Clinical, immunological and psycho-social outcome of SCID patients who underwent hematopoietic stem cell transplantation in Newcastle, UK, 1987-2012 and long-term outcome of the UK SCID cohort

Abstract

Background - Severe Combined Immunodeficiencies (SCID) are primary immunodeficiencies with defective development and/or/function of T-lymphocyte, B-lymphocyte and Natural Killer cells. Hematopoietic stem cell transplantation (HSCT) corrects immunodeficiency but long-term impact of pre-HSCT chemotherapy, and immunoreconstitution are poorly documented. We explored: clinical outcome, immunoreconstitution, and quality of life (QoL) in SCID survivors >2 years post-HSCT (Newcastle cohort), newborn SCID (Newcastle cohort) and >20 years post-HSCT (Newcastle and London cohort). Methods A retrospective longitudinal study of long-term outcome of post-HSCT SCID patients by genotype (Newcastle), newborn diagnosis of SCID and >20 years long-term outcome of UK SCID HSCT patients. Clinico-immunological data from London and Newcastle were retrospectively collated. Patients and families attending the Newcastle HSCT follow-up clinic were invited to complete PedsQL questionnaires. Descriptive analyses were performed for clinical outcome. Longitudinal analyses assessed immunoreconstitution changes post-HSCT. Health-related questionnaire results were compared to UK norms. Results - 102 patients were identified from Newcastle with 49 patients were diagnosed during neonatal period and 74 patients for the UK study of >20 years post-HSCT long-term outcome. Many patients have on-going medical issues at latest follow-up [IL2RG/JAK3 (68%), IL7Rα (73%), Artemis (85%), RAG 1/2 (55%) and ADA SCID (87%)]. Some issues were genotype-specific; papillomata in IL2RG/JAK3/IL7Rα SCID, neurocognitive issues and hearing loss in ADA SCID. Artemis SCID patients experienced more sequalae than RAG 1/2 SCID. Conditioned recipients with IL2RG/JAK3 SCID, ADA, Artemis and RAG SCID had more CD4+ naïve lymphocytes compared to unconditioned recipients. B-lymphocyte chimerism mirrored myeloid chimerism and those with more than 50% donor chimerism were more likely to be immunoglobulin independent. All parents except those of IL7Rα SCID reported lower QoL; further subset group analysis showed parents and IL2RG/JAK3 SCID immunoglobulin-independent survivors plus Artemis/RAG1/2 survivors without on-going medical issues reported normal QoL. Both parents and ADA SCID survivors reported lower QoL. Conclusions - Conditioned recipients have superior long-term thymopoiesis, chimerism and immunoglobulin-independence. Quality of life was normal in those who were immunoglobulin-independent or normal health.