Department of Pediatric Hematology/Oncology & Bone Marrow Transplantation Unit, Acıbadem University, Istanbul, Turkey.
Acibadem Labcell Cellular Therapy Laboratory, Istanbul, Turkey.
Pediatr Transplant. 2021 Dec;25(8):e14120. doi: 10.1111/petr.14120. Epub 2021 Aug 19.
Haploidentical HSCT is a good option for children with PIDs lacking an HLA-matched donor. Co-transplantation of MSCs during haploidentical HSCT in patients with PIDs may enhance engraftment, decrease the risk of GVHD, and ensure stable donor chimerism.
Twenty-seven pediatric patients (median age, 1.4 years; range, .3-10.9) with PIDs undergoing thirty haploidentical HSCT with TCR αβ depletion and co-transplantation of MSCs were enrolled to study. Most patients (73.3%) received myeloablative conditioning consisting of treosulfan or busulfan, fludarabine, and thiotepa. The median duration of follow-up was 14.3 months (range, 1-69 months).
Acute GVHD occurred in 7 patients (grade I-II n = 5, grade III-IV n = 2). Chronic GVHD was observed in only one patient. Twenty-one patients (70.2%) had 100% donor chimerism in all cell lines including T-cell and B-cell lineages. Primary graft failure was observed in 7 patients (25.9%). The cumulative incidences of TRM were 20% at day 100, and 26.7% at one year and five years. Probabilities of OS were 80% at day 100, and 71.9% at 1 year and 5 years. Infants transplanted younger than 6 months of age had the highest 5-year survival rate (85.7%).
We conclude that use of TCR αβ depleted haploidentical transplantation with MSCs may ensure a rapid engraftment rate, low incidence of significant acute and chronic GVHD, and acceptable post-transplantation morbidity, especially in patients diagnosed with SCID and may be considered in children with PIDs. In younger patients (≤6 months), survival is comparable between HLA-matched graft and CD3+ TCRαβ depleted HLA-mismatched graft recipients.
对于缺乏 HLA 匹配供体的 PID 患儿，单倍体 HSCT 是一种很好的选择。在 PID 患者的单倍体 HSCT 中同时移植 MSC 可能会增强植入，降低 GVHD 的风险，并确保稳定的供体嵌合状态。
本研究纳入了 27 例接受 TCRαβ 耗竭的单倍体 HSCT 联合 MSC 移植的 PID 患儿（中位年龄 1.4 岁，范围 0.3-10.9 岁）。大多数患者（73.3%）接受了包含噻替哌、白消安或硼替佐米、氟达拉滨的清髓性预处理方案。中位随访时间为 14.3 个月（范围 1-69 个月）。
7 例（1-2 级 n=5，3-4 级 n=2）患儿发生急性 GVHD，仅 1 例患儿发生慢性 GVHD。21 例（70.2%）患儿在 T 细胞和 B 细胞谱系中所有细胞系均达到 100%供者嵌合。7 例（25.9%）患儿发生原发性移植物失败。100 天时 TRM 的累积发生率为 20%，1 年和 5 年时分别为 26.7%。100 天时 OS 率为 80%，1 年和 5 年时分别为 71.9%。6 个月以下婴儿的 5 年生存率最高（85.7%）。
我们认为使用 TCRαβ 耗竭的单倍体移植联合 MSC 可确保快速植入率、急性和慢性 GVHD 发生率低，且移植后发病率可接受，特别是在 SCID 患儿中，在 PID 患儿中也可考虑使用。在年龄较小的患者（≤6 个月）中，HLA 匹配和 CD3+TCRαβ 耗竭 HLA 不匹配移植受者的生存率相当。
