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.
Blood. 2017 Apr 13;129(15):2198-2201. doi: 10.1182/blood-2016-11-748616. Epub 2017 Feb 16.
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 (, .06). B-lymphocyte and myeloid chimerism were highly correlated (ρ, 0.98; < .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.
造血干细胞移植（HSCT）可治愈白细胞介素 2 γ 链受体（IL2RG）/JAK3 严重联合免疫缺陷（SCID）患者的 T 淋巴细胞、B 淋巴细胞和自然杀伤（NK）细胞分化缺陷。我们评估了我们中心 >2 年 HSCT 后 IL2RG/JAK3 SCID 患者的长期临床特征、纵向免疫重建、供体嵌合状态和生活质量（QoL）。我们整理了临床数据，并让患者/家属回答了 PedsQL 通用核心量表 v4.0 问卷。我们对移植前至移植后 15 年期间 CD3、CD4 幼稚 T 淋巴细胞、CD19 和 NK 细胞数量进行了纵向分析。43 例患者中有 31 例（72%）存活。最后一次随访时的中位年龄为 10 岁（范围，2-25 岁）。21 例（68%）存在持续性医疗问题，主要是持续免疫球蛋白替代治疗（14 例；45%）、皮肤病毒性疣（7 例；24%）、身材矮小（4 例；14%）、四肢淋巴水肿（3 例；10%）和支气管扩张（2 例；7%）。有 6 例患者提供了肺功能数据，结果均正常。纵向分析表明，HSCT 后 15 年仍能持续产生 CD3、CD19 和 NK 细胞。经预处理和未经预处理的受者 CD4 幼稚淋巴细胞数量更好（，.06）。B 淋巴细胞和髓样嵌合状态高度相关（ρ，0.98； <.001）。低毒性清髓性预处理受者具有更好的 B 淋巴细胞/髓样嵌合状态，并且无需免疫球蛋白替代治疗。无需免疫球蛋白替代治疗的 IL2RG/JAK3 SCID 幸存者生活质量正常。
