Molecular and Cellular Immunology Unit, University College London (UCL) Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Paediatric Allergy and Immunology, Ain Shams University, Cairo, Egypt.
Blood and Bone Marrow Transplant Unit, Great Ormond Street Hospital, London, United Kingdom; Department of Paediatric Oncology and BMT, Alberta Children's Hospital, Calgary, Alberta, Canada.
J Allergy Clin Immunol. 2019 Jul;144(1):280-293. doi: 10.1016/j.jaci.2019.01.030. Epub 2019 Feb 4.
Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks.
We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies.
Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched grafts: 30 T-cell receptor (TCR) αβ/CD19-depleted grafts, 43 cord blood (CB) grafts (72% with no serotherapy), 17 CD34 selection with T-cell add-back grafts, and 65 unmanipulated grafts.
The estimated 8-year survival of the entire cohort was 79%, transplant-related mortality was 21.7%, and the graft failure rate was 6.7%. Posttransplantation viral reactivation, grade II to IV acute graft-versus-host disease (aGvHD), and chronic graft-versus-host disease (cGvHD) complicated 49.6%, 35%, and 15% of transplantations, respectively. Use of TCRαβ/CD19 depletion was associated with a significantly lower incidence of grade II to IV aGvHD (11.5%) and cGvHD (0%), although with a greater incidence of viral reactivation (70%) in comparison with other grafts. T-cell immune reconstitution was robust among CB transplants, although with a high incidence (56.7%) of grade II to IV aGvHD. Stable full donor engraftment was significantly greater at 80% among TCRαβ/CD19-depleted and CB transplants versus 40% to 60% among the other groups.
Rapidly accessible CB and haploidentical grafts are suitable alternatives for patients with no HLA-matched donor. Cord transplantation without serotherapy and TCRαβ/CD19-depleted grafts produced comparable survival rates of around 80%, although with a high rate of aGvHD with the former and a high risk of viral reactivation with the latter that need to be addressed.
不合型干细胞移植与移植物丢失、移植物抗宿主病（GvHD）和移植相关死亡率高相关。在过去的 11 年中，已经使用了替代的移植物处理策略来降低这些风险。
我们研究了在原发性免疫缺陷儿童中使用不同移植物处理策略的结果。
在 2006 年至 2017 年间，147 名原发性免疫缺陷患者接受了 155 个不合型移植物：30 个 TCRαβ/CD19 耗竭移植物、43 个脐带血（CB）移植物（72%无血清治疗）、17 个 CD34 选择加 T 细胞回输移植物和 65 个未处理的移植物。
整个队列的 8 年估计生存率为 79%，移植相关死亡率为 21.7%，移植物失败率为 6.7%。移植后病毒再激活、II 至 IV 级急性移植物抗宿主病（aGvHD）和慢性移植物抗宿主病（cGvHD）的发生率分别为 49.6%、35%和 15%。与其他移植物相比，TCRαβ/CD19 耗竭的使用与 II 至 IV 级 aGvHD（11.5%）和 cGvHD（0%）的发生率显著降低相关，但病毒再激活的发生率较高（70%）。CB 移植中 T 细胞免疫重建较为活跃，尽管 II 至 IV 级 aGvHD 的发生率较高（56.7%）。TCRαβ/CD19 耗竭和 CB 移植的稳定完全供者嵌合率明显高于其他组的 40%至 60%。
快速获得的 CB 和半相合移植物是没有 HLA 匹配供体患者的合适选择。无血清治疗的 CB 移植和 TCRαβ/CD19 耗竭移植物产生了类似的 80%左右的生存率，尽管前者的 aGvHD 发生率较高，后者的病毒再激活风险较高，需要加以解决。
