Outcome of autoimmune cytopenia after hematopoietic cell transplantation in primary immunodeficiency.
Antibodies, Monoclonal, Humanized
/ therapeutic use
B-Lymphocytes
/ immunology
Child
Combined Modality Therapy
Female
Graft vs Host Disease
/ epidemiology
Hematopoietic Stem Cell Transplantation
Humans
Immunologic Factors
/ therapeutic use
Incidence
Male
Postoperative Complications
/ epidemiology
Primary Immunodeficiency Diseases
/ therapy
Retrospective Studies
Rituximab
/ therapeutic use
Sirolimus
/ therapeutic use
Transplantation Conditioning
Treatment Outcome
United Kingdom
/ epidemiology
pediatrics
posttransplant autoimmune cytopenia
primary immunodeficiency
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
06
10
2019
revised:
02
04
2020
accepted:
09
04
2020
pubmed:
23
5
2020
medline:
6
3
2021
entrez:
23
5
2020
Statut:
ppublish
Résumé
Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potentially life-threatening complication, but studies focusing on large cohorts of patients transplanted for primary immunodeficiency are lacking. This study sought to determine the incidence, risk factors, and outcomes of post-HCT AIC and B-lymphocyte function following rituximab. We retrospectively studied 502 children with primary immunodeficiency who were transplanted at our center between 1987 and 2018. Thirty-six patients (9%) developed post-HCT AIC, with a median onset of 6.5 months post-HCT. On univariate analysis, pre-HCT AIC, mismatched donor, alemtuzumab, anti-thymocyte antiglobulin, and acute and chronic graft versus host disease were significantly associated with post-HCT AIC. After multivariate analysis, alemtuzumab (subdistribution hazard ratio, 9.0; 95% CI, 1.50-54.0; P = .02) was independently associated with post-HCT AIC. Corticosteroid and high-dose intravenous immunoglobulin achieved remission in 50% (n = 18), additional rituximab led to remission in 25% (n = 9), and the remaining 25% were treated with a combination of various modalities including sirolimus (n = 5), bortezomib (n = 3), mycophenolate mofetil (n = 2), splenectomy (n = 2), and second HCT (n = 3). The mortality of post-HCT AIC reduced from 25% (4 of 16) prior to 2011 to 5% (1 of 20) after 2011. The median follow-up of 5.8 years (range, 0.4 to 29.1 years) showed that 26 of 30 survivors (87%) were in complete remission, and 4 were in remission with ongoing sirolimus and low-dose steroids. Of the 17 who received rituximab, 7 had B-lymphocyte recovery, 5 had persistent low B-lymphocyte count and remained on intravenous immunoglobulin replacement, 2 had second HCT, and 3 died. The frequency of post HCT AIC in our cohort was 9%, and the most significant risk factors for its occurrence were the presence of graft versus host disease and the use of alemtuzumab.
Sections du résumé
BACKGROUND
Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potentially life-threatening complication, but studies focusing on large cohorts of patients transplanted for primary immunodeficiency are lacking.
OBJECTIVES
This study sought to determine the incidence, risk factors, and outcomes of post-HCT AIC and B-lymphocyte function following rituximab.
METHODS
We retrospectively studied 502 children with primary immunodeficiency who were transplanted at our center between 1987 and 2018.
RESULTS
Thirty-six patients (9%) developed post-HCT AIC, with a median onset of 6.5 months post-HCT. On univariate analysis, pre-HCT AIC, mismatched donor, alemtuzumab, anti-thymocyte antiglobulin, and acute and chronic graft versus host disease were significantly associated with post-HCT AIC. After multivariate analysis, alemtuzumab (subdistribution hazard ratio, 9.0; 95% CI, 1.50-54.0; P = .02) was independently associated with post-HCT AIC. Corticosteroid and high-dose intravenous immunoglobulin achieved remission in 50% (n = 18), additional rituximab led to remission in 25% (n = 9), and the remaining 25% were treated with a combination of various modalities including sirolimus (n = 5), bortezomib (n = 3), mycophenolate mofetil (n = 2), splenectomy (n = 2), and second HCT (n = 3). The mortality of post-HCT AIC reduced from 25% (4 of 16) prior to 2011 to 5% (1 of 20) after 2011. The median follow-up of 5.8 years (range, 0.4 to 29.1 years) showed that 26 of 30 survivors (87%) were in complete remission, and 4 were in remission with ongoing sirolimus and low-dose steroids. Of the 17 who received rituximab, 7 had B-lymphocyte recovery, 5 had persistent low B-lymphocyte count and remained on intravenous immunoglobulin replacement, 2 had second HCT, and 3 died.
CONCLUSIONS
The frequency of post HCT AIC in our cohort was 9%, and the most significant risk factors for its occurrence were the presence of graft versus host disease and the use of alemtuzumab.
Identifiants
pubmed: 32442647
pii: S0091-6749(20)30682-5
doi: 10.1016/j.jaci.2020.04.053
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Immunologic Factors
0
tislelizumab
0KVO411B3N
Rituximab
4F4X42SYQ6
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
406-416Informations de copyright
Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.