Kiumarsi Azadeh, Alaei Amirarsalan, Nikbakht Mohsen, Mohammadi Saeed, Ostad-Ali Mohammad Reza, Rasti Zahra, Rostami Tahereh
Department of Pediatrics, School of Medicine, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Front Immunol. 2025 Jan 8;15:1475448. doi: 10.3389/fimmu.2024.1475448. eCollection 2024.
With recent advances in clinical practice, including the use of reduced-toxicity conditioning regimens and innovative approaches such as ex vivo TCRαβ/CD19 depletion of haploidentical donor stem cells or post-transplant cyclophosphamide (PTCY), hematopoietic stem cell transplantation (HSCT) has emerged as a curative treatment option for a growing population of patients with inborn errors of immunity (IEI). However, despite these promising developments, graft failure (GF) remains a significant concern associated with HSCT in these patients. Although a second HSCT is the only established salvage therapy for patients who experience GF, there are no uniform, standardized strategies for performing these second transplants. Furthermore, even less data is available regarding the outcomes and best practices for a third HSCT as a salvage measure when a second HSCT fails to achieve engraftment.
A 6-year-old boy with leukocyte adhesion deficiency type I (LAD-I) experienced GF after the first and second HSCT from a matched unrelated donor. As a salvage measure, the patient received a dual T-cell depleted haploidentical HSCT. The conditioning regimen for this third HSCT included anti-thymocyte globulin (ATG) and PTCY. Complete donor chimerism was assessed using the short tandem repeat (STR) PCR technique. By day +28 after the transplant, the expression of the leukocyte adhesion molecules CD18, CD11b, and CD11c on the patient's peripheral blood neutrophils had recovered to over 99%. It remained stable throughout the 18-month follow-up period.
T-cell replete haploidentical HSCT with ATG and PTCY may be a viable salvage option for LAD patients who have rejected prior HSCT.
随着临床实践的最新进展，包括使用低毒性预处理方案以及创新方法，如对单倍体相合供体干细胞进行体外TCRαβ/CD19去除或移植后环磷酰胺（PTCY），造血干细胞移植（HSCT）已成为越来越多先天性免疫缺陷（IEI）患者的一种治愈性治疗选择。然而，尽管有这些令人鼓舞的进展，但移植物失败（GF）仍然是这些患者HSCT相关的一个重大问题。虽然二次HSCT是经历GF的患者唯一既定的挽救治疗方法，但对于进行这些二次移植并没有统一、标准化的策略。此外，当二次HSCT未能实现植入时，作为挽救措施的第三次HSCT的结果和最佳实践的数据甚至更少。
一名患有I型白细胞黏附缺陷（LAD-I）的6岁男孩在接受来自匹配无关供体的第一次和第二次HSCT后发生了GF。作为挽救措施，该患者接受了双T细胞去除的单倍体相合HSCT。第三次HSCT的预处理方案包括抗胸腺细胞球蛋白（ATG）和PTCY。使用短串联重复序列（STR）PCR技术评估完全供体嵌合状态。移植后第28天，患者外周血中性粒细胞上白细胞黏附分子CD18、CD11b和CD11c的表达恢复到99%以上。在整个18个月的随访期内保持稳定。
对于先前HSCT失败的LAD患者，采用ATG和PTCY的T细胞充足的单倍体相合HSCT可能是一种可行的挽救选择。
