N Brousse

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (445)2193.33 Total impact

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    ABSTRACT: Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymphocytes is characterized by lymphoproliferation, autoimmunity, but also an increased risk of invasive bacterial infection, notably following splenectomy. We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found that 12 (10 splenectomized) had experienced 23 invasive bacterial infections mainly caused by Streptococcus pneumoniae. This vulnerability was associated with evidence of defective B-cell function characterized by low serum IgM, low IgM antibody production in response to S.pneumoniae following non-conjugated immunization and low blood memory B-cells counts (including marginal zone (MZ) B-cell counts). This immunodeficiency strongly correlated with intensity of lymphoproliferation. Spleen sections from nine ALPS patients revealed double-negative T-cell (DN-T) infiltration of the MZ, which was depleted of B-cells. MZ in ALPS patients contained an abnormally thick layer of MAdCAM-1 (+) stromal cells and an excess of DN-T cells. DN-T were shown to express MAdCAM-1 ligand, alpha4-beta7 integrin. These observations suggest that accumulating DN T-cells are trapped within stromal cell meshwork and interfere with correct localization of MZ B-cells. Similar observations were made in spleen of fas-deficient mice. Our data revealed an unexpected mechanism by which ALPS results in antipolysaccharide IgM antibody production specific defect. Splenectomy should be avoided.
    Blood 06/2014; · 9.06 Impact Factor
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    ABSTRACT: Crohn disease is an inflammatory bowel disease (IBD) with a complex mode of inheritance. Although nucleotide binding and oligomerization domain containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease remains unknown in the majority of the cases. X-linked inhibitor of apoptosis (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has been reported in some XIAP-deficient patients.
    The Journal of allergy and clinical immunology. 06/2014;
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    ABSTRACT: Background Lymphomatoid Papulosis (LyP) is an uncommon cutaneous T-cell lymphoproliferative disorder (CTLPD) rarely encountered in children.Objective: To specify characteristics of paediatric LyP and to describe both diagnostic difficulties and course of the disease with the experience of 10 years follow up.Patients and Methods This was a retrospective, single-center study of twenty-five children diagnosed with LyP according to the 2008 World Health Organization guidelines, and a clinical and pathological correlation by two experts.ResultsThe mean age at the onset was 7y 6m. The lesions were mostly papulonodular with frequent pruritus (40%). A mucosal involvement could be observed. A single ulcerate nodule was initially suggestive of a primary cutaneous anaplastic large cell lymphoma (C-ALCL). Pityriasis lichenoides was associated in 36% of cases, atopic dermatitis in 28% and non specific infections in 28%. Complete remission was observed in 44% of cases. Through the mean follow-up of 10 years,none of our patients have experienced lymphoma occurence. Histopathologic subtype A clearly predominated (82%). A marked eosinophilic infiltrate was present in 44% and a cutaneous T gamma clone in 40%. No correlation was observed between histopathologic subtype, cutaneous clone or LyP clinical course.Limitations: retrospective studyConclusion Paediatric LyP belongs to CD30-positive CTLPD including C-ALCL. Children have to be carefully life-long followed-up even if the prognosis appears good. The high frequency of an associated viral infection, atopic dermatitis, marked eosinophilic infiltrate and a good outcome suggests that paediatric LyP could be considered as a reactional disease rather than a malignant disorder.This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 04/2014; · 3.76 Impact Factor
  • Journal of Clinical Oncology 02/2014; · 18.04 Impact Factor
  • Julie Bruneau, Nicole Brousse
    La Revue du praticien 02/2014; 64(2):265-71; quiz 272.
