier Chosidow
  British Journal of Haematology 06/2012; 158(3):297. · 4.94 Impact Factor
• Article: CHOP and DHAP plus rituximab followed by autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL): a phase II study from the GELA.

  Richard Delarue, Corinne Haioun, Vincent Ribrag, Pauline Brice, Alain Delmer, Herve Tilly, Gilles Salles, Achiel Van Hoof, Olivier Casasnovas, Nicole Brousse, Francois Lefrere, Olivier Hermine
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  ABSTRACT: Treatment of mantle cell lymphoma (MCL) in younger patients remains a challenge. We report results of a phase II trial using Cytarabine and Rituximab (R) as induction regimen before autologous stem cell transplantation (ASCT). Patients under 66y with stage III-IV, MCL were included. Treatment consisted in three courses of CHOP21 with Rituximab at the third one and three R-DHAP. Responding patients were eligible for ASCT with TAM6 or BEAM. Sixty patients were included. Median age was 57 years. Characteristics of patients were: BM involvement 85%, leukemic disease 48%, gastrointestinal involvement 52%, PS>1 6%, LDH>1N 38%, MIPI (low 55%, intermediate 38%, high 13%). ORR was 93% after (R)-CHOP and 95% after R-DHAP. Whereas CR was uncommon after (R)-CHOP (12%), high proportion of patients (57%) was in CR after R-DHAP. With median follow-up of 67 months, median EFS is 83 months and median OS is not reached. Five-year OS is 75%. Comparison with previous study without Rituximab (Lefrere et al., Haematologica 2007) shows improvement of outcome (median EFS: 51 versus 83 months). No toxic death or unexpected toxicities were observed. This study confirms that induction with Rituximab and Cytarabine-based regimens are safe and effective in MCL patients. This regimen is currently compared with R-CHOP21 induction in a multicentric European protocol.
  Blood 06/2012; · 9.90 Impact Factor
• Article: Impact of rituximab on stem cell mobilization following ACVBP regimen in poor-risk patients with diffuse large B-cell lymphoma: results from a large cohort of patients.

  François Lefrère, Dominique Bastit-Barrau, Olivier Hequet, Philippe Bourin, Suzanne Mathieu-Nafissi, Alain Bohbot, Hervé Tilly, Gilles Salles, Christophe Fermé, Valérie Lapierre, Luc Fornecker, Jean-Michel Micléa, Loic Isebaert, Serge Bologna, Olivier Fitoussi, Nicolas Mounier, Corinne Haioun
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  ABSTRACT: BACKGROUND: The ACVBP regimen is an efficient induction regimen for poor-risk patients with diffuse large B-cell lymphoma (DLBCL) before consolidative autologous stem cell transplantation. Adjunction of the monoclonal anti-CD20 antibody rituximab (R-ACVBP) was recently found to be superior to ACVBP alone. This study assessed the impact of rituximab on stem cell mobilization in two similar consecutive groups of patients treated with ACVBP in two prospective, controlled trials. STUDY DESIGN AND METHODS: The first trial (LNH-98B-3) involved 137 patients treated with ACVBP alone. In the second trial (LNH-03-3B), 91 patients received an R-ACVBP regimen. Stem cell mobilization was performed after a course of (R)-ACVBP. RESULTS: The median peak numbers of blood CD34+ cell counts recorded before the first apheresis procedure in the ACVBP and R-ACVBP groups were 69 × 10(6) and 63 × 10(6) /L, respectively (p = 0.55). The median numbers of CD34+ cells collected were 7.1 × 10(6) and 6.0 × 10(6) CD34+ cells/kg for the ACVBP and R-ACVBP groups, respectively (p = 0.13). The median number of apheresis procedures required for gathering the minimum amount of CD34+ cells (2 × 10(6) /kg) was the same in the two groups. CONCLUSION: When compared with ACVBP alone, adjunction of rituximab does not impair stem cell mobilization.
  Transfusion 05/2012; · 3.22 Impact Factor
• Article: Pralatrexate is an effective treatment for relapsed or refractory transformed mycosis fungoides: a subgroup efficacy analysis from the PROPEL study.

