We performed a prospective multicenter study of T-cell receptor αβ (TCR-αβ)/CD19-depleted haploidentical hematopoietic cell transplantation (HCT) in children with acute leukemia and myelodysplastic syndrome (MDS), to determine 1-year disease-free survival (DFS) and compare 2-year outcomes with recipients of other donor cell sources. Fifty-one patients aged 0.7 to 21 years were enrolled; donors were killer immunoglobulin-like receptor (KIR) favorable based on ligand mismatch and/or high B content. The 1-year DFS was 78%. Superior 2-year DFS and overall survival (OS) were noted in patients <10 years of age, those treated with reduced toxicity conditioning (RTC) rather than myeloablative conditioning, and children with minimal residual disease <0.01% before HCT. Multivariate analysis comparing the KIR-favorable haploidentical cohort with controls showed similar DFS and OS compared with other donor cell sources. Multivariate analysis also showed a marked decrease in the risk of grades 2 to 4 and 3 to 4 acute graft versus host disease (aGVHD), chronic GVHD, and transplant-related mortality vs other donor cell sources. Ethnic and racial minorities accounted for 53% of enrolled patients, and data from a large cohort of recipients/donors screened for KIR showed that >80% of recipients had a KIR-favorable donor by our definition, demonstrating that this approach is broadly applicable to groups often unable to find donors. This prospective, multicenter study showed improved outcomes using TCR-αβ/CD19-depleted haploidentical donors using RTC for children with acute leukemia and MDS. Randomized trials comparing this approach with matched unrelated donors are warranted. This trial was registered at https://clinicaltrials.gov as #NCT02646839.

中文翻译：

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ALL/AML/MDS 儿童中 KIR 有利的 TCR-αβ/CD19 耗尽单倍相合 HCT：PTCTC ONC1401 试验的初步分析。


我们对患有急性白血病和骨髓增生异常综合征 (MDS) 的儿童进行了 T 细胞受体 αβ (TCR-αβ)/CD19 耗尽的半相合造血细胞移植 (HCT) 的前瞻性多中心研究，以确定 1 年无病生存率。 DFS）并与其他供体细胞来源的受者比较 2 年结果。纳入 51 名年龄在 0.7 至 21 岁之间的患者；基于配体不匹配和/或高B含量，供体对杀伤性免疫球蛋白样受体（KIR）有利。 1 年 DFS 为 78%。根据我们的定义，<10 id=32>80% 的受者拥有 KIR 有利的供体，这表明该方法广泛适用于经常无法找到供体的群体。这项前瞻性、多中心研究表明，使用 RTC 治疗急性白血病和 MDS 儿童，使用 TCR-αβ/CD19 耗尽的半相合供体可改善预后。有必要进行随机试验，将这种方法与匹配的无关捐赠者进行比较。该试验在 https://clinicaltrials.gov 上注册为#NCT02646839。