Publications by authors named "Louis Terriou"

71 Publications

Systemic Pulmonary Events Associated with Myelodysplastic Syndromes: A Retrospective Multicentre Study.

J Clin Med 2021 Mar 10;10(6). Epub 2021 Mar 10.

Department of Internal Medicine and Clinical Immunology, National Reference Centre for Rare Systemic Autoimmune Disease North and North-West of France, University of Lille, CHU Lille, F-59000 Lille, France.

Although pulmonary events are considered to be frequently associated with malignant haemopathies, they have been sparsely studied in the specific context of myelodysplastic syndromes (MDS). We aimed to describe their different types, their relative proportions and their relative effects on overall survival (OS). We conducted a multicentre retrospective cohort study. Patients with MDS (diagnosed according to the 2016 WHO classification) and pulmonary events were included. The inclusion period was 1 January 2007 to 31 December 2017 and patients were monitored until August 2019. Fifty-five hospitalized patients were included in the analysis. They had 113 separate pulmonary events. Thirteen patients (23.6%) had a systemic autoimmune disease associated with MDS. Median age at diagnosis of MDS was 77 years. Median time to onset of pulmonary events was 13 months. Pulmonary events comprised: 70 infectious diseases (62%); 27 interstitial lung diseases (23.9%), including 13 non-specific interstitial pneumonias and seven secondary organizing pneumonias or respiratory bronchiolitis-interstitial lung diseases; 10 pleural effusions (8.8%), including four cases of chronic organizing pleuritis with exudative effusion; and six pulmonary hypertensions (5.3%). The median OS of the cohort was 29 months after MDS diagnosis but OS was only 10 months after a pulmonary event. The OS was similar to that of the general myelodysplastic population. However, the occurrence of a pulmonary event appeared to be either an accelerating factor of death or an indicator for the worsening of the underlying MDS in our study. More than a third of pulmonary events were non-infectious and could be systemic manifestations of MDS.
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http://dx.doi.org/10.3390/jcm10061162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999053PMC
March 2021

Acquired Hemophilia A in IgG4-Related Disease: Case Report, Immunopathogenic Study, and Review of the Literature.

Front Immunol 2020 18;11:558811. Epub 2020 Dec 18.

CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.

We report the observation of a 75-year-old patient referred for cervical lymphadenopathies. A pre-lymphadenectomy blood work revealed an asymptomatic elevation of aPTT with low factor VIII (FVIII) levels and high anti-FVIII antibodies titers, consistent with acquired hemophilia A (AHA). Histological work-up of a cervical lymphadenopathy revealed benign follicular hyperplasia with IgG4 lymphoplasmacytic infiltration; and serum IgG4 levels were markedly elevated, compatible with IgG4-related disease (IgG4-RD). He was successfully treated with a 9-month course of prednisone, secondarily associated with rituximab when an AHA relapse occurred. As this patient presented with an unusual association of rare diseases, we wondered whether there was a link between the two conditions. Our first hypothesis was that the anti-FVIII autoantibodies could be directly produced by the proliferating IgG4 plasma cells as a result of broken tolerance to autologous FVIII. To test this assumption, we determined the anti-FVIII IgG subclasses in our patient and in a control group of 11 AHA patients without IgG4-RD. The FVIII inhibitor was mostly IgG4, with an anti-FVIII IgG4/IgG1 ratio of 42 at diagnosis and 268 at relapse in our patient; similar values were observed in non-IgG4-RD AHA patients. As a second hypothesis, we considered whether the anti-FVIII activity could be the result of a non-specific autoantibody production due to polyclonal IgG4 plasma cell proliferation. To test this hypothesis, we measured the anti-FVIII IgG4/total IgG4 ratio in our patient, as well as in several control groups: 11 AHA patients without IgG4-RD, 8 IgG4-RD patients without AHA, and 11 healthy controls. We found that the median [min-max] ratio was higher in AHA-only controls (2.4 10 [5.7 10-1.79 10]), an oligoclonal setting in which only anti-FVIII plasma cells proliferate, than in IgG4-RD-only controls (3.0 10 [2.0 10-6.0 10]), a polyclonal setting in which all IgG4 plasma cells proliferate equally. Our patient had intermediate ratio values (2.7 10 at diagnosis and 1.0 10 at relapse), which could plead for a combination of both mechanisms. Although no definitive conclusion can be drawn, we hypothesized that the anti-FVIII autoantibody production in our IgG4-RD AHA patient could be the result of both broken tolerance to FVIII and bystander polyclonal IgG4 plasma cell proliferation.
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http://dx.doi.org/10.3389/fimmu.2020.558811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793697PMC
December 2020

ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder.