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    ABSTRACT: Detection of MUM1+ cells in follicular lymphoma (FL) tissues was previously found to be associated with poor prognosis in a single report; whereas the usefulness of Ki67 immunostaining remains debated. Our goal was to establish whether these markers have predictive value for FL patients. We analyzed MUM1 and Ki67 expression using immunohistochemistry (IHC) in biopsy samples from 434 patients from the PRIMA randomized trial. The MUM1 prognostic value was then validated in a cohort of 138 patients from the FL2000 randomized trial, using the optimal cut-off value obtained from the PRIMA cohort. The surface of positive staining was quantified using computerized image analysis (CIA). In the PRIMA cohort, both high levels of MUM1 positivity (cut-off value of 0.80%) and high levels of Ki67 positivity (cut-off value of 10.25%) were significantly associated with a shorter progression free survival (PFS) (P=.004 and P=.007 for MUM1 and Ki67, respectively). In a multivariate Cox proportional hazards regression model, only MUM1 retained a statistical significance (HR=1.56, 95% CI 1.02-2.37, P=.038) after adjustment for the maintenance arm of treatment and the FLIPI score. In the FL2000 cohort, high levels of MUM1 positivity were significantly associated to a shorter PFS (P=.004) and to a trend toward a shorter overall survival (OS) (P=.043). This remained significant using a multivariate Cox regression model after adjustment for the FLIPI and the treatment arm for PFS (P=.016). These results show that MUM1 is a strong and robust predictive IHC marker in FL patients.
    Human pathology 01/2014; · 3.03 Impact Factor
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    ABSTRACT: Little is known about intestinal CD4+ T-cell lymphoma; this rare malignancy is frequently misdiagnosed. We evaluated diagnostic criteria and factors that might affect its development and outcome. In a retrospective analysis, we analyzed medical records and intestinal specimens from 10 patients diagnosed with intestinal CD4+ T-cell lymphoma among 115 consecutive patients examined for severe enteropathy with villous atrophy. Samples were analyzed by histology, flow cytometry, and comparative genomic hybridization. Small intestine epithelial and lamina propria tissues from patients who presented with chronic diarrhea and malnutrition had variable levels of infiltration of the by CD3+ CD4+ T cells. Flow cytometry revealed a high frequency of CD4+ intra-epithelial cells, which frequently expressed a specific Vβ chain. T-cell receptor β clonality was confirmed by DNA sequencing. Two patients had HLA and serology results compatible with celiac disease and autoimmune enteropathy, respectively. Two patients were found to have antibodies against human T-cell leukemia virus and 2 patients had signs of recent infection with herpes viruses. Comparative genomic hybridization analyses showed heterogeneous chromosomal abnormalities. Symptoms were reduced in patients treated with steroids (n=5), but not in patients given purine analogues or chemotherapy. Antibodies against CD52 produced clinical and histological responses in 2/2 patients, whereas severe adverse effects developed in 1 patient. At the latest follow up, all patients are alive. There is much heterogeneity in onset and genetic features of intestinal CD4+ T cell lymphomas, despite their common presentation as indolent lymphoproliferations of the intestinal mucosa. Patients should be treated with steroids, and possibly antibodies against CD52 (for the most aggressive forms of this disorder).
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2013; · 5.64 Impact Factor
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    ABSTRACT: Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain-7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development.
    The Journal of clinical investigation 12/2013; · 15.39 Impact Factor
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    ABSTRACT: Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.
    Human Genetics 10/2013; · 4.63 Impact Factor
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    ABSTRACT: Monogenic interleukin (IL)-10 and IL-10 receptor (IL-10R) deficiencies cause very early-onset, severe inflammatory bowel disease. Here, we report that five patients with an IL-10R1 (n=1) or IL-10R2 (n=4) deficiency developed B cell non-Hodgkin's lymphoma between the ages of 5 and 6 years (which were recurrent in one patient). These lymphomas had some of the characteristics of diffuse large B cell lymphomas and contained monoclonal, Epstein-Barr-virus-negative germinal center B cells. The tumors displayed a remarkably homogeneous signature, with original activation of the NF-κB pathway and a decrease in intratumor T cell infiltration. Hence, IL-10R deficiency is associated with a high risk of developing B cell lymphoma. Our results revealed an unexpected role of the IL-10R pathway in lymphomagenesis.
    Blood 10/2013; · 9.06 Impact Factor
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    ABSTRACT: Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow-up (ie > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high-tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy-based regimen plus rituximab and outcome was updated. With a median follow-up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary endpoint) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P<0.0001 and P=0.001 respectively). Considering long-term toxicity, the addition of rituximab in first line setting was confirmed as safe with regards to secondary malignancies development. Long-term follow-up of patients with follicular lymphoma treated in the FL2000 study confirms the sustained clinical benefit of rituximab without long-term toxicity. This study was registered at ClinicalTrials.gov number NCT00136552.
