V Leblond

CHU Sainte-Justine, Montréal, Quebec, Canada

Are you V Leblond?

Claim your profile

Publications (159)867 Total impact

  • Journal de Mycologie Médicale/Journal of Medical Mycology 06/2015; 25(2). DOI:10.1016/j.mycmed.2015.02.015 · 0.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tailoring treatment by patient strata based on the risk of disease progression and treatment toxicity might improve outcomes of patients with posttransplant lymphoproliferative disorder (PTLD). We analysed the cohort of 70 patients treated in the international, multicenter phase II PTLD-1 trial (NCT01458548) to identify such factors. Of the previously published scoring systems in PTLD, the international prognostic index (IPI), the PTLD prognostic index and the Ghobrial score were predictive for overall survival. None of the scoring systems had a considerable effect on the risk for disease progression. Age and ECOG performance status were the baseline variables with the highest prognostic impact in the different scoring systems. Baseline variables not included in the scoring systems that had an impact on overall survival and disease progression were the type of transplant and the response to rituximab at interim staging. Thoracic organ transplant recipients who did not respond to rituximab monotherapy were at particularly high risk for death from disease progression with subsequent CHOP-based chemotherapy. Patients in complete remission after four courses of rituximab and patients in partial remission with low-risk IPI had a low risk of disease progression. We speculate that chemotherapy might not be necessary in this patient cohort. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 03/2015; 15(4). DOI:10.1111/ajt.13086 · 6.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epstein-Barr virus (EBV) is the etiologic agent of infectious mononucleosis and the root cause of B-cell lymphoproliferative disease in individuals with a weakened immune system, as well as a principal cofactor in nasopharyngeal carcinoma, various lymphomas and other cancers. The EBV major virion surface glycoprotein (gp)350 is viewed as the best vaccine candidate to prevent infectious mononucleosis in healthy EBV-naive persons and EBV-related cancers in at-risk individuals. Previous epitope mapping of gp350 reveals only one dominant neutralizing epitope, which has been shown to be the target of the monoclonal antibody 72A1. Computer modeling of 72A1 antibody interaction with the gp350 amino terminus was used to identify gp350 amino acids that could form strong ionic, electrostatic or hydrogen bonds with the 72A1 antibody. Peptide DDRTTLQLAQNPVYIPETYPYIKWDN (designated as peptide 2) and peptide GSAKPGNGSYFASVKTEMLGNEID (designated as peptide 3) were designed to spatially represent the gp350 amino acids predicted to interact with the 72A1 antibody paratope. Peptide 2 bound to the 72A1 antibody and blocked 72A1 antibody recognition of the native gp350 molecule. Peptide 2 and peptide 3 were recognized by human IgG and shown to elicit murine antibodies that could target gp350 and block its recognition by the 72A1 antibody. This work provides a structural mapping of the interaction between the EBV neutralizing antibody 72A1 and the major virion surface protein gp350. Gp350 mimetic peptides that spatially depict the EBV neutralizing epitope would be useful as a vaccine to focus the immune system exclusively to this important virus epitope. The production of virus-neutralizing antibodies targeting the Epstein-Barr virus (EBV) major surface glycoprotein gp350 is important for the prevention of infectious mononucleosis and EBV-related cancers. The data presented here provide the first in silico map of gp350 interaction with a virus blocking monoclonal antibody. Immunization of gp350 peptides identified by in silico mapping generated antibodies that cross-react with the EBV gp350 molecule and block recognition of the gp350 molecule by a virus neutralizing antibody. Through its ability to focus the immune system exclusively on the gp350 sequence important for viral entry, these peptides may form the basis of an EBV vaccine candidate. This strategy would side-step the production of other irrelevant gp350 antibodies that divert the immune system from generating a protective antiviral response or that impede access to the virus blocking epitope by protective antibodies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of Virology 02/2015; 89(9). DOI:10.1128/JVI.03269-14 · 4.65 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S274-S275. DOI:10.1016/j.annder.2014.09.116 · 0.