Cell Rep Med 2020 Dec 22;1(9):100158. Epub 2020 Dec 22.

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Geographically dispersed patients, inconsistent treatment tracking, and limited infrastructure slow research for many orphan diseases. We assess the feasibility of a patient-powered study design to overcome these challenges for Castleman disease, a rare hematologic disorder. Here, we report initial results from the ACCELERATE natural history registry. ACCELERATE includes a traditional physician-reported arm and a patient-powered arm, which enables patients to directly contribute medical data and biospecimens. This study design enables successful enrollment, with the 5-year minimum enrollment goal being met in 2 years. A median of 683 clinical, laboratory, and imaging data elements are captured per patient in the patient-powered arm compared with 37 in the physician-reported arm. These data reveal subgrouping characteristics, identify off-label treatments, support treatment guidelines, and are used in 17 clinical and translational studies. This feasibility study demonstrates that the direct-to-patient design is effective for collecting natural history data and biospecimens, tracking therapies, and providing critical research infrastructure.
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http://dx.doi.org/10.1016/j.xcrm.2020.100158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762771PMC
December 2020

High dose romiplostim as a rescue therapy for adults with severe bleeding and refractory immune thrombocytopenia.

Am J Hematol 2021 02 23;96(2):E43-E46. Epub 2020 Nov 23.

Department of Internal Medicine, National Referral Center for Adult'Immune Cytopenias Henri Mondor University Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.

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http://dx.doi.org/10.1002/ajh.26040DOI Listing
February 2021

[Crohn's disease and autologous hemapoietic cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

Bull Cancer 2020 Dec 14;107(12S):S140-S150. Epub 2020 Oct 14.

Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France, hôpital St-Louis (AP-HP), unité de médecine interne : maladies auto-immunes et pathologie vasculaire (UF 04), 1, avenue Claude-Vellefaux, 75010 Paris, France; Université Paris-Denis-Diderot, institut de recherche Saint-Louis, EA 3518, Sorbonne Paris Cité, France; McGill University, department of internal medicine, Montreal, Canada. Electronic address:

Crohn's Disease (CD) is an auto-inflammatory disease, which may involve the entire gastro-intestinal tract. CD is diagnosed on several clinical, biological, endoscopic and histological criteria. First line therapy is based on oral or iv steroids. In case of steroids dependence or resistance, several types of immunosuppressive or immunomodulating therapies are available: classical antimetabolites (thiopurines or methotrexate) or monoclonal antibodies against TNFα, against interleukin 12/23 or against integrin. Nonetheless, Crohn's disease may remain active despite the use of several lines of therapy. In such cases, autologous hematopoietic cell transplantation (AHCT) is an effective therapeutic option in highly selected CD patients with specific criteria. The MATHEC-SFGM-TC Good Clinical Practice Guidelines (GCPG) were developed by a multidisciplinary group of experts including gastroenterologists, hematologists and members of the reference center for stem cell therapy in auto-immune diseases (MATHEC), including members of the French groupe d'étude thérapeutique des affections inflammatoires du tube digestif(GETAID) under the auspices of the French speaking Society of bone marrow transplantation and cellular therapy (SFGM-TC). The aim of the present guidelines is to define the eligibility criteria for CD patients when candidates to AHCT, the procedures for mobilization of hematopoietic stem cell (HSC), conditioning regimen and standardized follow-up after AHCT including monitoring of gastroenterological treatments during AHCT and thereafter throughout all follow-up.
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http://dx.doi.org/10.1016/j.bulcan.2020.08.009DOI Listing
December 2020

Vasculitis associated with myelodysplastic syndrome and chronic myelomonocytic leukemia: French multicenter case-control study.

Semin Arthritis Rheum 2020 10 11;50(5):879-884. Epub 2020 Jul 11.

Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France Sorbonne Université, Paris, France; Sorbonne Universités, INSERM U938, Centre de Recherche Saint-Antoine (CRSA), Paris, France. Electronic address:

Introduction: Our objective was to evaluate characteristics, treatment and outcome of vasculitis associated with myelodysplastic syndrome (MDS) and chronic myelomonicytic leukemia (CMML) PATIENTS AND METHODS: Retrospective descriptive analysis of MDS/CMML-related vasculitis and comparison with MDS/CMML patients without dysimmune features.

