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.
Hematopoietic stem cell transplantation (HSCT) is curative for severe combined immunodeficiency (SCID), but data on long-term impact of pre-HSCT chemotherapy, immune reconstitution and quality of life (QoL) of specific SCID genotypes are limited. We evaluated the long-term immune-reconstitution, health outcome and QoL in IL7Rα SCID, Artemis and RAG1 and 2 SCID survivors > 2 years post-HSCT in our center. Clinical data and immune reconstitution parameters were collated, and patients/families answered PedsQL generic core scale v4.0 questionnaires. Thirty-nine patients with a diagnosis of IL7Rα SCID (17 patients), Artemis SCID (8 patients) and RAG1/2 SCID (13 patients) had undergone HSCT with median age at last follow up for IL7Rα SCID, 14 years (range 4-27) and Artemis and RAG1/2 SCID, 10 years (range 2-18). Many patients have ongoing medical issues at latest follow-up [IL7Rα (73%), Artemis (85%), RAG1/2 (55%)]. Artemis SCID patients experienced more sequela than RAG1/2 SCID. Conditioned recipients with Artemis and RAG SCID had more CD4+ naïve lymphocytes compared to unconditioned recipients. All patients except those of IL7Rα SCID reported lower QoL; further subset group analysis showed parents and Artemis and RAG1/2 survivors without ongoing medical issues reported normal QoL. Conditioned recipients have superior long-term thymopoiesis, chimerism and immunoglobulin-independence. QoL was normal in those who did not have medical issues at long-term follow-up.