Background

Currently, there are no approved therapies to treat congenital athymia, a condition of immune deficiency resulting in high early mortality due to infection and immune dysregulation. Multiple syndromic conditions, such as complete DiGeorge syndrome, 22q11.2 deletion syndrome, CHARGE (coloboma, heart defects, choanal atresia, growth or mental retardation, genital hypoplasia, and ear anomalies and/or deafness) syndrome, diabetic embryopathy, other genetic variants, and FOXN1 deficiency, are associated with congenital athymia.

Objective

Our aims were to study 105 patients treated with cultured thymus tissue (CTT), and in this report, to focus on the outcomes of 95 patients with treatment-naive congenital athymia.

Methods

A total of 10 prospective, single-arm open-label studies with patient enrollment from 1993 to 2020 form the basis of this data set. Patients were tested after administration of CTT for T-cell development; all adverse events and infections were recorded.

Results

A total of 105 patients were enrolled and received CTT (the full analysis set). Of those patients, 10 had diagnoses other than congenital athymia and/or received prior treatments. Of those 105 patients, 95 patients with treatment-naive congenital athymia were included in the efficacy analysis set (EAS). The Kaplan-Meier estimated survival rates at year 1 and year 2 after administration of CTT in the EAS were 77% (95% CI = 0.670-0.844) and 76% (95% CI = 0.657-0.834), respectively. In all, 21 patients died in the first year before developing naive T cells and 1 died in the second year after receipt of CTT; 3 subsequent deaths were not related to immunodeficiency. A few patients developed alopecia, autoimmune hepatitis, psoriasis, and psoriatic arthritis after year 1. The rates of infections, autologous graft-versus-host-disease manifestations, and autoimmune cytopenias all decreased approximately 1 year after administration of CTT.

Conclusion

Treatment with CTT led to development of naive T cells with a 1-year survival rate of 77% and a median follow-up time of 7.6 years. Immune reconstitution sufficient to prevent infections and support survival typically develops 6 to12 months after administration of CTT.

中文翻译：

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105名儿童胸腺组织培养经验

背景

目前，没有批准的疗法来治疗先天性无胸腺症，这是一种免疫缺陷病，由于感染和免疫失调导致早期死亡率很高。多种综合征，例如完全 DiGeorge 综合征、22q11.2 缺失综合征、CHARGE（缺损、心脏缺陷、后鼻孔闭锁、生长或智力迟钝、生殖器发育不全、耳部异常和/或耳聋）综合征、糖尿病胚胎病、其他遗传变异和 FOXN1 缺乏症与先天性无胸腺症有关。

客观的

我们的目的是研究 105 名接受培养胸腺组织 (CTT) 治疗的患者，在本报告中，重点关注 95 名初治先天性无胸腺患者的结局。

方法

从 1993 年到 2020 年，共有 10 项前瞻性、单臂开放标签研究构成了该数据集的基础。给予 CTT 后对患者进行 T 细胞发育测试；记录所有不良事件和感染。

结果

共有 105 名患者入组并接受了 CTT（完整分析集）。在这些患者中，有 10 人被诊断为先天性无胸腺症和/或接受过先前的治疗。在这 105 名患者中，95 名初治先天性无胸腺症患者被纳入疗效分析集 (EAS)。Kaplan-Meier 估计在 EAS 中使用 CTT 后第 1 年和第 2 年的存活率分别为 77%（95% CI = 0.670-0.844）和 76%（95% CI = 0.657-0.834）。总共有 21 名患者在发育幼稚 T 细胞前的第一年死亡，1 名患者在接受 CTT 后的第二年死亡；随后的 3 例死亡与免疫缺陷无关。少数患者在 1 年后出现脱发、自身免疫性肝炎、银屑病和银屑病关节炎。感染率、自体移植物抗宿主病表现、

结论

用 CTT 治疗导致幼稚 T 细胞的发育，其 1 年存活率为 77%，中位随访时间为 7.6 年。足以预防感染和支持生存的免疫重建通常在 CTT 给药后 6 至 12 个月发生。