Results: Seventy patients with vasculitis and MDS/CMML were included, with median age of 71.5 [21-90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/CMML in 31 patients (44%), and after in 20 patients. In comparison with MDS/CMML without autoimmune/inflammatory features, vasculitis with MDS/MPN showed no difference in MDS/CMML subtypes distribution nor International Prognostic Scoring System and CMML-specific prognostic (IPSS/CPSS) scores. Vasculitis subtypes included Giant cell arteritis in 24 patients (34%), Behçet's-like syndrome in 11 patients (20%) and polyarteritis nodosa in 6 patients (9%). Glucocorticoids (GCs) were used as first-line therapy for MDS/CMML vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After a median follow-up of 33.2 months [1-162], 31 patients (44%) achieved sustained remission. At least one relapse occurred in 43 patients (61%). Relapse rates were higher in patients treated with conventional Disease Modifying Anti-Rheumatic Drug (DMARDs) (odds ratio 4.86 [95% CI 1.38 - 17.10]), but did not differ for biologics (odds ratio 0.59 [95% CI 0.11-3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21-9.76]) than under glucocorticoids. Overall survival in MDS/CMML vasculitis was not significantly different from MDS/CMML patients without autoimmune/inflammatory features (p = 0.5), but acute leukemia progression rates were decreased (log rank <0.05).

Conclusion: This study shows no correlation of vasculitis diagnoses with subtypes and severity of MDS/CMML, and no significant impact of vasculitis on overall survival. Whereas conventional DMARDs seem to be less effective, biologics or azacytidine therapy could be considered for even low-risk MDS/CMML vasculitis.
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http://dx.doi.org/10.1016/j.semarthrit.2020.07.002DOI Listing
October 2020

Use of thrombopoietin receptor agonists for immune thrombocytopenia in pregnancy: results from a multicenter study.

Blood 2020 12;136(26):3056-3061

Department of Internal Medicine, National Reference Center for Immune Cytopenias, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Creteil, Créteil, France.

Management of immune thrombocytopenia (ITP) during pregnancy can be challenging because treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are not recommended during pregnancy. To better assess the safety and efficacy of off-label use of Tpo-RAs during pregnancy, a multicenter observational and retrospective study was conducted. Results from 15 pregnant women with ITP (pregnancies, n = 17; neonates, n = 18) treated with either eltrombopag (n = 8) or romiplostim (n = 7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks (range, 1-39 weeks); the indication for starting Tpo-RAs was preparation for delivery in 10 (58%) of 17 pregnancies, whereas 4 had chronic refractory symptomatic ITP and 3 were receiving eltrombopag when pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA-related fetal or neonatal complications were observed, except for 1 case of neonatal thrombocytosis. Response to Tpo-RAs was achieved in 77% of cases, mostly in combination with concomitant ITP therapy (70% of responders). On the basis of these preliminary findings, temporary off-label use of Tpo-RAs for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and is likely to be helpful, especially before delivery.
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http://dx.doi.org/10.1182/blood.2020007594DOI Listing
December 2020

Epidemiology, clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients.

Am J Hematol 2020 11 19;95(11):1314-1323. Epub 2020 Sep 19.

National Reference Center for Hypereosinophilic syndromes (CEREO), Suresnes, France.

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.
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http://dx.doi.org/10.1002/ajh.25945DOI Listing
November 2020

Clinical characteristics, management and outcome of COVID-19-associated immune thrombocytopenia: a French multicentre series.

Br J Haematol 2020 08 4;190(4):e224-e229. Epub 2020 Aug 4.

Department of Internal Medicine, National Referral Center for Adult's Immune Cytopenias Henri Mondor University Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.

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http://dx.doi.org/10.1111/bjh.17024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404899PMC
August 2020

Paraffin Immunofluorescence Increases Light-Chain Detection in Extra-Renal Light Chain Amyloidosis and Other Light-Chain-Associated Diseases.

Arch Pathol Lab Med 2021 03;145(3):352-358

From the Université de Lille, CNRS, Inserm, CHU Lille, Pathology Department, Centre de Biologie Pathologie, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France (Gibier, Gnemmi).