  Francine Foss, Steven M Horwitz, Bertrand Coiffier, Nancy Bartlett, Leslie Popplewell, Barbara Pro, Lauren C Pinter-Brown, Andrei Shustov, Richard R Furman, Corinne Haioun, Tony Koutsoukos, Owen A O'Connor
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  ABSTRACT: Transformed mycosis fungoides (tMF) is an aggressive disease with a median survival of 12-24 months. In this retrospective analysis of 12 patients with tMF, treatment with pralatrexate resulted in an objective response of 25% per independent central review and 58% per investigator assessment. Pralatrexate was well tolerated, with no toxicity-related discontinuations, which makes this an additional option for tMF treatment. Transformed mycosis fungoides (tMF) is an aggressive disease, with poor prognosis and a median survival of 24 months. In the Pralatrexate in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PROPEL) study, 12 patients with tMF were treated with a median of 10 pralatrexate doses (starting dose of 30 mg/m(2)) administered weekly for 6 weeks in a 7-week cycle. The median number of prior systemic therapies was 3. This retrospective analysis showed that the objective response rate in this subgroup was 25% (n = 3) per independent central review and 58% (n = 7) per investigator assessment, with this discrepancy likely attributed to challenges with photodocumentation of cutaneous lesions. The median duration of response and the median progression-free survival were 2.2 and 1.7 months, respectively, per central review, whereas median duration of response was 4.4 months, and median progression-free survival was 5.3 months per investigator assessment. Median survival was 13 months. Grade 1-3 mucositis was reported in 7 (58%) patients. Grade 4 adverse events were fatigue (n = 1) and thrombocytopenia (n = 1). Pralatrexate was well tolerated, with no toxicity-related discontinuations. Based on these results, pralatrexate may be a treatment option for patients with relapsed or refractory tMF.
  Clinical lymphoma, myeloma & leukemia 04/2012; 12(4):238-43.
• Article: Report on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 26-27 September 2011 and Menton 2011 consensus.

  Michel Meignan, Andrea Gallamini, Emmanuel Itti, Sally Barrington, Corinne Haioun, Aaron Polliack
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  ABSTRACT: One hundred and ninety-three hemato-oncologists and nuclear medicine specialists from 23 countries joined the 2-day Third International Workshop on Interim Positon Emission Tomography in Lymphoma held in September 2011. Forty scientific posters were presented or discussed in the plenary session. Final results of international validation studies of Deauville criteria and change in maximum standardized uptake value (ΔSUV(MAX)) analysis in Hodgkin lymphoma (HL) as well as non-Hodgkin lymphoma (NHL) were reported. These studies were confirmatory of the prognostic value of interim positron emission tomography (PET) in 261 patients with advanced HL after two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) when reported with the 5-point scale and in 120 patients with diffuse large B-cell lymphoma (DLBCL) after two cycles of a rituximab-containing immunochemotherapy regimen when using ΔSUV analysis. A preliminary consensus on interim PET was established among experts on the assessment of marrow response, refinement of scores 4 and 5 of the 5-point scale, the need to focus on interim PET results for NHL other than DLBCL, methods to compute ΔSUV and factors affecting ΔSUV measurements. Recommendations were given on how to use ΔSUV analysis in NHL taking into account the levels of initial SUV(MAX) and interim SUV(MAX). For the next meeting (October 2012), the majority of the audience strongly favored extending the topics, including in the workshop all aspects of PET in lymphoma, rather than just limiting it to interim PET.
  Leukemia & lymphoma 03/2012; 53(10):1876-81. · 2.40 Impact Factor
• Article: The need for improved neutropenia risk assessment in DLBCL patients receiving R-CHOP-21: findings from clinical practice.

  Antonio Salar, Corinne Haioun, Francesca G Rossi, Ulrich Duehrsen, Ruth Pettengell, Hans E Johnsen, Ulrich Jaeger, Gregor Verhoef, Matthias Schwenkglenks, Pamela Bacon, Kate Bendall, Pieternella J Lugtenburg
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  ABSTRACT: Febrile neutropenia (FN) risk-assessment and granulocyte-colony stimulating factor (G-CSF) prophylaxis use in clinical practice was evaluated in patients with diffuse large B-cell lymphoma receiving R-CHOP-21. More G-CSF primary prophylaxis was used in patients assessed as high FN risk, but R-CHOP-21 was associated with substantial myelotoxicity in both high- and low-risk groups. In a multivariate analysis, older age, poor performance status, lower baseline hemoglobin, and lack of G-CSF prophylaxis were significantly associated with occurrence of FN in any cycle. Results highlight the need for improved FN risk-assessment and thorough guideline adherence to further reduce FN and better support chemotherapy delivery.
  Leukemia research 02/2012; 36(5):548-53. · 2.36 Impact Factor
• Article: Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.

