V Leblond

Universität Ulm, Ulm, Baden-Wuerttemberg, Germany

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Publications (167)898.59 Total impact

  • [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; · 3.02 Impact Factor
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    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. · 6.19 Impact Factor
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    ABSTRACT: ABSTRACT Enzastaurin is an oral serine/threonine kinase inhibitor of the protein kinase C (PKC) and PI3 kinase/Akt pathways pathway that induced apoptosis in multiple myeloma (MM) cell lines in a caspase-independent manner. A phase II study was conducted to assess response rate, time to progression (TTP), safety, and biomarker association with clinical outcomes after monotherapy with the PKC inhibitor enzastaurin in previously treated patients with MM. Eligible patients (N = 14) were treated with enzastaurin 250 mg twice daily after receiving loading doses on day 1. One minimal response was observed. The median TTP was 5.11 months. There were two grade 3 adverse events, anemia and prolonged QTc interval, and no grade 4 adverse events. Single-agent enzastaurin was well tolerated but not effective in this heavily pretreated MM population. ClinicalTrials.gov Identifier NCT00718419.
    Leukemia & lymphoma 11/2013; · 2.61 Impact Factor
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    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. · 8.25 Impact Factor
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    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. · 6.19 Impact Factor
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    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
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    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; · 1.97 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2013; · 10.16 Impact Factor
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    ABSTRACT: Type I cryoglobulinemia vasculitis (CryoVas) is considered a life-threatening condition; however, data on the characteristics and outcome are scarce. To analyze the presentation, prognosis, and efficacy and safety of treatments of type I CryoVas, we conducted a French nationwide survey that included 64 patients with type I CryoVas between January 1995 and July 2010: 28 patients with monoclonal gammopathy of unknown significance (MGUS) and 36 with hematologic malignancy.Type I monoclonal CryoVas was characterized by severe cutaneous involvement (necrosis and ulcers) in almost half the patients and high serum cryoglobulin levels, contrasting with a lower frequency of glomerulonephritis than expected. The 1-, 3-, 5-, and 10-year survival rates were 97%, 94%, 94%, and 87%, respectively. Compared to MGUS, type I CryoVas related to hematologic malignancy tended to be associated with a poorer prognosis. Therapeutic regimens based on alkylating agents, rituximab, thalidomide or lenalinomide, and bortezomib showed similar efficacy on vasculitis manifestations, with clinical response rates from 80% to 86%.Data from the CryoVas survey show that the prognosis of type I CryoVas does not seem to be as poor as previously suggested. Besides alkylating agents, the use of regimens based on rituximab, thalidomide or lenalinomide, and bortezomib are interesting alternative options, although the exact role of each strategy remains to be defined.
    Medicine 03/2013; 92(2):61-68. · 4.35 Impact Factor
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    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; · 4.57 Impact Factor
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    C Buske, V Leblond
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    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; · 10.16 Impact Factor
  • La Revue du praticien 11/2012; 62(9):1192-5.
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    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; · 5.13 Impact Factor
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    ABSTRACT: Background. Waldenström macroglobulinemia is a mature B-cell disease, the genetic bases of which are poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. Design and Methods. We conducted a prospective cytogenetic study of Waldenström macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomised trial. Results. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). Trisomy of chromosomes 4 and 18 were significantly associated. Translocation involving IGH genes was rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival (PFS) and short disease-free survival (DFS). Although rare (<5%), trisomy 12 was associated with short PFS. Conclusions. The cytogenetic profile of Waldenström macroglobulinemia thus appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. The trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374.
    Haematologica 10/2012; · 5.94 Impact Factor
  • Journal de Mycologie Médicale/Journal of Medical Mycology 09/2012; 22(3):276. · 0.74 Impact Factor
  • Journal de Mycologie Médicale / Journal of Medical Mycology. 09/2012; 22(3):276.