Context.—: Distinguishing the different types of amyloid is clinically important because treatments and outcomes are different. Mass spectrometry is the new gold standard for amyloid typing, but it is costly and not widely available. Therefore, immunolabeling remains the first step in identifying the most common types of amyloidosis. In amyloid subtyping, direct immunofluorescence works well when applied to frozen sections, but immunohistochemistry on formalin-fixed, paraffin-embedded material often yields poor results, particularly for light chain amyloidosis. Recently, paraffin immunofluorescence has been described as a valuable salvage technique in renal pathology when frozen sections are not available but it has not been evaluated for extra-renal diseases.

Objectives.—: To evaluate the use of paraffin immunofluorescence for light-chain detection in extra-renal amyloidosis and other light-chain-associated diseases.

Design.—: First, we compared the staining intensity of both light chains between paraffin immunofluorescence and immunohistochemistry on a retrospective cohort of 28 cases of amyloidosis that have been previously typed. Then, we studied the role of paraffin immunofluorescence as an addition to our classical immunohistochemistry panel for amyloidosis typing.

Results.—: In the retrospective cohort, we found that paraffin immunofluorescence outperformed immunohistochemistry for light-chain detection. Then, in the prospective part of the study, we showed that the proportion of correctly classified cases increased from 50% to 71.9% with the adjunction of second-intention paraffin immunofluorescence to the immunohistochemistry procedure.

Conclusions.—: We therefore view paraffin immunofluorescence as a significant addition to the routine workflow for detection of light-chain-related diseases.
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http://dx.doi.org/10.5858/arpa.2020-0018-OADOI Listing
March 2021

Serious Infectious Events and Immunoglobulin Replacement Therapy in Patients With Autoimmune Disease Receiving Rituximab: A Retrospective Cohort Study.

Clin Infect Dis 2021 Mar;72(5):727-737

University of Lille, Institute for Translational Research in Inflammation (INFINITE), Lille, France.

Background: Rituximab (RTX) is widely administered to patients with autoimmune disease (AID). This study aimed to estimate the incidence of serious infectious events (SIEs) after RTX initiation in patients with AID. We also described the characteristics and risk factors of SIEs, and immunoglobulin replacement therapy (IgRT) strategies.

Methods: Patients treated between 2005 and 2016 were included in this retrospective monocentric cohort study. An RTX course was defined as the complete RTX treatment regimen received by a given patient for AID. SIEs and IgRT were right-censored at 24 months after RTX initiation.

Results: Two hundred twenty-one patients were included (corresponding to 276 RTX courses). Reasons for RTX initiation included connective tissue disease (38%), systemic vasculitis (36%), and autoimmune cytopenia (22%). The 1- and 2-year incidences of SIEs were 17.3 (95% confidence interval [CI], 12.0-22.5) and 11.3 (95% CI, 8.1-14.5) per 100 person-years, respectively. Forty-seven SIEs were observed, mostly comprising pneumonias (45%) and bacteremias (21%). When documented, the microorganisms were bacterial (55%) and fungal (12%). Identified risk factors of SIEs were age, history of diabetes, history of cancer, concomitant steroid treatment, and low CD4 lymphocyte count at RTX initiation. IgRT was started in 22 RTX courses (8%).

Conclusions: In patients with AID treated with RTX, the 1- and 2-year incidence of SIE was 17.3 and 11.3 per 100 person-years, respectively. Reports of SIE characteristics, risk factors, and IgRT strategies highlight the need for an appropriate and individualized assessment prior to and following RTX to prevent SIEs, particularly in patients with comorbidities.
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http://dx.doi.org/10.1093/cid/ciaa127DOI Listing
March 2021

"Idiopathic Eosinophilic Vasculitis": Another Side of Hypereosinophilic Syndrome? A Comprehensive Analysis of 117 Cases in Asthma-Free Patients.

J Allergy Clin Immunol Pract 2020 04 18;8(4):1329-1340.e3. Epub 2019 Dec 18.

Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Lille, France; Hôpital Ambroise Paré, Service de Médecine Interne, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France.

Background: The absence of asthma may rule out a diagnosis of eosinophilic granulomatosis with polyangiitis in patients with hypereosinophilic syndrome (HES) and features of vasculitis.

Objective: To describe eosinophilic vasculitis (EoV) as a possible manifestation of HES in asthma-free patients.

