Romain Levy1, Matthieu Mahévas2, Lionel Galicier3, David Boutboul3, Julien Moroch4, Valentine Loustau1, Constance Guillaud1, Laeticia Languille1, Olivier Fain5, Philippe Bierling1, Medhi Khellaf1, Marc Michel1, Eric Oksenhendler3, Bertrand Godeau1. 1. Service de Médecine Interne, Centre de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France. 2. Service de Médecine Interne, Centre de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France; Etablissement Français du Sang Ile de France, Inserm U955, Equipe 2, Créteil, Hôpital Henri Mondor, Paris, France. Electronic address: matthieu.mahevas@hmn.aphp.fr. 3. Service d'Immunologie Clinique, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Université Paris Diderot Paris VII, Paris, France. 4. Service d'Anatomie et Cytologie Pathologiques, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France. 5. Service de Médecine Interne, Hôpital Jean-Verdier, Assistance Publique-Hôpitaux de Paris, Université Paris XIII, Bondy, France.
Abstract
INTRODUCTION: B-cell depletion with rituximab (RTX) is widely used to treat autoimmune diseases, especially as second-line therapy for immune thrombocytopenia (ITP). The incidence of RTX-induced hypogammaglobulinemia is unknown because of heterogeneous follow-up and confounding factors such as concomitant immunosuppressive treatments in most patients. We describe 3 cases and attempted to determine the incidence of RTX-induced hypogammaglobulinemia by a systematic review of the literature. METHODS: We retrospectively analyzed 189 ITP patients receiving RTX in 3 referral centers in France and conducted a systematic review of 32 studies (results published 2001-2014) reporting the use of RTX for ITP, particularly searching for symptomatic secondary hypogammaglobulinemia. We also searched for case reports of hypogammaglobulinemia after RTX initiation for ITP. RESULTS: Of the 189 patients, 3 showed symptomatic hypogammaglobulinemia more than 2years after RTX infusion (initial immunoglobulin level was normal). All 3 presented recurrent severe infections. In 2, the outcome suggested common variable immunodeficiency. In patient 3, the peripheral blood lacked CD19(+)CD20(+) B cells and the bone-marrow B-cell precursor level was impaired. Among 1245 ITP patients in the literature who received RTX for ITP, gammaglobulin level was monitored before and after RTX initiation for 351 (28%). For 192 (55%), dosages were available and we identified 21 patients with secondary hypogammaglobulinemia, usually not symptomatic, 14 of whom had received concomitant dexamethasone. Finally, we found 4 case reports of ITP and symptomatic hypogammaglobulinemia possibly related to RTX according to the authors. CONCLUSIONS: This large analysis led us to recommend monitoring serum immunoglobulin level before and repeatedly after RTX initiation for ITP. Physicians should be aware of hypogammaglobulinemia as a rare but severe complication of RTX.
INTRODUCTION: B-cell depletion with rituximab (RTX) is widely used to treat autoimmune diseases, especially as second-line therapy for immune thrombocytopenia (ITP). The incidence of RTX-induced hypogammaglobulinemia is unknown because of heterogeneous follow-up and confounding factors such as concomitant immunosuppressive treatments in most patients. We describe 3 cases and attempted to determine the incidence of RTX-induced hypogammaglobulinemia by a systematic review of the literature. METHODS: We retrospectively analyzed 189 ITP patients receiving RTX in 3 referral centers in France and conducted a systematic review of 32 studies (results published 2001-2014) reporting the use of RTX for ITP, particularly searching for symptomatic secondary hypogammaglobulinemia. We also searched for case reports of hypogammaglobulinemia after RTX initiation for ITP. RESULTS: Of the 189 patients, 3 showed symptomatic hypogammaglobulinemia more than 2years after RTX infusion (initial immunoglobulin level was normal). All 3 presented recurrent severe infections. In 2, the outcome suggested common variable immunodeficiency. In patient 3, the peripheral blood lacked CD19(+)CD20(+) B cells and the bone-marrow B-cell precursor level was impaired. Among 1245 ITP patients in the literature who received RTX for ITP, gammaglobulin level was monitored before and after RTX initiation for 351 (28%). For 192 (55%), dosages were available and we identified 21 patients with secondary hypogammaglobulinemia, usually not symptomatic, 14 of whom had received concomitant dexamethasone. Finally, we found 4 case reports of ITP and symptomatic hypogammaglobulinemia possibly related to RTX according to the authors. CONCLUSIONS: This large analysis led us to recommend monitoring serum immunoglobulin level before and repeatedly after RTX initiation for ITP. Physicians should be aware of hypogammaglobulinemia as a rare but severe complication of RTX.
Authors: Emilie Reboursiere; H Fouques; G Maigne; H Johnson; S Chantepie; A C Gac; O Reman; M Macro; K Benabed; X Troussard; G Damaj; S Cheze Journal: Int J Hematol Date: 2016-04-04 Impact factor: 2.490
Authors: Tanaya Shree; Qian Li; Sally L Glaser; Ann Brunson; Holden T Maecker; Robert W Haile; Ronald Levy; Theresa H M Keegan Journal: J Clin Oncol Date: 2020-02-21 Impact factor: 50.717