Giorgio Ottaviano1, Maddalena Marinoni2, Simona Graziani3, Keith Sibson4, Federica Barzaghi5, Patrizia Bertolini6, Loredana Chini3, Paola Corti7, Caterina Cancrini8, Irene D'Alba9, Maria Gabelli10, Vera Gallo11, Carmela Giancotta12, Paola Giordano13, Giuseppe Lassandro13, Baldassare Martire14, Rosa Angarano14, Elena Mastrodicasa15, Cecilia Bava16, Maurizio Miano16, Samuele Naviglio17, Federico Verzegnassi17, Paola Saracco18, Antonino Trizzino19, Andrea Biondi20, Claudio Pignata10, Viviana Moschese3. 1. Paediatric Haematology, Milano-Bicocca University, Monza, Italy. Electronic address: g.ottaviano2@campus.unimib.it. 2. Paediatric Department, ASST-Sette Laghi, "F. Del Ponte" Hospital, Varese, Italy. 3. Paediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Roma Tor Vergata, Rome, Italy. 4. Department of Haematology, Great Ormond Street Hospital, London, United Kingdom. 5. Paediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. 6. Paediatric Hematology Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 7. Paediatric Haematology, Fondazione MBBM, Monza, Italy. 8. 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. 9. Paediatric Haematology-Oncology, Maternal Infant Hospital "G. Salesi", Ancona, Italy. 10. Department of Women's and Children's Health, Pediatric Onco-Hematology Unit, University of Padova, Padova, Italy. 11. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. 12. University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Rome, Italy. 13. Department of Biomedical Sciences and Human Oncology, University "A. Moro", Bari, Italy. 14. Paediatric Hematology Oncology Unit, "Policlinico-Giovanni XXII" Hospital, University of Bari, Bari, Italy. 15. Paediatric Onco-Haematology, Hospital of Perugia, Perugia, Italy. 16. Haematology Unit, IRCCS Istituto "G. Gaslini", Genova, Italy. 17. Pediatric Hematology-Oncology, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy. 18. Paediatric Haematology, Department of Paediatrics, University Hospital Città della Salute e della Scienza di Torino, Torino, Italy. 19. Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina and Benfratelli Hospital, Palermo, Italy. 20. Paediatric Haematology, Milano-Bicocca University, Monza, Italy.
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.
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.
Authors: Stephen L Hauser; Anne H Cross; Kevin Winthrop; Heinz Wiendl; Jacqueline Nicholas; Sven G Meuth; Paul S Giacomini; Francesco Saccà; Linda Mancione; Ronald Zielman; Morten Bagger; Ayan Das Gupta; Dieter A Häring; Valentine Jehl; Bernd C Kieseier; Ratnakar Pingili; Dee Stoneman; Wendy Su; Roman Willi; Ludwig Kappos Journal: Mult Scler Date: 2022-03-01 Impact factor: 5.855