title: Characteristics, outcome, and response to therapy of multirefractory chronic immune thrombocytopenia.
abstract: Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio [OR], 4.84; 95% confidence interval [CI], 1.31-17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease.
authors.affiliation: Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France;
authors.forename: Matthieu
authors.initials: M
authors.lastname: Mahévas
authors.affiliation: Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France; Service de Médecine Interne, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Université Claude Bernard, Lyon, France;
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gerfaud-Valentin
authors.affiliation: Service de Médecine Interne, Centre Hospitalier Universitaire (CHU) de Toulouse, Toulouse, France; Unité Mixte de Recherche (UMR) 1027 INSERM-Université de Toulouse, Toulouse, France; Centre d'investigation Clinique 1436, CHU de Toulouse, Toulouse, France;
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moulis
authors.affiliation: Service de Médecine Interne et Immunologie Clinique, Hôpital Claude-Huriez, Centre Hospitalier Régional Universitaire de Lille, Université Lille Nord de France, Lille, France;
authors.forename: Louis
authors.initials: L
authors.lastname: Terriou
authors.affiliation: Service de Médecine Interne et Immunologie Clinique, Centre de Compétences des Cytopénies Auto-immunes de l'adulte, Hôpital Bocage Central, CR INSERM 1098, Dijon, France;
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.affiliation: Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France;
authors.forename: Sophie
authors.initials: S
authors.lastname: Guenin
authors.affiliation: Service de Médecine Interne, Hôpital Estaing, CHU de Clermont-Ferrand, Clermont-Ferrand, France;
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Guenno
authors.affiliation: Service d'Hématologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Université Claude Bernard, UMR Centre National de la Recherche (CNRS)5239, Pierre-Bénite, France;
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: AP-HP, Service de Médecine Interne-Immunologie Clinique, Hôpitaux Universitaires Paris Sud, Université Paris Sud, le Kremlin Bicêtre, France; UMR 1184, Commissariat à l'Énergie Atomique (CEA), Institut des Maladies Émergentes et des Thérapies Innovantes (DSV/iMETI), Division of Immuno-Virology, IDMIT, le Kremlin Bicêtre, France; INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, le Kremlin Bicêtre, France;
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Limal
authors.affiliation: Service de Médecine Interne et Maladies Infectieuses, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France;
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Viallard
authors.affiliation: Service d'Hématologie Clinique, CHU Côte de Nacre, Caen, France;
authors.forename: Stephane
authors.initials: S
authors.lastname: Cheze
authors.affiliation: Service d'Hématologie, CHU de Poitiers, Poitiers, France;
authors.forename: Cecile
authors.initials: C
authors.lastname: Tomowiak
authors.affiliation: Service d'Hématologie Clinique et Thérapie Cellulaire, CHU d'Amiens, Hôpital Sud, Amiens, France;
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.affiliation: Service de Médecine Interne, CHU de Nantes, Nantes, France;
authors.forename: Antoine
authors.initials: A
authors.lastname: Neel
authors.affiliation: Service de Médecine Interne, CHU de Poitiers, Poitiers, France;
authors.forename: Odile
authors.initials: O
authors.lastname: Debouverie
authors.affiliation: Service de Médecine Interne, Hospices Civils de Lyon, Hôpital Edouard Herriot, Université Claude Bernard, Lyon, France;
authors.forename: Arnaud
authors.initials: A
authors.lastname: Hot
authors.affiliation: Service de Médecine Interne, Hospices Civils de Lyon, Hôpital Lyon Sud, Université Claude Bernard, Pierre-Bénite, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durieu
authors.affiliation: Pôle Accueil Urgences, Médecine Interne-Gériatrie, Service de Médecine Interne, Hôpital Sud, CHU de Rennes, Rennes, France;
authors.forename: Antoinette
authors.initials: A
authors.lastname: Perlat
authors.affiliation: Service d'Onco-Hématologie, Groupe Hospitalier de l'Institut Catholique de Lille, Hôpital Saint Vincent de Paul, Lille, France; and.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cliquennois
authors.affiliation: Service d'Hématologie, Clinique Universitaire d'Hématologie, CHU Grenoble, UMR 5525 CNRS-Université Joseph Fourier (UJF), Grenoble, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Deteix
authors.affiliation: Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France;
authors.forename: Marc
authors.initials: M
authors.lastname: Michel
authors.affiliation: Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France;
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godeau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000628:therapy*; D011961:Receptors, Fc / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use*; D013156:Splenectomy / Q000009:adverse effects*; D015996:Survival Rate; D013926:Thrombopoietin / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D000069283:Rituximab; D013926:Thrombopoietin; C488777:romiplostim