Methods: We screened our hospital database and the literature for patients with HES who met the following 4 criteria: (1) histopathological or clinical features of EoV (biopsy-proven vasculitis with predominant eosinophilic infiltration of the vessel wall and/or features of vasculitis with tissue and/or blood hypereosinophilia [absolute eosinophil count >1.5 G/L]); (2) no other obvious causes of reactive eosinophilia, organ damage, and vasculitis; (3) the absence of antineutrophil cytoplasmic antibodies; and (4) the absence of current asthma.

Results: Ten of our 83 (12%) asthma-free patients with HES and 107 additional cases in the literature met the criteria for EoV. After a critical analysis of the patients' clinical and laboratory characteristics and outcomes, we identified 41 cases of single-organ EoV (coronary arteritis, n = 29; temporal arteritis, n = 8; cerebral vasculitis, n = 4). Of the remaining 76 patients with EoV, the most frequent manifestations (>10%) were cutaneous vasculitis (56%), peripheral neuropathy (24%), thromboangiitis obliterans-like disease (16%), fever (13%), central nervous system involvement (13%), deep venous thrombosis (12%), and nonasthma lung manifestations (12%). Blood hypereosinophilia more than 1.5 G/L was observed in 79% of patients, and necrotizing vasculitis was observed in 44%.

Conclusions: Our results suggest that idiopathic EoV (HES-associated vasculitis) can be classified as an eosinophilic-rich, necrotizing, systemic form of vasculitis that affects vessels of various sizes in asthma-free patients.
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http://dx.doi.org/10.1016/j.jaip.2019.12.011DOI Listing
April 2020

Giant-cell arteritis associated with myelodysplastic syndrome: French multicenter case control study and literature review.

Autoimmun Rev 2020 Feb 13;19(2):102446. Epub 2019 Dec 13.

Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France Sorbonne Université, France; Sorbonne Universités, INSERM U938, Centre de Recherche Saint-Antoine (CRSA), Paris, France. Electronic address:

Introduction: Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN.

Patients And Methods: Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone.

Results: Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42-92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p < .05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p = .07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p < .05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival.

Conclusion: Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse.
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http://dx.doi.org/10.1016/j.autrev.2019.102446DOI Listing
February 2020

[Indication of autologous stem cell transplantation in chronic inflammatory demyelinating polyneuropathy: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

Bull Cancer 2020 Jan 7;107(1S):S104-S113. Epub 2019 Dec 7.

AP-HP, hôpital St-Louis, centre de référence des maladies auto-immunes systémiques rares d'Île-de-France, unité de médecine interne : maladies auto-immunes et pathologie vasculaire (UF 04), 1, avenue Claude Vellefaux, 75010 Paris, France; Institut de recherche Saint-Louis, université Paris Denis Diderot, Sorbonne Paris Cité, EA 3518, Paris, France; Department of Internal Medicine, McGill University, Montreal, Canada. Electronic address:

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure.
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http://dx.doi.org/10.1016/j.bulcan.2019.11.002DOI Listing
January 2020

Assessment of T-cell polarization on the basis of surface marker expression: Diagnosis and potential therapeutic implications in lymphocytic variant hypereosinophilic syndrome.

J Allergy Clin Immunol Pract 2020 Mar 13;8(3):1110-1114.e2. Epub 2019 Sep 13.

Institut d'Immunologie, CHU de Lille, Lille, France; Univ. Lille, U995-LIRIC-Lille Inflammation Research International Center, Lille, France; Département de Médecine Interne, CHU de Lille, Lille, France; Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Lille, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2019.08.049DOI Listing
March 2020

Long-term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP-ritux.

Am J Hematol 2019 12 8;94(12):1314-1324. Epub 2019 Oct 8.

Service de Médecine Interne, Centre National de Référence des Cytopénies Auto-Immunes de l'Adulte, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France.

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.
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http://dx.doi.org/10.1002/ajh.25632DOI Listing
December 2019

Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review.

Front Immunol 2019 28;10:1489. Epub 2019 Jun 28.

Département de Médecine Interne et Immunologie Clinique, CHU Lille, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), LIRIC INSERM U995, Université de Lille, Lille, France.

TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever and/or elevated serum C-reactive protein, renal dysfunction, and organomegaly. A 28-year-old woman with fever, weight gain of 13 kgs, lower extremity edema, hepatosplenomegaly, and multicentric peripheral lymphadenopathy was referred to our center. Laboratory investigations revealed anemia, thrombocytopenia, creatinine at 1.19 mg/dL and hypoalbuminemia at 33 g/L. Proteinuria was measured at 2 g/day including albuminuria at 1.5 g/day. Urinary sediment examination found leukocyturia at 44,000/mL and hematuria at 645,000/mL. Vascular endothelial growth factor (VEGF) level was elevated. A cervical lymph node biopsy found features consistent with the mixed histopathological subtype of iMCD. A renal biopsy revealed a membranoproliferative glomerulonephritis (MPGN) pattern. We initiated 3 days of methylprednisolone pulse-therapy at 1,000 mg per day, followed by prednisone 1 mg/kg/day and evolution was favorable. 19 iMCD patients with TAFRO syndrome had undergone a renal biopsy: 8 cases with author's diagnosis consistent with MPGN-like and 11 cases of thrombotic microangiopathy (TMA)-like glomerulopathy without fibrin thrombi in glomerular capillaries or arterioles and without typical biological signs. Clinical, biological, and outcome characteristics were similar between the cases described as having MPGN and TMA-like presentation. After a thorough review of histopathological descriptions for each case, MPGN lesions seems to be the consequences of chronic glomerular endothelial injury in persistent TMA. We suspect that VEGF and IL-6 play a key role in the physiopathology of the spectrum of renal involvement from TMA-like to MPGN observed in TAFRO syndrome. We present a Caucasian iMCD patient with TAFRO syndrome with renal insufficiency secondary to MPGN, which might be secondary to a chronic TMA-like disease. We suspect that there is a continuum between TMA and MPGN lesions in TAFRO syndrome favored by VEGF and IL-6.
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http://dx.doi.org/10.3389/fimmu.2019.01489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609882PMC
October 2020

Omalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS.

J Allergy Clin Immunol Pract 2019 Sep - Oct;7(7):2387-2395.e3. Epub 2019 Apr 5.

Imagine Institute, INSERM U1163 and CNRS ERL 8654, Paris Descartes University, Sorbonne Paris Cité, Paris, France; Department of Hematology, Necker Children's Hospital, APHP, Paris, France; French Reference Center for Mastocytosis (CEREMAST), Necker Children's Hospital, APHP, Paris, France.

Background: Patients with mast cell diseases may suffer from various distressing symptoms, which can be insufficiently controlled with available therapies, severely affecting their quality of life. There is a need for new and safe treatment options for these patients.

Objectives: We aimed to evaluate safety and efficacy of omalizumab administration in patients with a symptomatic mast cell disorder.

Methods: We included 55 patients with a mast cell disorder associated with debilitating symptoms who received omalizumab treatment between January 2015 and December 2017, after a multidisciplinary team meeting at the French National Reference Center for Mastocytosis.

Results: A complete response was achieved for 1 patient (1.8%), a major response for 30 patients (54.5%), and a partial response for 12 patients (21.8%), resulting in an overall best response rate of 78.2% (43 of 55 patients). The response was persistent at least 3 months in 33 of 43 responding patients (76.7%). At the last follow-up, the final overall response rate was 58.2% (32 of 55 patients). Median time to first response was 2 months and median time to best response was 6 months. Omalizumab was dramatically effective on all superficial and general vasomotor symptoms and on most gastrointestinal or urinary symptoms, and partially effective on most neuropsychiatric symptoms. Safety profile was acceptable, except for one severe adverse event (edema of the larynx and dyspnea after the first injection of omalizumab). Side effects were reported in 16 patients (29%), mainly of low to mild intensity, yet causing interruption of treatment in 5 patients (9%).

Conclusion: Omalizumab seems to be a useful therapeutic option to control mast cell-mediator symptoms and displays a favorable safety profile.
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http://dx.doi.org/10.1016/j.jaip.2019.03.039DOI Listing
October 2020

Nationwide survey in France on the use of romiplostim in patients with refractory severe aplastic anemia.

Bone Marrow Transplant 2019 07 22;54(7):1161-1163. Epub 2019 Jan 22.

Centre de Référence Aplasie Médullaire, Service d'Hématologie Greffe, Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France.

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http://dx.doi.org/10.1038/s41409-019-0452-1DOI Listing
July 2019

Autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease adult patients in France: analysis of the long-term outcome from the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

Clin Rheumatol 2019 May 21;38(5):1501-1511. Epub 2019 Jan 21.

