Background

Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants.

Objective

We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD-causing T-cell receptor (TCR) αβ CD3⁺ cells from the graft.

Methods

CD3⁺TCRαβ⁺/CD19⁺ depleted grafts were given in conditioned (except 3) children with PIDs. Treosulfan (busulfan in 1 patient), fludarabine, thiotepa, and anti-thymocyte globulin or alemtuzumab conditioning were used in 77% of cases, and all but 4 received GvHD prophylaxis.

Results

Twenty-five patients with 12 types of PIDs received 26 HSCTs. Three underwent transplantation for refractory GvHD that developed after the first cord transplantation. At a median follow-up of 20.8 months (range, 5 month-3.3 years), 21 of 25 patients survived and were cured of underlying immunodeficiency. Overall and event-free survival at 3 years were 83.9% and 80.4%, respectively. Cumulative incidence of grade II to IV acute GvHD was 22% ± 8.7%. No case of visceral or chronic GvHD was seen. Cumulative incidences of graft failure, cytomegalovirus, and/or adenoviral infections and transplant-related mortality at 1 year were 4.2% ± 4.1%, 58.8% ± 9.8%, and 16.1% ± 7.4%, respectively. Patients undergoing transplantation with systemic viral infections had poor survival in comparison with those with absent or resolved infections (33.3% vs 100%).

Conclusion

CD3⁺TCRαβ⁺ and CD19⁺ cell–depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.

中文翻译：

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T 细胞受体 αβ+ 和 CD19+ 细胞耗竭的单倍体相合和错配的造血干细胞移植治疗原发性免疫缺陷

背景

异基因造血干细胞移植 (HSCT) 被用作原发性免疫缺陷 (PID) 的治疗方法。使用 HLA 匹配的供体取得了最好的结果，但是当匹配的供体不可用时，单倍体相合或不匹配的无关供体 (mMUD) 可能有用。各种策略用于降低移植物抗宿主病 (GvHD) 和与此类移植相关的排斥反应的风险。

客观的

我们试图在从移植物中耗尽引起 GvHD 的 T 细胞受体 (TCR) αβ CD3 ⁺细胞后评估半相合或 mMUD HSCT 的结果。

方法

CD3 ⁺ TCRαβ ⁺ /CD19 ⁺耗尽的移植物被给予患有 PID 的条件性（3 名除外）儿童。77% 的病例使用了 Treosulfan（1 例患者使用白消安）、氟达拉滨、噻替哌和抗胸腺细胞球蛋白或阿仑单抗预处理，除 4 例外，所有病例均接受了 GvHD 预防。

结果

25 名 12 种 PID 患者接受了 26 次 HSCT。三人接受了第一次脐带移植后出现的难治性 GvHD 移植。在 20.8 个月（范围，5 个月至 3.3 年）的中位随访中，25 名患者中有 21 名存活并治愈了潜在的免疫缺陷。3 年总生存率和无事件生存率分别为 83.9% 和 80.4%。II 至 IV 级急性 GvHD 的累积发生率为 22% ± 8.7%。没有发现内脏或慢性 GvHD 病例。移植失败、巨细胞病毒和/或腺病毒感染的累积发生率和移植相关死亡率在 1 年内分别为 4.2% ± 4.1%、58.8% ± 9.8% 和 16.1% ± 7.4%。与没有感染或感染消失的患者相比，接受移植的全身病毒感染患者的生存率较差（33.3% vs 100%）。

结论

CD3 ⁺ TCRαβ ⁺和 CD19 ⁺细胞耗尽的单倍体或 mMUD HSCT 对于患有一系列 PID 的儿童来说是一种实用且可行的替代方案。