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Detection of increasing mixed chimerism (IMC) using standard PCR correlates with relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method, which can be performed on peripheral blood. We studied the significance of low increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89 transplants. We did not observe relapse among the 32 patients with no IMC. Fifty-seven patients presented a first IMC, which was followed by four different scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1 relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6 cases, 5 relapses). In multivariate analysis, detection of two successive IMCs was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence interval (CI): 3.8-23; P<0.0001). Among the 57 patients who presented at least one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the 30 other patients (P=0.0007). Altogether, these results indicate that chimerism analysis using indel qrtPCR in peripheral blood is a useful tool for detection of relapse in patients transplanted for AL.Bone Marrow Transplantation advance online publication, 10 November 2014; doi:10.1038/bmt.2014.254.
    Bone Marrow Transplantation 11/2014; 50(2). DOI:10.1038/bmt.2014.254 · 3.47 Impact Factor
  • Source
    Bone Marrow Transplantation 11/2014; 50(2). DOI:10.1038/bmt.2014.243 · 3.47 Impact Factor
  • 19th International Congress of the World-Muscle-Society; 10/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since their introduction in the 2000s, echinocandin drugs have become widely used for the treatment and prophylaxis of invasive fungal infections and, notably, invasive candidiasis. Although cases of breakthrough candidiasis in patients receiving echinocandins have been reported, clinical failure during echinocandin treatment due to the acquisition of resistance by a normally susceptible Candida spp. isolate is considered rare. To date, no publications have been published correlating the use of echinocandins and the emergence of echinocandin resistance among Candida species. So, our goal is to report an initial analysis of echinocandin use in relation to the emergence of resistant Candida isolates. We report here a single-centre experience of the emergence of eight resistant isolates belonging to normally susceptible Candida species in six patients receiving echinocandins. We describe the context and analyse the use of echinocandins over the previous decade. For seven of these isolates, we identified FKS gene mutations involved in decreased susceptibility. Seven isolates were obtained in 2011, on the heels of a ten-fold increase in caspofungin use over the preceding decade. In contrast, in 2012, the use of echinocandins decreased in our institution by 19.5 % and, in that year, only one Candida-resistant isolate was detected, despite the stable global epidemiology of invasive candidaemia. This work underlines the necessity of improving the prescription of antifungal drugs. Improvement in the monitoring of strain susceptibility should also be considered in order to better detect the emergence of resistant or non-susceptible yeast strains.
    European Journal of Clinical Microbiology 04/2014; 33(9). DOI:10.1007/s10096-014-2096-9 · 2.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10(5) copies/mL or primary infection. In the absence of response at 1 month or a viral load >10(6) copies/mL, patients received one rituximab infusion (375 mg/m(2) ). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p = 0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting.
    American Journal of Transplantation 04/2014; 14(4):857-66. DOI:10.1111/ajt.12640 · 6.19 Impact Factor
  • Annals of Oncology 09/2013; 24(suppl 6):vi155-vi159. DOI:10.1093/annonc/mdt298 · 6.58 Impact Factor
  • Journal de Mycologie Médicale/Journal of Medical Mycology 09/2013; 23(3):199. DOI:10.1016/j.mycmed.2013.07.024 · 0.40 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To determine whether rituximab 375 mg/m(2) was efficacious in patients with immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating neuropathy). METHODS: Fifty-four patients with IgM anti-MAG demyelinating neuropathy were enrolled in this randomized, double-blind, placebo-controlled trial. The inclusion criteria were inflammatory neuropathy cause and treatment (INCAT) sensory score (ISS) ≥4 and visual analog pain scale >4 or ataxia score ≥2. The primary outcome was mean change in ISS at 12 months. RESULTS: Twenty-six patients were randomized to a group receiving 4 weekly infusions of 375 mg/m(2) rituximab, and 28 patients to placebo. Intention-to-treat analysis, with imputation of missing ISS values by the last observation carried forward method, showed a lack of mean change in ISS at 12 months, 1.0 ± 2.7 in the rituximab group, and 1.0 ± 2.8 in the placebo group. However, changes were observed, in per protocol analysis at 12 months, for the number of patients with an improvement of at least 2 points in the INCAT disability scale (p = 0.027), the self-evaluation scale (p = 0.016), and 2 subscores of the Short Form-36 questionnaire. CONCLUSIONS:Although primary outcome measures provide no evidence to support the use of rituximab in IgM anti-MAG demyelinating neuropathy, there were improvements in several secondary outcomes in per protocol analysis. LEVEL OF EVIDENCE: This study provides Class I evidence that rituximab is ineffective in improving ISS in patients with IgM anti-MAG demyelinating neuropathy.
