Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Department of Hospital Pharmacy, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
J Clin Immunol. 2021 Jul;41(5):944-957. doi: 10.1007/s10875-021-00966-z. Epub 2021 Feb 1.
The purpose of our study was to compare the safety and efficacy of hematopoietic cell transplantation (HCT) using fludarabine (Flu)-based reduced intensity conditioning (RIC) with busulfan (BU) or melphalan (Mel) for primary immunodeficiency diseases (PID).
We retrospectively analyzed transplant outcome, including engraftment, chimerism, immune reconstitution, and complications in 15 patients with severe combined immunodeficiency (SCID) and 27 patients with non-SCID PID. The patients underwent Flu-based RIC-HCT with BU (FluBU: 7 SCID, 16 non-SCID) or Mel (FluMel: 8 SCID, 11 non-SCID). The targeted low-dose BU with therapeutic drug monitoring was set to 30 mg hour/L for SCID.
The 2-year overall survival of all patients was 79.6% and that of patients with SCID in the FluBU and FluMel groups was 100% and 62.5%, respectively. In the FluBU group, all seven patients achieved engraftment, good immune reconstitution, and long-term survival. All five patients receiving umbilical cord blood transplantation achieved complete or high-level mixed chimerism and sufficient specific IgG production. In the FluMel group, six of eight patients achieved complete or high-level mixed chimerism. Viral reactivation or new viral infection occurred in one FluBU group patient and four FluMel group patients. In the non-SCID group, 10 of 11 patients (91%) who received FluMel achieved complete or high-level mixed chimerism but had variable outcomes. Patients with WAS (2/2 patients), NEMO deficiency (2/2 patients), and X-linked hyper IgM syndrome (2/3 patients) who received FluBU achieved complete or high-level mixed chimerism and long-term survival.
RIC-HCT with FluBU is a safe and effective strategy for obtaining high-level donor chimerism, immune reconstitution including B cell function, and long-term survival in patients with SCID. In patients with non-SCID PID, the results varied according to the subtype of the disease. Further prospective studies are required to optimize the conditioning regimen for non-SCID PID.
本研究旨在比较氟达拉滨（Flu）为基础的降低强度预处理（RIC）联合白消安（BU）或马利兰（Mel）用于原发性免疫缺陷病（PID）的造血细胞移植（HCT）的安全性和有效性。
我们回顾性分析了 15 例严重联合免疫缺陷（SCID）和 27 例非-SCID PID 患者的移植结果，包括植入、嵌合体、免疫重建和并发症。患者接受 Flu 为基础的 RIC-HCT 联合 BU（FluBU：7 例 SCID，16 例非-SCID）或 Mel（FluMel：8 例 SCID，11 例非-SCID）。通过治疗药物监测将靶向低剂量 BU 设置为 30mg·h/L，用于 SCID。
所有患者的 2 年总生存率为 79.6%，FluBU 和 FluMel 组的 SCID 患者分别为 100%和 62.5%。在 FluBU 组中，7 例患者均实现了植入、良好的免疫重建和长期生存。所有接受脐带血移植的 5 例患者均实现了完全或高水平混合嵌合体和足够的特异性 IgG 产生。在 FluMel 组中，8 例患者中的 6 例实现了完全或高水平混合嵌合体。1 例 FluBU 组患者和 4 例 FluMel 组患者发生病毒再激活或新的病毒感染。在非-SCID 组中，11 例患者中有 10 例（91%）接受 FluMel 治疗后实现了完全或高水平混合嵌合体，但结果各异。接受 FluBU 治疗的 WAS（2/2 例）、NEMO 缺陷（2/2 例）和 X 连锁高 IgM 综合征（2/3 例）患者均实现了完全或高水平混合嵌合体和长期生存。
FluBU 联合 RIC-HCT 是一种安全有效的策略，可以获得高水平的供体嵌合体、包括 B 细胞功能的免疫重建和 SCID 患者的长期生存。在非-SCID PID 患者中，根据疾病的亚型，结果各不相同。需要进一步的前瞻性研究来优化非-SCID PID 的预处理方案。
