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低剂量 ATG 联合巴利昔单抗用于单倍体造血干细胞移植与有效控制 GVHD 和更少的 CMV 病毒血症相关。

Lower dose of ATG combined with basiliximab for haploidentical hematopoietic stem cell transplantation is associated with effective control of GVHD and less CMV viremia.

机构信息

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Immunol. 2022 Nov 15;13:1017850. doi: 10.3389/fimmu.2022.1017850. eCollection 2022.

Abstract

Currently, the graft-versus-host disease (GVHD) prophylaxis consists of an immunosuppressive therapy mainly based on antithymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). GVHD remains a major complication and limitation to successful allogeneic haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We modified the ATG-based GVHD prophylaxis with the addition of basiliximab in the setting of haplo-HSCT and attempted to explore the appropriate dosages. We conducted a retrospective analysis of 239 patients with intermediate- or high-risk hematologic malignancies who received haplo-HSCT with unmanipulated peripheral blood stem cells combined or not with bone marrow. All patients received the same GVHD prophylaxis consisting of the combination of methotrexate, cyclosporine or tacrolimus, mycofenolate-mofetil, and basiliximab with different doses of ATG (5-9mg/kg). With a median time of 11 days (range, 7-40 days), the rate of neutrophil engraftment was 96.65%. The 100-day cumulative incidences (CIs) of grade II-IV and III-IV aGVHD were 15.8 ± 2.5% and 5.0 ± 1.5%, while the 2-year CIs of total cGVHD and extensive cGVHD were 9.8 ± 2.2% and 4.1 ± 1.5%, respectively. The 3-year CIs of treatment-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) were 14.6 ± 2.6%, 28.1 ± 3.4%, 60.9 ± 3.4%, 57.3 ± 3.4%, respectively. Furthermore, the impact of the reduction of the ATG dose to 6 mg/kg or less in combination with basiliximab on GVHD prevention and transplant outcomes among patients was analyzed. Compared to higher dose of ATG(>6mg/kg), lower dose of ATG (≤6mg/kg) was associated with a significant reduced risk of CMV viremia (52.38% 79.35%, <0.001), while the incidences of aGVHD and cGVHD were similar between the two dose levels. No significant effect was found with regard to the risk of relapse, TRM, and OS. ATG combined with basiliximab could prevent GVHD efficiently and safely. The optimal scheme of using this combined regimen of ATG and basiliximab is that administration of lower dose ATG (≤6mg/kg), which seems to be more appropriate for balancing infection control and GVHD prophylaxis.

摘要

目前,移植物抗宿主病(GVHD)的预防包括主要基于抗胸腺细胞球蛋白(ATG)或移植后环磷酰胺(PTCy)的免疫抑制治疗。GVHD仍然是同种异体单倍体造血干细胞移植(haplo-HSCT)成功的主要并发症和限制因素。我们在 haplo-HSCT 中通过添加巴利昔单抗对基于 ATG 的 GVHD 预防进行了修改,并试图探索合适的剂量。我们对 239 例接受未经处理的外周血干细胞联合或不联合骨髓的 haplo-HSCT 的中高危血液系统恶性肿瘤患者进行了回顾性分析。所有患者均接受相同的 GVHD 预防方案,包括甲氨蝶呤、环孢素或他克莫司、霉酚酸酯和巴利昔单抗,并使用不同剂量的 ATG(5-9mg/kg)。中位时间为 11 天(范围为 7-40 天),中性粒细胞植入率为 96.65%。100 天的 II-IV 级和 III-IV 级急性移植物抗宿主病的累积发生率分别为 15.8%±2.5%和 5.0%±1.5%,而 2 年总慢性移植物抗宿主病和广泛慢性移植物抗宿主病的累积发生率分别为 9.8%±2.2%和 4.1%±1.5%。治疗相关死亡率(TRM)、复发、总生存(OS)和无病生存(DFS)的 3 年累积发生率分别为 14.6%±2.6%、28.1%±3.4%、60.9%±3.4%和 57.3%±3.4%。此外,还分析了降低 ATG 剂量至 6mg/kg 或以下联合巴利昔单抗对 GVHD 预防和移植结局的影响。与较高剂量的 ATG(>6mg/kg)相比,较低剂量的 ATG(≤6mg/kg)与 CMV 病毒血症的风险显著降低(52.38% vs 79.35%,<0.001)相关,而两组的急性移植物抗宿主病和慢性移植物抗宿主病发生率相似。在复发、TRM 和 OS 风险方面未发现显著影响。ATG 联合巴利昔单抗可有效、安全地预防 GVHD。使用 ATG 和巴利昔单抗联合方案的最佳方案是使用较低剂量的 ATG(≤6mg/kg),这似乎更适合于平衡感染控制和 GVHD 预防。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/9705727/4141ef328ec4/fimmu-13-1017850-g001.jpg

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