Université Denis Diderot, Paris, France.

Introduction: The use of autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease (AD) patients has increased progressively worldwide. We retrospectively analysed the long-term outcome of AHSCT for AD reported to the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

Method: All French AD patients (≥ 18 years at transplant) with a first AHSCT between 1997 and 2013 were included. Primary data were derived from the European Society for Blood and Marrow Transplantation (EBMT) registry, and additional data were obtained through a specific questionnaire designed for the study. Primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS) and non-relapse mortality (NRM).

Results: Ninety-four AD patients were included, of whom 71% suffered from rheumatologic diseases (n = 67, including 56 systemic sclerosis (SSc)), 16% from neurological disease (n = 15, including 14 multiple sclerosis (MS)) and 13% from various other AD (n = 12). After a median (interquartile range, IQR) follow-up of 83 months (38-130), OS at 5 and 10 years were 77% (95% CI 68.5-86.2) and 64% (95% CI 51.7-76.3), and for PFS 51% (95% CI 40.4-61.6) and 44% (95% CI 32.8-55.3), respectively. Overall, NRM was 8.7% (95% CI 4.0-15.5) at day 100, 9.8% (95% CI 4.8-16.9) at 5 years and 13.6% (95% CI 6.9-22.5) at 10 years.

Conclusions: This first SFGM-TC retrospective report shows long-term benefit of AHSCT in AD patients with acceptable toxicity.
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http://dx.doi.org/10.1007/s10067-019-04435-2DOI Listing
May 2019

[Indications and follow-up for autologous hematopoietic stem cell transplantation in multiple sclerosis: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) in association with the Francophone Society of Multiple Sclerosis].

Bull Cancer 2019 Jan 5;106(1S):S92-S101. Epub 2018 Dec 5.

Hôpital Saint-Louis, centre de référence des maladies auto-immunes systémiques rares d'Île-de-France, filière FAI2R, IUH EA-3518, UF04, unité de médecine interne, maladies auto-immunes et pathologie vasculaire, 1, avenue Claude-Vellefaux, 75475 Paris, France. Electronic address:

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 8th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2017 in Lille, France. In this article we give the indications of autologous stem cell transplantation in multiple sclerosis as well as recommendations regarding post-transplant follow-up of patients under the hospice of the SFGM-TC and the Francophone Society of Multiple Sclerosis.
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http://dx.doi.org/10.1016/j.bulcan.2018.11.002DOI Listing
January 2019

C-Reactive protein as a diagnostic tool in differential diagnosis of hypereosinophilic syndrome and antineutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis.

J Allergy Clin Immunol Pract 2019 Apr 11;7(4):1347-1351.e3. Epub 2018 Oct 11.

CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), University of Lille, Lille, France; Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), France; CHU Lille, Institut d'Immunologie, University of Lille, Lille, France; Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, University of Lille, Lille, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2018.10.002DOI Listing
April 2019

Aplastic anemia in the elderly: a nationwide survey on behalf of the French Reference Center for Aplastic Anemia.

Haematologica 2019 02 27;104(2):256-262. Epub 2018 Sep 27.

French Reference Center for Aplastic Anemia, CHU Saint Louis, Paris.

Aplastic anemia is a rare but potentially life-threatening disease that may affect older patients. Data regarding the treatment of aplastic anemia in this ageing population remains scarce. We conducted a retrospective nationwide multicenter study in France to examine current treatments for aplastic anemia patients over 60 years old. Our aims were to evaluate efficacy and tolerance, and to analyze predictive factors for response and survival. Over the course of a decade, 88 patients (median age 68.5 years) were identified in 19 centers, with a median follow up of 2.7 years; 21% had very severe and 36% severe aplastic anemia. We analyzed 184 treatment lines, mostly involving the standard combination of anti-thymocyte globulin and cyclosporine-A (33%), which was also the most frequent first-line treatment (50%). After first-line therapy, 32% of patients achieved a complete response, and 15% a partial response. Responses were significantly better in first line and in patients with good performance status, as well as in those that had followed an anti-thymocyte globulin and cyclosporine-A regimen (overall response rate of 70% after first-line treatment). All treatments were well tolerated by patients, including over the age of 70. Three-year survival was 74.7% (median 7.36 years). Age, Charlson comorbidity index and very severe aplastic anemia were independently associated with mortality. Age, per se, is not a limiting factor to aplastic anemia treatment with anti-thymocyte globulin and cyclosporine-A; this regimen should be used as a first-line treatment in elderly patients if they have a good performance status and low comorbidity index score.
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http://dx.doi.org/10.3324/haematol.2018.198440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355477PMC
February 2019

International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease.

