Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignancies. Twenty NBS patients received 22 allogeneic HSCTs with TCRαβ/CD19+ graft depletion with fludarabine 150 mg/m², cyclophosphamide 20–40 mg/kg and thymoglobulin 5 mg/kg based conditioning regimens (CRs). Twelve patients additionally received low-dose busulfan 4 mg/kg (Bu group) and 10 patients (including 2 recipients of a second HSCT) treosulfan (Treo group) 30 g/m². Overall and event-free survival were 0.75 vs 1 (p = 0.16) and 0.47 vs 0.89 (p = 0.1) in the Bu and Treo groups, respectively. In the Bu group, four patients developed graft rejection, and three died: two died of de novo and relapsed lymphomas and one died of adenoviral hepatitis. The four living patients exhibited split chimerism with predominantly recipient myeloid cells and predominantly donor T and B lymphocytes. In Treo group, one patient developed rhabdomyosarcoma. There was no difference in the incidence of GVHD, viral reactivation, or early toxicity between either group. Low-dose Bu-containing CR in NBS leads to increased graft failure and low donor myeloid chimerism. Treo-CR followed by TCRαβ/CD19-depleted HSCT demonstrates a low level of early transplant-associated toxicity and enhanced graft function with stable donor chimerism.

奈梅亨断裂综合征 (NBS) 是一种 DNA 修复障碍，其特征是联合免疫缺陷和高度易患恶性肿瘤。HSCT 似乎可以治愈免疫缺陷，但由于在移植相关毒性和恶性肿瘤的长期风险方面经验有限，因此仍然具有挑战性。20 名 NBS 患者接受了 22 次异基因 HSCT，其中 TCRαβ/CD19+ 移植物耗竭，氟达拉滨 150 mg/m ²、环磷酰胺 20–40 mg/kg 和胸腺球蛋白 5 mg/kg 基于预处理方案 (CRs)。12 名患者另外接受了低剂量白消安 4 mg/kg（Bu 组）和 10 名患者（包括第二次 HSCT 的 2 名接受者）硫丹（Treo 组）30 g/m ²。总体生存率和无事件生存率分别为 0.75 vs 1 ( p =  0.16) 和 0.47 vs 0.89 ( p = 0.1) 分别在 Bu 和 Treo 组中。Bu组4例患者出现移植排斥反应，3例死亡：2例死于新发和复发性淋巴瘤，1例死于腺病毒性肝炎。四名活着的患者表现出分裂嵌合现象，主要是受体骨髓细胞，主要是供体 T 和 B 淋巴细胞。在 Treo 组中，一名患者出现了横纹肌肉瘤。两组之间 GVHD、病毒再激活或早​​期毒性的发生率没有差异。NBS 中的低剂量含 Bu CR 导致移植失败增加和低供体髓系嵌合现象。Treo-CR 和 TCRαβ/CD19 耗尽的 HSCT 显示出低水平的早期移植相关毒性和增强的移植物功能，具有稳定的供体嵌合体。