HLA-mismatched transplants with either in vitro depletion of CD3 T-cell receptor (TCR)αβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using posttransplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEIs). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEIs undergoing their first transplant between 2010 and 2019 from an HLA-mismatched donor using TCRαβ (n = 167) or PTCY (n = 139). The median age for hematopoietic stem cell transplantation (HSCT) was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84) after TCRαβ and 66% (57-74) after PTCY ( = .013). Pre-HSCT morbidity score (hazard ratio [HR], 2.27; 1.07-4.80, = .032) and non-busulfan/treosulfan conditioning (HR, 3.12; 1.98-4.92, < .001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50%-66%) after TCRαβ and 57% (48%-66%) after PTCY ( = .804). The cumulative incidence of severe acute graft-versus-host disease (GvHD) was higher after PTCY (15%, 9%-21%) than TCRαβ (6%, 2%-9%, = .007), with no difference in chronic GvHD (PTCY, 11%, 6%-17%; TCRαβ, 7%, 3%-11%, = .173). The 3-year GvHD-free EFS was 53% (44%-61%) after TCRαβ and 41% (32%-50%) after PTCY ( = .080). PTCY had significantly higher rates of veno-occlusive disease (14.4% vs TCRαβ 4.9%, = .009), acute kidney injury (12.7% vs 4.6%, = .032), and pulmonary complications (38.2% vs 24.1%, = .017). Adenoviremia (18.3% vs PTCY 8.0%, = .015), primary graft failure (10% vs 5%, = .048), and second HSCT (17.4% vs 7.9%, = .023) were significantly higher in TCRαβ. In conclusion, this study demonstrates that both approaches are suitable options in patients with IEIs, although they are characterized by different advantages and outcomes.

中文翻译：

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HLA 不匹配 HSCT 联合 TCRαβ/CD19 去除或 HSCT 后环磷酰胺治疗先天性免疫缺陷的结果

HLA 不匹配的移植物通过体外去除 CD3 T 细胞受体 (TCR)αβ/CD19 (TCRαβ) 细胞或使用移植后环磷酰胺 (PTCY) 进行体内 T 细胞去除已越来越多地用于患有先天性免疫缺陷的患者。 IEI）。我们通过 EBMT 注册中心对 306 名 IEI 儿童进行了一项回顾性多中心研究，这些儿童在 2010 年至 2019 年间接受了 HLA 不匹配供体的首次移植，使用 TCRαβ (n = 167) 或 PTCY (n = 139)。造血干细胞移植（HSCT）的中位年龄为1.2岁（范围0.03-19.6岁）。 TCRαβ 后 3 年总生存率 (OS) 为 78%（95% 置信区间 (CI)，71-84），PTCY 后为 66%（57-74）（= .013）。 HSCT 前发病率评分（风险比 [HR]，2.27；1.07-4.80，= .032）和非白消安/三硫丹调理（HR，3.12；1.98-4.92，< .001）是不利 OS 的唯一独立预测因素。 TCRαβ 后的 3 年无事件生存率 (EFS) 为 58% (50%-66%)，PTCY 后为 57% (48%-66%) (= .804)。 PCY 后严重急性移植物抗宿主病 (GvHD) 的累积发生率 (15%, 9%-21%) 高于 TCRαβ (6%, 2%-9%, = .007)，但在慢性 GvHD（PTCY，11%、6%-17%；TCRαβ，7%、3%-11%，= .173）。 TCRαβ 后 3 年无 GvHD EFS 为 53% (44%-61%)，PTCY 后为 41% (32%-50%) (= .080)。 PTCY 的静脉闭塞性疾病（14.4% vs TCRαβ 4.9%，= .009）、急性肾损伤（12.7% vs 4.6%，= .032）和肺部并发症（38.2% vs 24.1%，= .032）的发生率显着较高。 017）。 TCRαβ 中的腺病毒血症（18.3% vs PTCY 8.0%，= .015）、原发性移植失败（10% vs 5%，= .048）和第二次 HSCT（17.4% vs 7.9%，= .023）显着较高。总之，本研究表明，这两种方法都是 IEI 患者的合适选择，尽管它们具有不同的优点和结果。