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Abstract：
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.
摘要：
我们在急性白血病和骨髓增生异常综合征（MDS）儿童中进行了T细胞受体αβ（TCR-αβ）/CD19耗尽的单倍体相合造血细胞移植（HCT）的前瞻性多中心研究，确定1年无病生存期（DFS），并与其他供体细胞来源的接受者比较2年结局。招募了51名年龄在0.7至21岁之间的患者；基于配体错配和/或高B含量，供体为杀手免疫球蛋白样受体（KIR）。1年DFS为78％。在<10岁的患者中发现了2年DFS和总生存期（OS）。那些用减毒调理（RTC）而不是清髓性调理治疗的患者，HCT前微小残留病<0.01％的儿童。将KIR有利的单倍体队列与对照进行比较的多变量分析显示，与其他供体细胞来源相比，DFS和OS相似。多变量分析还显示，2至4级和3至4级急性移植物抗宿主病（aGVHD）的风险显着降低，慢性GVHD,和移植相关的死亡率与其他供体细胞来源。少数民族和少数民族占登记患者的53%，来自接受KIR筛查的大量受者/捐献者的数据显示，根据我们的定义，>80%的受者有KIR有利的捐献者，证明这种方法广泛适用于通常无法找到捐助者的群体。这个未来,多中心研究显示，使用TCR-αβ/CD19耗尽的单倍体供体，使用RTC治疗急性白血病和MDS儿童的结局有所改善。将这种方法与匹配的无关供体进行比较的随机试验是必要的。该试验在https://clinicaltrials.gov上注册为#NCT02646839。