  Marie-Hélène Delfau-Larue, Laurence de Leval, Bertrand Joly, Anne Plonquet, Dominique Challine, Marie Parrens, Alain Delmer, Gilles Salles, Franck Morschhauser, Richard Delarue, Pauline Brice, Reda Bouabdallah, Olivier Casasnovas, Hervé Tilly, Philippe Gaulard, Corinne Haioun
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  ABSTRACT: Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted.
  Haematologica 02/2012; 97(10):1594-602. · 6.42 Impact Factor
• Article: Whole-body diffusion magnetic resonance imaging in the assessment of lymphoma.

  Chieh Lin, Alain Luciani, Emmanuel Itti, Corinne Haioun, Violaine Safar, Michel Meignan, Alain Rahmouni
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  ABSTRACT: The current evidence regarding the usefulness of whole-body diffusion-weighted magnetic resonance imaging (diffusion MRI) in the assessment of lymphoma is reviewed. Diffusion MRI combining both anatomical and bio-physiological information is currently under investigation as a valuable tool in the oncology field including lymphoma, not only for staging but also for the assessment of response. Representative images for each purpose are shown. Diffusion MRI requires no administration of contrast medium and does not use ionizing radiation, which could be particularly advantageous for repeat follow-up surveillance in lymphoma patients. Diffusion MRI may prove to be a useful biomarker in clinical decision making for patients with lymphoma. Large-scale prospective studies are warranted to further establish its complementary value to the current standard of care, [18F]fluorodeoxyglucose positron emission tomography/computed tomography.
  Cancer Imaging 01/2012; 12(2):403-8. · 1.50 Impact Factor
• Article: Interim [18F]fluorodeoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy plus rituximab.

  Violaine Safar, Jehan Dupuis, Emmanuel Itti, Fabrice Jardin, Christophe Fruchart, Stéphane Bardet, Pierre Véra, Christiane Copie-Bergman, Alain Rahmouni, Hervé Tilly, Michel Meignan, Corinne Haioun
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  ABSTRACT: The prognostic value of [(18)F]fluorodeoxyglucose-positron emission tomography (PET), interpreted according to visual criteria, is a matter of debate for diffuse large B-cell lymphoma (DLBCL). Moreover, most published studies do not differentiate between patients treated with or without rituximab. We retrospectively investigated the prognostic value of PET performed in patients with DLBCL receiving chemotherapy plus rituximab. Images were interpreted both visually and by computing maximum standardized uptake value (SUV(max)) between PET performed at baseline and after two cycles of chemotherapy. One hundred twelve patients newly diagnosed with DLBCL were treated with an anthracycline-based regimen plus rituximab. A PET was performed after two cycles of treatment. PET positivity or negativity was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier analysis. Visual analysis showed that 70 patients (62.5%) presented with a negative PET scan after two cycles of treatment. The 3-year PFS and OS rates were 84% and 88%, respectively, in patients with PET-negative results versus 47% and 62%, respectively, in patients with PET-positive results (P < .0001 and P < .003, respectively). A second analysis was performed on 85 patients by using interim PET in a quantitative approach on the basis of a ΔSUV(max) evaluation of more than 66%. The 3-year PFS was 77% for patients with PET-negative results and 37.5% for patients with PET-positive results (P = .002). An early PET scan after two cycles of treatment can effectively predict the outcome in patients with DLBCL treated with rituximab and anthracycline-based chemotherapy by using either a visual or quantitative approach.
  Journal of Clinical Oncology 12/2011; 30(2):184-90. · 18.37 Impact Factor
• Article: Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial.

  Christian Récher, Bertrand Coiffier, Corinne Haioun, Thierry Jo Molina, Christophe Fermé, Olivier Casasnovas, Catherine Thiéblemont, André Bosly, Guy Laurent, Franck Morschhauser, [......], Serge Bologna, Christophe Fruchart, Bernadette Corront, Jean Gabarre, Christophe Bonnet, Maud Janvier, Danielle Canioni, Jean-Philippe Jais, Gilles Salles, Hervé Tilly
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  ABSTRACT: The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable. Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.
  The Lancet 11/2011; 378(9806):1858-67. · 38.28 Impact Factor