Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia.


Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
01 2020
Historique:
received: 27 04 2019
revised: 14 07 2019
accepted: 16 07 2019
pubmed: 5 8 2019
medline: 15 5 2021
entrez: 5 8 2019
Statut: ppublish

Résumé

Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients.

Sections du résumé

BACKGROUND
Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known.
OBJECTIVE
To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use.
METHODS
Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded.
RESULTS
We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID.
CONCLUSIONS
Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients.

Identifiants

pubmed: 31377437
pii: S2213-2198(19)30650-6
doi: 10.1016/j.jaip.2019.07.032
pii:
doi:

Substances chimiques

Rituximab 4F4X42SYQ6

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

273-282

Informations de copyright

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Auteurs

Giorgio Ottaviano (G)

Paediatric Haematology, Milano-Bicocca University, Monza, Italy. Electronic address: g.ottaviano2@campus.unimib.it.

Maddalena Marinoni (M)

Paediatric Department, ASST-Sette Laghi, "F. Del Ponte" Hospital, Varese, Italy.

Simona Graziani (S)

Paediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Roma Tor Vergata, Rome, Italy.

Keith Sibson (K)

Department of Haematology, Great Ormond Street Hospital, London, United Kingdom.

Federica Barzaghi (F)

Paediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Patrizia Bertolini (P)

Paediatric Hematology Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.

Loredana Chini (L)

Paediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Roma Tor Vergata, Rome, Italy.

Paola Corti (P)

Paediatric Haematology, Fondazione MBBM, Monza, Italy.

Caterina Cancrini (C)

University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Irene D'Alba (I)

Paediatric Haematology-Oncology, Maternal Infant Hospital "G. Salesi", Ancona, Italy.

Maria Gabelli (M)

Department of Women's and Children's Health, Pediatric Onco-Hematology Unit, University of Padova, Padova, Italy.

Vera Gallo (V)

Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy.

Carmela Giancotta (C)

University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Rome, Italy.

Paola Giordano (P)

Department of Biomedical Sciences and Human Oncology, University "A. Moro", Bari, Italy.

Giuseppe Lassandro (G)

Department of Biomedical Sciences and Human Oncology, University "A. Moro", Bari, Italy.

Baldassare Martire (B)

Paediatric Hematology Oncology Unit, "Policlinico-Giovanni XXII" Hospital, University of Bari, Bari, Italy.

Rosa Angarano (R)

Paediatric Hematology Oncology Unit, "Policlinico-Giovanni XXII" Hospital, University of Bari, Bari, Italy.

Elena Mastrodicasa (E)

Paediatric Onco-Haematology, Hospital of Perugia, Perugia, Italy.

Cecilia Bava (C)

Haematology Unit, IRCCS Istituto "G. Gaslini", Genova, Italy.

Maurizio Miano (M)

Haematology Unit, IRCCS Istituto "G. Gaslini", Genova, Italy.

Samuele Naviglio (S)

Pediatric Hematology-Oncology, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.

Federico Verzegnassi (F)

Pediatric Hematology-Oncology, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.

Paola Saracco (P)

Paediatric Haematology, Department of Paediatrics, University Hospital Città della Salute e della Scienza di Torino, Torino, Italy.

Antonino Trizzino (A)

Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina and Benfratelli Hospital, Palermo, Italy.

Andrea Biondi (A)

Paediatric Haematology, Milano-Bicocca University, Monza, Italy.

Claudio Pignata (C)

Department of Women's and Children's Health, Pediatric Onco-Hematology Unit, University of Padova, Padova, Italy.

Viviana Moschese (V)

Paediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Roma Tor Vergata, Rome, Italy.

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