    Neurology 07/2013; 80(24):2217. · 8.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We performed a multicenter, International analysis of solid organ transplant (SOT)-related primary central nervous system (PCNS) posttransplant lymphoproliferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT-to-PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBV+ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first-line therapy included high-dose methotrexate (48%), high-dose cytarabine (33%), brain radiation (24%) and/or rituximab (44%). The overall response rate was 60%, while treatment-related mortality was 13%. With 42-month median follow-up, three-year progression-free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high-dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32-5.17, p = 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29-13.46, p = 0.02). Moreover, lack of response to first-line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56-29.57, p = 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.
    American Journal of Transplantation 06/2013; 13(6):1512-22. DOI:10.1111/ajt.12211 · 6.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION L’objectif de l’étude était de décrire les manifestations cliniques et paracliniques des lymphomes extranodaux de la zone marginale (MALT) choroidiens, les difficultés diagnostiques ainsi que les modalités de prise en charge thérapeutique et leur pronostic. MATÉRIELS ET MÉTHODES Il s’agit d’une étude rétrospective concernant neuf cas de lymphome de type MALT choroidiens confirmés histologiquement. Les différentes présentations cliniques ainsi que les données d’imagerie ont été décrites pour chaque patient. Les modalités thérapeutiques, le délai avant la confirmation du diagnostic, les résultats du bilan d’extension et le pronostic de cette affection ont également été évalués. RÉSULTATS La présentation clinique initiale la plus fréquente était la baisse d’acuité visuelle. Les différentes manifestations observées à l’examen clinique étaient les suivantes : sclérite antérieure ou postérieure, uvéite antérieure aigüe, infiltrats choroïdiens, décollement rétinien exsudatif. L’angiographie à la fluorescéine et au vert d’indocyanine tout comme l’OCT ont permis dans chaque cas d’orienter le diagnostic. Les différents sites utilisés pour des biopsies à visée diagnostique étaient : la conjonctive, la capsule de Tenon, le tissu scléral profond, l’épisclère, la glande lacrymale et la choroïde. Le traitement associait le plus fréquemment une chimiothérapie et une radiothérapie. Le délai moyen avant l’établissement du diagnostic était de 12 mois. DISCUSSION Le polymorphisme des signes cliniques et paracliniques des lymphomes de type MALT choroïdiens rend le diagnostic difficile. Dans certains cas, ces lymphomes peuvent simuler d’autres pathologies non tumorales, égarant ainsi le diagnostic et retardant l’initiation du traitement. CONCLUSION En raison de leur présentation clinique initialement progressive et non spécifique, le diagnostic des lymphomes de type MALT choroïdiens est souvent retardé. Néanmoins, le pronostic est habituellement favorable et le traitement efficace dans ces lymphomes localisés.
    SFO; 05/2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PurposeTo describe the clinical and imaging presentation, pitfalls in the diagnosis of choroidal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), as well as the therapeutic management and prognosis.MethodsA retrospective case review of nine choroidal MALT lymphomas was performed. Initial clinical presentation and imaging findings of these histologically confirmed cases of lymphoma were analyzed. Treatment methods, time to diagnosis, systemic work-up, and treatment prognosis were assessed.ResultsInitial presentation was essentially blurred vision. The features described on examination were: anterior and posterior scleritis, iridocyclitis, choroidal infiltration, and exudative retinal detachment. Fluorescein and indocyanine green angiography as well as ultrasonography and optic coherence tomography provided arguments in favor of the diagnosis. Biopsy sites included conjunctiva, Tenon's capsule, deep scleral tissue, episclera, lacrimal gland, and choroid. Treatment mostly consisted of a combination of chemotherapy and radiotherapy. The mean time to diagnosis was 12 months.Conclusions Owing to the insidious onset of these tumors and their ability to simulate other conditions, the diagnosis is commonly delayed. The prognosis is generally good and treatment is effective in the case of localized lymphoma.Eye advance online publication, 19 April 2013; doi:10.1038/eye.2013.74.