Blood 2018 11 4;132(20):2115-2124. Epub 2018 Sep 4.

Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti-interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.
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http://dx.doi.org/10.1182/blood-2018-07-862334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238190PMC
November 2018

Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies.

Blood Adv 2018 09;2(17):2176-2185

Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Ravulizumab (ALXN1210), a humanized monoclonal antibody to complement component C5, was engineered from eculizumab to have a substantially longer terminal half-life, permitting longer dosing intervals for paroxysmal nocturnal hemoglobinuria (PNH) treatment. Two phase 1b/2 multicenter open-label studies evaluated efficacy and safety of multiple doses and regimens of ravulizumab in PNH patients naive to complement-inhibitor treatment. Patients in study 103 (n = 13) received ravulizumab 900 mg (lower trough exposure) or 1800 mg every 4 weeks (higher trough exposure); those in study 201 (n = 26) received 1000 mg every 4, 1600 mg every 6, 2400 mg every 8, or 5400 mg every 12 weeks. Trough exposure levels with study 201 dosing regimens were similar to the study 103 900-mg every-4-weeks regimen. Rapid sustained reduction of plasma lactate dehydrogenase (LDH) occurred across all cohorts (73%-90% at end point vs baseline). A greater proportion of patients had normalized LDH (<234 U/L) at least once from days 29 to 253 in the higher- (85.7%) vs lower-trough-exposure (50.0%-83.3%) cohorts; the weighted average of the proportion of instances of LDH normalization from days 29 to 253 was highest in higher- vs lower-trough-exposure cohorts (62.3% vs 31.4%-54.5%). No patients in the higher-trough-exposure cohort, but 1 to 2 patients in all lower-trough-exposure cohorts, experienced breakthrough hemolysis. Ravulizumab improved quality of life (QoL) measures in all cohorts. Two patients experienced meningococcal infections; both recovered and continued in the study. In summary, ravulizumab provided rapid and sustained reduction in complement-mediated hemolysis and improved QoL at dosing intervals up to 12 weeks. This trial was registered at www.clinicaltrials.gov as #NCT02598583 (study 103) and NCT02605993 (study 201).
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http://dx.doi.org/10.1182/bloodadvances.2018020644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134221PMC
September 2018

Schnitzler syndrome co-occurring with idiopathic multicentric Castleman disease that responds to anti-IL-1 therapy: A case report and clue to pathophysiology.

Curr Res Transl Med 2018 09 11;66(3):83-86. Epub 2018 Aug 11.

CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.

Patients with HHV-8-negative/idiopathic multicentric Castleman disease (iMCD) experience systemic inflammatory symptoms and polyclonal lymphoproliferation due to an unknown etiology. Schnitzler's syndrome (SS) is characterized by recurrent urticarial rash, monoclonal IgM gammopathy, and other clinical signs of inflammation. To our knowledge, we report the first case of iMCD associated with SS and the fourth case of anakinra inducing a complete response for an iMCD patient. A forty-four year old woman with a history of a recurrent urticarial rash, presented to our hospital complaining of 6 months of night sweats, fever, chronic urticaria, iliac bone pain, and generalized lymphadenopathy. An IgM Kappa monoclonal component was measured at 7.8g/L. A lymph node biopsy revealed histopathological features consistent with the plasma cell variant of iMCD. She was diagnosed with SS and iMCD. Anti-IL-1 treatment with anakinra (100mg/day) was introduced. Within 48h, we observed improvement in the fever and the urticarial rash. By one month, we considered the patient in complete remission. Two years later, the remission is persistent while the patient is still under therapy. Though this is only the fourth reported case of anakinra in iMCD, this is yet another case demonstrating the effectiveness of anti-IL-1 blockade in SS. We hypothesize that uncontrolled cytokine production is responsible for both the SS and the iMCD. The etiologies of SS and iMCD are unknown, and future research is necessary.
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http://dx.doi.org/10.1016/j.retram.2018.06.001DOI Listing
September 2018