title: Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report.
abstract: Hematopoietic stem cell transplantation (HSCT) cures the T-lymphocyte, B-lymphocyte, and natural killer (NK)-cell differentiation defect in interleukin-2 γ-chain receptor (IL2RG)/JAK3 severe combined immunodeficiency (SCID). We evaluated long-term clinical features, longitudinal immunoreconstitution, donor chimerism, and quality of life (QoL) of IL2RG/JAK3 SCID patients >2 years post-HSCT at our center. Clinical data were collated and patients/families answered PedsQL Generic Core Scale v4.0 questionnaires. We performed longitudinal analyses of CD3+, CD4+naive T-lymphocyte, CD19+, and NK-cell numbers from pretransplant until 15 years posttransplant. Thirty-one of 43 patients (72%) survived. Median age at last follow-up was 10 years (range, 2-25 years). Twenty-one (68%) had persistent medical issues, mainly ongoing immunoglobulin replacement (14; 45%), cutaneous viral warts (7; 24%), short stature (4; 14%), limb lymphoedema (3; 10%), and bronchiectasis (2; 7%). Lung function was available and normal for 6 patients. Longitudinal analysis demonstrated sustained CD3+, CD19+, and NK-cell output 15 years post-HSCT. CD4+naive lymphocyte numbers were better in conditioned vs unconditioned recipients (P, .06). B-lymphocyte and myeloid chimerism were highly correlated (ρ, 0.98;P< .001). Low-toxicity myeloablative conditioning recipients have better B-lymphocyte/myeloid chimerism and are free from immunoglobulin replacement therapy. IL2RG/JAK3 SCID survivors free from immunoglobulin replacement have normal QoL.
authors.affiliation: Pediatric Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.|Department of Paediatric Immunology and Hematopoietic Stem Cell Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.|Regenerative Medicine Cluster, Institut Perubatan and Pergigian Termaju, Universiti Sains Malaysia, Kepala Batas, Malaysia.
authors.forename: Intan Juliana
authors.identifier: 0000-0001-6749-1498
authors.initials: IJ
authors.lastname: Abd Hamid
authors.affiliation: Pediatric Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.|Department of Paediatric Immunology and Hematopoietic Stem Cell Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Slatter
authors.affiliation: Department of Health Psychology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; and.
authors.forename: Fiona
authors.initials: F
authors.lastname: McKendrick
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Pearce
authors.affiliation: Pediatric Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.|Department of Paediatric Immunology and Hematopoietic Stem Cell Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D053616:Janus Kinase 3; D008297:Male; D011788:Quality of Life; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; C507933:JAK3 protein, human; D053616:Janus Kinase 3