    Eye (London, England) 04/2013; 27(7). DOI:10.1038/eye.2013.74 · 1.90 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2013; DOI:10.1038/leu.2013.110 · 9.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Echinocandin drugs are widely used for the treatment of candidemia. Resistance is considered rare and only a few cases of breakthrough candidiasis in patients receiving echinocandin have been reported worldwide. We report here for the first time a Candida kefyr isolate that acquired echinocandin resistance very rapidly after the initiation of caspofungin treatment for candidemia. We characterized the FKS mutation responsible for the resistance via the comparison of isolates sampled before and during treatment.
    Antimicrobial Agents and Chemotherapy 02/2013; 57(5). DOI:10.1128/AAC.02037-12 · 4.45 Impact Factor
  • Source
    C Buske, V Leblond
    [Show abstract] [Hide abstract]
    ABSTRACT: Waldenstrom's macroglobulinemia (WM) is very distinct from other indolent lymphoma subtypes: by definition it is accompanied by a monoclonal IgM gammopathy, it presents always with bone marrow infiltration and often with clinical symptoms such as neuropathy or hyperviscosity. These disease characteristics and the frequently advanced age of the WM patient pose a major challenge to the treating clinician even today. Recently, there has been not only substantial progress in our understanding of the biology of WM, but we have also significantly improved our tools to prognostify and to treat patients with this disease. This review summarizes our current knowledge about WM and aims at offering a guideline for the clinical management of patients with this lymphoma subtype, covering questions how to manage diagnosis, prognostification and treatment based on the most recent data.Leukemia accepted article preview online, 6 February 2013; doi:10.1038/leu.2013.36.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2013; 27(4). DOI:10.1038/leu.2013.36 · 9.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human multidrug resistance-related protein 2 (MRP2, encoded by ABCC2) is involved in the transport of anionic drugs such as methotrexate (MTX). We prospectively investigated the influence of four common ABCC2 genetic variants (rs717620, rs2273697, rs8187694 and rs8187710) on MTX pharmacokinetics parameters. MTX concentrations were monitored in 50 patients with lymphoid malignancy (27 males; mean age: 53±17 years) receiving high-dose MTX (5.13±1.88 g m(-)(2) in a 4-h perfusion). The population pharmacokinetics modelling showed that ABCC2 -24T allele (rs717620) had a combined influence on both MTX elimination and distribution. The MTX clearance and distribution volume were significantly higher in carriers of at least one copy of the -24T allele as compared with noncarriers: 8.6±2.2 vs 6.7± 2.5 l h(-1), P<0.01 and 30.7±7.7 vs 22.1±8.8 l, P<0.001, respectively. Consequently, -24T allele carriers were more prone to reach MTX nontoxic levels, 48 h after administration.The Pharmacogenomics Journal advance online publication, 16 October 2012; doi:10.1038/tpj.2012.37.
    The Pharmacogenomics Journal 10/2012; 13(6). DOI:10.1038/tpj.2012.37 · 5.51 Impact Factor

Publication Stats

4k Citations
867.00 Total Impact Points

Institutions

  • 2015
    • CHU Sainte-Justine
      Montréal, Quebec, Canada
  • 2006–2015
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 1996–2014
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • • Service de Parasitologie-Mycologie
      • • Service d’Ophtalmologie
      Lutetia Parisorum, Île-de-France, France
  • 2008–2012
    • Assistance Publique – Hôpitaux de Paris
      • Department of Neurology
      Lutetia Parisorum, Île-de-France, France
  • 2001–2012
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Foch
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2000
    • Centre Hospitalier Universitaire de Nantes
      Naoned, Pays de la Loire, France
  • 1998
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 1995
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France