    Haematologica 05/2013; · 5.94 Impact Factor
  • V. Verkarre, N. Brousse
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    ABSTRACT: Coeliac disease is a common disease, affecting 1% of the population. Clinical manifestations are multiple. The diagnosis requires serologic testing and a duodenal biopsy that shows the characteristic findings of intraepithelial lymphocytosis, crypt hyperplasia and villous atrophy, and a positive response to a gluten-free diet. In most patients, the histological diagnosis is easily established. Pitfalls in the pathological diagnosis include a poorly orientated biopsy specimen, either an inadequate biopsy sampling in patients with patchy villous atrophy and the other causes of villous atrophy. A non-response to the gluten-free diet needs to reassess first, the initial diagnosis, second to be sure of the gluten-free diet adherence, and third, to exclude malignant complications such as refractory celiac disease or enteropathy-associated T-cell lymphoma.
    Fuel and Energy Abstracts 04/2013;
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    ABSTRACT: INTRODUCTION: Prognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma. PATIENTS AND METHODS: Medical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan-Meier curves with Logrank test and Cox Model. RESULTS: Lymphoma complicated non clonal enteropathy, celiac disease (n=15) and type I refractory celiac disease (n=2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level>21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p=0.0007, p<0.0001, p<0.0001, p<0.0001, respectively). In multivariate analysis, serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p<0.002, p<0.03, p<0.03, respectively). CONCLUSIONS: Our study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival.
    Digestive and Liver Disease 01/2013; · 3.16 Impact Factor
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    ABSTRACT: Background Late-onset post-transplantation lymphoproliferative disorders (PTLDs) occur 1 year after transplantation and are associated with poor prognosis. Initial treatment usually involves a reduction in immunosuppressive treatment. While early-onset PTLDs have a good prognosis following RI, this approach is generally inadequate for late-onset PTLDs. We assessed the specific outcome of late-onset PTLDs after kidney transplantation during the past three decades.Methods We reviewed the clinical and biological data of 52 kidney transplant recipients who developed late-onset PTLDs at our centre between 1980 and 2010. We compared clinical features, long-term outcome and renal prognosis of late-onset PTLDs both before and after the era of rituximab.ResultsBefore 2000, 38% of the patients underwent surgery and 76% received chemotherapy either immediately or after surgery. After 2000, rituximab was administrated to 70% of the patients either alone (23%) or in combination with chemotherapy (77%). Chemotherapy alone was administrated in 26% of the cases. Before and after 2000, complete remission was achieved in 38 and 87% of the cases, respectively (P = 0.0005). The 5-year overall survival (OS) was 33.3 and 69% (P = 0.003), and 5-year disease-free survival was 37.5 and 80%, respectively (P = 0.19). Renal function was preserved in 70% of the cases at the end of the follow-up.Conclusions This study shows an increase in OS and low graft loss for patients with late-onset PTLDs during the last decade, which may be attributed to multiple changes in clinical practice, including a more standardized treatment and the use of rituximab in combination with chemotherapy.
    Nephrology Dialysis Transplantation 11/2012; · 3.37 Impact Factor
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    ABSTRACT: Disseminated bacillus Calmette-Guérin infection (BCGitis) is an uncommon condition which is usually associated with primary immunodeficiency. Skin histopathology findings have been described in rare cases only. A retrospective clinicopathological study was performed to assess the potential utility of skin biopsies in the diagnosis, prognosis and follow-up of these patients. Four cases of disseminated BCGitis in children with Severe Combined ImmunoDeficiency were biopsied before and after Haematopoietic Stem Cell Transplantation (HSCT). The results were compared to the clinical and immunological status of the children. Early skin biopsies revealed either dense dermal infiltration by foamy macrophages filled with acid fast bacilli (AFB) or mycobacterial spindle-cell pseudotumors rich in AFB. There were no granulomas. These patterns led to the diagnosis of disseminated BCGitis potentially caused by severe immunodeficiency. After HSCT, repeated skin biopsies were performed on persistent or new cutaneous lesions to rule out immune reconstitution inflammatory syndrome and to check for tuberculoid granulomas. One patient died of BCGitis combined with graft versus host disease. The 3 others presented with progressive-onset well differentiated granulomas over a long period and recovered. Skin biopsy is a useful part of the diagnostic workup for disseminated BCGitis, directing the clinician toward severe immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring immune restoration for prognostic purposes.
