INTRODUCTION The live-attenuated BCG vaccine is known to cause disseminated Mycobacterium bovis infection in patients with severe combined immunodeficiency (SCID). However, BCG-related post-hematopoietic stem cell transplantation (HSCT) immune reconstitution inflammatory syndromes, similar to those described in patients with HIV infections, are less-known complications of SCID. PATIENTS AND METHODS We reported on 22 BCG-vaccinated SCID patients who had received conditioned allogeneic HSCT with TCRαβ+/CD19+ graft depletion. All BCG-vaccinated patients received anti-mycobacterial therapy pre- and post-HSCT. Post-transplant immunosuppression consisted of tacrolimus in 10 patients and of 8 mg/kg tocilizumab (d-1, + 14, + 28) and 10 mg/kg abatacept (d-1, + 5, + 14, + 28) in 11 patients. RESULTS Twelve patients, five of whom had BCG infection prior to HSCT, developed BCG-related inflammatory syndromes (BCG-IS). Five developed early BCG-IS with the median time of manifestation 11 days after HSCT, corresponding with a dramatic increase of CD3+TCRγδ+ in at least two patients. Early BCG-IS was noted in only one out of 11 patients who received tocilizumab/abatacept and 4 out of 11 patients who did not. Seven patients developed late BCG-IS which corresponded to T cell immune recovery; at the time of manifestation (median 4.2 months after HSCT), the median number of CD3+ cells was 0.42 × 109/ and CD3+CD4+ cells 0.27 × 109/l. In all patients, late BCG-IS was controlled with IL-1 or IL-6 inhibitors. CONCLUSION BCG-vaccinated SCID patients undergoing allogeneic HSCT with TCRαβ+/CD19+ graft depletion are at an increased risk of early and late BCG-IS. Anti-inflammatory therapy with IL-1 and IL-6 blockade is efficient in the prevention of early and treatment of late BCG-IS.

中文翻译：

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TCRαβ+/CD19+ 耗竭造血干细胞移植后严重联合免疫缺陷患者的 BCG 相关炎症综合征。

引言 已知 BCG 减毒活疫苗会在严重联合免疫缺陷 (SCID) 患者中引起播散性牛分枝杆菌感染。然而，BCG 相关的造血后干细胞移植 (HSCT) 免疫重建炎症综合征，类似于 HIV 感染患者中描述的那些，是 SCID 鲜为人知的并发症。患者和方法 我们报告了 22 名接受 BCG 疫苗接种的 SCID 患者，这些患者接受了 TCRαβ+/CD19+ 移植物耗竭的条件性同种异体造血干细胞移植。所有接种 BCG 疫苗的患者在造血干细胞移植前后都接受了抗分枝杆菌治疗。移植后免疫抑制包括 10 名患者使用他克莫司，11 名患者使用 8 mg/kg 托珠单抗 (d-1, + 14, + 28) 和 10 mg/kg 阿巴西普 (d-1, + 5, + 14, + 28)耐心。结果 12 名患者，其中 5 人在 HSCT 之前曾感染 BCG，并发展为 BCG 相关炎症综合征 (BCG-IS)。5 人发展为早期 BCG-IS，中位时间在 HSCT 后 11 天，相应地至少有 2 名患者 CD3+TCRγδ+ 显着增加。接受托珠单抗/阿巴西普治疗的 11 名患者中只有 1 名出现早期 BCG-IS，未接受托珠单抗/阿巴西普治疗的 11 名患者中有 4 名出现早期 BCG-IS。7 名患者出现晚期 BCG-IS，这与 T 细胞免疫恢复相对应；在表现时（HSCT 后中位数 4.2 个月），CD3+ 细胞的中位数为 0.42 × 109/l，CD3+CD4+ 细胞数为 0.27 × 109/l。在所有患者中，晚期 BCG-IS 被 IL-1 或 IL-6 抑制剂控制。结论 接受 BCG 疫苗接种的 SCID 患者接受同种异体造血干细胞移植且 TCRαβ+/CD19+ 移植物耗竭，早期和晚期 BCG-IS 的风险增加。