Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

Giorgio Ottaviano, Maddalena Marinoni, Simona Graziani, Keith Sibson, Federica Barzaghi, Patrizia Bertolini, Loredana Chini, Paola Corti, Caterina Cancrini, Irene D'Alba, Maria Gabelli, Vera Gallo, Carmela Giancotta, Paola Giordano, Giuseppe Lassandro, Baldassare Martire, Rosa Angarano, Elena Mastrodicasa, Cecilia Bava, Maurizio MianoSamuele Naviglio, Federico Verzegnassi, Paola Saracco, Antonino Trizzino, Andrea Biondi, Claudio Pignata, Viviana Moschese

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology: In Practice
DOIs
Publication statusE-pub ahead of print - Aug 2 2019

Fingerprint

Agammaglobulinemia
Autoimmune Hemolytic Anemia
Idiopathic Thrombocytopenic Purpura
B-Lymphocytes
IgA Deficiency
Lymphopenia
Rituximab
Immunoglobulin M
Immunoglobulin G
Evans Syndrome

Cite this

Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia. / Ottaviano, Giorgio; Marinoni, Maddalena; Graziani, Simona; Sibson, Keith; Barzaghi, Federica; Bertolini, Patrizia; Chini, Loredana; Corti, Paola; Cancrini, Caterina; D'Alba, Irene; Gabelli, Maria; Gallo, Vera; Giancotta, Carmela; Giordano, Paola; Lassandro, Giuseppe; Martire, Baldassare; Angarano, Rosa; Mastrodicasa, Elena; Bava, Cecilia; Miano, Maurizio; Naviglio, Samuele; Verzegnassi, Federico; Saracco, Paola; Trizzino, Antonino; Biondi, Andrea; Pignata, Claudio; Moschese, Viviana.

In: Journal of Allergy and Clinical Immunology: In Practice, 02.08.2019.

Research output: Contribution to journalArticle

Ottaviano, G, Marinoni, M, Graziani, S, Sibson, K, Barzaghi, F, Bertolini, P, Chini, L, Corti, P, Cancrini, C, D'Alba, I, Gabelli, M, Gallo, V, Giancotta, C, Giordano, P, Lassandro, G, Martire, B, Angarano, R, Mastrodicasa, E, Bava, C, Miano, M, Naviglio, S, Verzegnassi, F, Saracco, P, Trizzino, A, Biondi, A, Pignata, C & Moschese, V 2019, 'Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia', Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2019.07.032
Ottaviano, Giorgio ; Marinoni, Maddalena ; Graziani, Simona ; Sibson, Keith ; Barzaghi, Federica ; Bertolini, Patrizia ; Chini, Loredana ; Corti, Paola ; Cancrini, Caterina ; D'Alba, Irene ; Gabelli, Maria ; Gallo, Vera ; Giancotta, Carmela ; Giordano, Paola ; Lassandro, Giuseppe ; Martire, Baldassare ; Angarano, Rosa ; Mastrodicasa, Elena ; Bava, Cecilia ; Miano, Maurizio ; Naviglio, Samuele ; Verzegnassi, Federico ; Saracco, Paola ; Trizzino, Antonino ; Biondi, Andrea ; Pignata, Claudio ; Moschese, Viviana. / Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia. In: Journal of Allergy and Clinical Immunology: In Practice. 2019.
@article{e87ec5c7bb34406b87e88aa85e2371d6,
title = "Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia",
abstract = "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.",
author = "Giorgio Ottaviano and Maddalena Marinoni and Simona Graziani and Keith Sibson and Federica Barzaghi and Patrizia Bertolini and Loredana Chini and Paola Corti and Caterina Cancrini and Irene D'Alba and Maria Gabelli and Vera Gallo and Carmela Giancotta and Paola Giordano and Giuseppe Lassandro and Baldassare Martire and Rosa Angarano and Elena Mastrodicasa and Cecilia Bava and Maurizio Miano and Samuele Naviglio and Federico Verzegnassi and Paola Saracco and Antonino Trizzino and Andrea Biondi and Claudio Pignata and Viviana Moschese",
note = "Copyright {\circledC} 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "8",
day = "2",
doi = "10.1016/j.jaip.2019.07.032",
language = "English",
journal = "Journal of Allergy and Clinical Immunology: In Practice",
issn = "2213-2198",
publisher = "American Academy of Allergy, Asthma and Immunology",

}

TY - JOUR

T1 - Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

AU - Ottaviano, Giorgio

AU - Marinoni, Maddalena

AU - Graziani, Simona

AU - Sibson, Keith

AU - Barzaghi, Federica

AU - Bertolini, Patrizia

AU - Chini, Loredana

AU - Corti, Paola

AU - Cancrini, Caterina

AU - D'Alba, Irene

AU - Gabelli, Maria

AU - Gallo, Vera

AU - Giancotta, Carmela

AU - Giordano, Paola

AU - Lassandro, Giuseppe

AU - Martire, Baldassare

AU - Angarano, Rosa

AU - Mastrodicasa, Elena

AU - Bava, Cecilia

AU - Miano, Maurizio

AU - Naviglio, Samuele

AU - Verzegnassi, Federico

AU - Saracco, Paola

AU - Trizzino, Antonino

AU - Biondi, Andrea

AU - Pignata, Claudio

AU - Moschese, Viviana

N1 - Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

PY - 2019/8/2

Y1 - 2019/8/2

N2 - 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.

AB - 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.

U2 - 10.1016/j.jaip.2019.07.032

DO - 10.1016/j.jaip.2019.07.032

M3 - Article

C2 - 31377437

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

SN - 2213-2198

ER -