    Journal of Cutaneous Pathology 10/2012; · 1.77 Impact Factor
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    ABSTRACT: BACKGROUND: Signals emanating from the antigen T-cell receptor (TCR) are required for T-cell development and function. The T lymphocyte-specific protein tyrosine kinase (Lck) is a key component of the TCR signaling machinery. On the basis of its function, we considered LCK a candidate gene in patients with combined immunodeficiency. OBJECTIVE: We identify and describe a child with a T-cell immunodeficiency caused by a homozygous missense mutation of the LCK gene (c.1022T>C) resulting from uniparental disomy. METHODS: Genetic, molecular, and functional analyses were performed to characterize the Lck deficiency, and the associated clinical and immunologic phenotypes are reported. RESULTS: The mutant LCK protein (p.L341P) was weakly expressed with no kinase activity and failed to reconstitute TCR signaling in LCK-deficient T cells. The patient presented with recurrent respiratory tract infections together with predominant early-onset inflammatory and autoimmune manifestations. The patient displayed CD4(+) T-cell lymphopenia and low levels of CD4 and CD8 expression on the T-cell surface. The residual T lymphocytes had an oligoclonal T-cell repertoire and exhibited a profound TCR signaling defect, with only weak tyrosine phosphorylation signals and no Ca(2+) mobilization in response to TCR stimulation. CONCLUSION: We report a new form of T-cell immunodeficiency caused by a LCK gene defect, highlighting the essential role of Lck in human T-cell development and responses. Our results also point out that defects in the TCR signaling cascade often result in abnormal T-cell differentiation and functions, leading to an important risk factor for inflammation and autoimmunity.
    The Journal of allergy and clinical immunology 09/2012; · 12.05 Impact Factor
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    ABSTRACT: Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis (LCH). We investigated the frequency of BRAF mutations in several types of histiocytoses. Histology from 127 patients with histiocytoses were reviewed. Detection of BRAF(V600) mutations was performed by pyrosequencing of DNA extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma, xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients, respectively. BRAF status was obtained in 93 cases. BRAF(V600E) mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses. Four patients with ECD died of disease. The high frequency of BRAF(V600E) in LCH and ECD suggests a common origin of these diseases. Treatment with vemurafenib should be investigated in patients with malignant BRAF(V600E) histiocytosis.
    Blood 08/2012; 120(13):2700-3. · 9.06 Impact Factor
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    ABSTRACT: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.
    Annals of Oncology 07/2012; 23(9):2380-5. · 7.38 Impact Factor
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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; · 9.06 Impact Factor
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    ABSTRACT: Tumor-associated macrophages (TAMs) might be associated with worse outcome in classical Hodgkin lymphoma (cHL). Our aim was to determine whether TAMs correlated with refractoriness in cHL. In a cohort of 18 consecutive primary refractory or early relapsed cases and 41 randomly selected controls (responder patients), high TAM infiltration was significantly associated with refractoriness or early relapse (p = 0.004) and remained independently correlated with outcome in multivariate analysis (odds ratio 8.276, 95% confidence interval 1.214-56.408). This study provides evidence that the marker CD68 might accurately predict early outcome of de novo cHL and could be used in combination with c-kit and TiA1 staining.
    Leukemia & lymphoma 06/2012; · 2.40 Impact Factor

Publication Stats

12k Citations
2,193.33 Total Impact Points

Institutions

  • 1999–2014
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
    • Institut Curie
      Lutetia Parisorum, Île-de-France, France
  • 1996–2014
    • Université René Descartes - Paris 5
      • • Faculty of medicine
      • • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Université Paris-Sorbonne - Paris IV
      Lutetia Parisorum, Île-de-France, France
  • 2007–2013
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 2008–2011
    • Université Paris Descartes
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 1989–2009
    • Centre Hospitalier Lyon Sud
      Lyons, Rhône-Alpes, France
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2001–2007
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier de Lens
      Lens, Nord-Pas-de-Calais, France
  • 2003
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 2000
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 1991
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1988
    • Institut Jean-Godinot
      Rheims, Champagne-Ardenne, France