Sistema de Salut de Catalunya
Institut Català de la Salut
[Lankester AC, von Asmuth EGJ] Pediatric Stem Cell Transplantation Program and Laboratory for Pediatric Immunology, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands. [Neven B] Unité d’Immuno-hematologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. Université de Paris, Paris, France. Institut Imagine, INSERM UMR1163, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Paris, France. [Mahlaoui N, Courteille V, Alligon M] French National Reference Center for Primary Immunodeficiencies (CEREDIH) and European Registry for Stem Cell Transplantation for Primary Immunodeficiencies (SCETIDE), Hôpital Universitaire Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. [Diaz-de-Heredia C] Servei d’Oncologia i Hematologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2022-07-19T08:40:42Z
2022-07-19T08:40:42Z
2022-05-01
Genetic subgroups; Immune reconstitution; Pretransplantation infections
Subgrupos genéticos; Reconstitución inmune; Infecciones previas al trasplante
Subgrups genètics; Reconstitució immune; Infeccions prèvies al trasplantament
Background Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome. Objective We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome. Methods HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed. Results Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P < .001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P < .001). Genetic subgroups did not differ in 2-year OS (P = .1) and EFS (P = .073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor–deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5 × 10e3/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome. Conclusion Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.
Article
Published version
English
Malalties congènites; Cèl·lules mare hematopoètiques - Trasplantació; DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Infant, Newborn, Diseases::Severe Combined Immunodeficiency; Other subheadings::Other subheadings::Other subheadings::/genetics; ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades del recién nacido::inmunodeficiencia combinada grave; Otros calificadores::Otros calificadores::Otros calificadores::/genética
Elsevier
Journal of Allergy and Clinical Immunology;149(5)
https://doi.org/10.1016/j.jaci.2021.10.017
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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