Division of Hematology and Oncology, Intermountain Primary Children's Hospital, Huntsman Cancer Institute at the University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT.
Section of Transplantation and Cellular Therapy, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA.
Blood. 2022 Dec 15;140(24):2556-2572. doi: 10.1182/blood.2022015959.
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.
我们进行了一项前瞻性、多中心研究，旨在评估 T 细胞受体 αβ（TCR-αβ）/CD19 耗竭的单倍体相合造血细胞移植（HCT）在儿童急性白血病和骨髓增生异常综合征（MDS）中的疗效，以确定 1 年无病生存（DFS）率，并与其他供者来源的受者进行 2 年结局比较。共纳入 51 例年龄 0.7 至 21 岁的患者；供者根据配体错配和/或高 B 含量，具有杀伤免疫球蛋白样受体（KIR）有利型。1 年 DFS 率为 78%。年龄<10 岁、接受低强度预处理（RTC）而非清髓性预处理、HCT 前微小残留病<0.01%的患者，2 年DFS 和总生存（OS）更优。将 KIR 有利型单倍体相合组与对照组进行多变量分析，结果显示与其他供者来源相比，DFS 和 OS 相似。多变量分析还显示，与其他供者来源相比，2 级至 4 级和 3 级至 4 级急性移植物抗宿主病（aGVHD）、慢性 GVHD 和移植相关死亡率的风险显著降低。入组患者中少数民族占 53%，对大量受者/供者进行 KIR 筛查的数据显示，>80%的受者按我们的定义具有 KIR 有利型供者，表明该方法广泛适用于通常难以找到供者的人群。这项前瞻性、多中心研究显示，采用 RTC 并用 TCR-αβ/CD19 耗竭的单倍体相合供者治疗儿童急性白血病和 MDS 可改善结局。有必要开展比较这种方法与匹配的无关供者的随机试验。该试验在 https://clinicaltrials.gov 注册，编号为 #NCT02646839。