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    ABSTRACT: Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. These findings provided the rationale for a multicenter phase II trial of oral enzastaurin in previously treated patients with WM. Experimental design: Patients who were treated with 1 to 5 prior regimens and who had a baseline immunoglobulin M level 2 times or more the upper limit of normal received oral enzastaurin 250 mg twice daily (500 mg total) after a single loading dose (day 1, cycle 1) of 375 mg 3 times daily (1,125 mg total) for 8 cycles of 28 days each or until progressive disease. Six patients who progressed during treatment with enzastaurin had dexamethasone added per protocol. From July 2008 to December 2010, 42 patients were enrolled. The objective response rate (RR) was 38.1% (2 partial and 14 minor responses). One patient had grade 3 leukopenia and one patient died during the study from septic shock; both events were considered drug related. A statistically significant association between RR and interleukin 15 (IL-15) was observed, suggesting that higher concentration levels of IL-15 may be associated with better response. Enzastaurin was active and well tolerated in previously treated patients with WM. Because of the small sample size of this uncontrolled study, further assessment of the relationship between IL-15 and response to enzastaurin in patients with WM is required. These results warrant further investigation of enzastaurin for the treatment of WM. Clin Cancer Res; 18(18); 5043-50. ©2012 AACR.
    Clinical Cancer Research 08/2012; 18(18):5043-50. · 7.84 Impact Factor
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    ABSTRACT: We investigated whether a young human leukocyte antigen (HLA)-matched unrelated donor (MUD) should be preferred as donor to an HLA-identical sibling (MRD) for older patients with myelodysplastic syndrome (MDS) (50 years) who underwent allogeneic stem cell transplantation (AHSCT). Outcomes of 719 MDS patients with a median age of 58 years (range, 50-73 years) who received AHSCT from related (n=555) or unrelated (n=164) donors between 1999 and 2008 and reported to the European Group for Blood and Marrow Transplantation were analyzed. The median donor age of the MRD was 56 years (range: 35-78), in contrast to 34 years (range: 19-64) for the MUDs. Influence of donor's age on survival was not observed for MRD (hazard ratio (HR): 1.01 (95% confidence interval (CI): 0.99-1.02), P=0.2), but there was a significant impact of MUD's age on outcome (HR: 1.03 (95% CI: 1.01-1.06); P=0.02). Transplantation from younger MUDs (<30 years) had a significant improved 5-year overall survival in comparison with MRD and older MUDs (>30 years): 40% vs 33% vs 24% (P=0.04). In a multivariate analysis, AHSCT from young MUD (<30 years) remained a significant factor for improved survival in comparison with MRD (HR: 0.65 (95% CI: 0.45-0.95), P=0.03), which should be considered in donor selection for older patients.Leukemia advance online publication, 21 August 2012; doi:10.1038/leu.2012.210.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2012; · 10.16 Impact Factor
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    ABSTRACT: Neuropathy in Waldenström's macroglobulinemia (WM) is very heterogeneous. We retrospectively studied 40 patients with WM and neuropathy to analyze the different presentations and mechanisms encountered and to propose a diagnostic strategy. Twenty-five patients (62.5%) had axonal neuropathy, related to the following mechanisms: amyloid neuropathy (n = 5), cryoglobulinemic neuropathy (n = 5), neuropathy associated with tumoral infiltration (n = 2), vasculitic neuropathy (n = 2), a clinical motor neuropathy possibly of dysimmune origin (n = 6), or an unclassified mechanism (n = 5). A demyelinating pattern was observed in 15 patients, 10 having anti-myelin-associated glycoprotein (anti-MAG) antibodies and 5 having neuropathy related to chronic inflammatory demyelinating polyradiculoneuropathy. On the basis of these results, we propose a diagnostic strategy combining: (1) an EMG to distinguish between a demyelinating and an axonal pattern; (2) measurement of anti-MAG and anti-ganglioside antibodies; (3) screening for "red flag" features to orientate further investigations. This strategy may help clinicians to identify the mechanism of neuropathy in order to adapt the therapeutic strategy.
    Journal of the Peripheral Nervous System 03/2012; 17(1):90-101. · 2.57 Impact Factor

Publication Stats

3k Citations
898.59 Total Impact Points

Institutions

  • 2013
    • Universität Ulm
      • Institute of Experimental Tumor Research
      Ulm, Baden-Wuerttemberg, Germany
  • 1996–2013
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • • Service de Parasitologie-Mycologie
      • • Service d’Ophtalmologie
      Paris, Ile-de-France, France
    • Paul Scherrer Institut
      Aargau, Switzerland
  • 2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2006–2012
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
  • 2001
    • Centre Hospitalier de Meaux
      Île-de-France, France
  • 2000
    • Centre Hospitalier Universitaire de Nantes
      Naoned, Pays de la Loire, France
    • Cea Leti
      Grenoble, Rhône-Alpes, France
  • 1999
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1998
    • Unité Inserm U1077
      Caen, Lower Normandy, France