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Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA-matched stem-cell transplantation for acute myeloid leukemia
Leukemia ( IF 12.8 ) Pub Date : 2024-10-31 , DOI: 10.1038/s41375-024-02445-x
Avichai Shimoni, Christophe Peczynski, Myriam Labopin, Alexander Kulagin, Ellen Meijer, Jan Cornelissen, Goda Choi, Jaime Sanz, Montserrat Rovira, Gwendolyn Van Gorkom, Nicolaus Kröger, Yener Koc, Jan Vydra, J. L. Diez-Martin, Carlos Solano, Amit Patel, Patrizia Chiusolo, Fabio Ciceri, Arnon Nagler, Mohamad Mohty

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.



中文翻译:


移植后环磷酰胺可区分急性髓性白血病 HLA 匹配干细胞移植后移植物抗宿主病和移植物抗白血病效应



同种异体干细胞移植 (SCT) 后移植物抗宿主病 (GVHD) 和移植物抗白血病 (GVL) 效应的关联已得到明确,但在现代和移植后环磷酰胺 (PTCy) 之后尚未得到证实。我们评估了 HLA 匹配 SCT 与基于标准钙调神经磷酸酶 (n = 12,653, 57% 有额外的体内 T 细胞耗竭) 或基于 PTCy (n = 508) GVHD 预防后 AML 患者的 GVHD/GVL 关联。标准预防后,急性 GVHD II-IV 级和 III-IV 级、慢性 GVHD 和广泛慢性 GVHD 的发生率分别为 23.8% 、 7.5% 、 37.0% 和 16.3%。急性 GVHD II 级和 III-IV 级与较低的复发率相关 [风险比 (HR) 0.85,P = 0.002; HR 0.76,分别为 P = 0.003)],较高的非复发死亡率 (NRM) (HR 1.5,P < 0.001;HR 6.21,P < 0.001)和较低的总生存期 (OS) (HR 1.49,P < 0.001; HR 6.1,P < 0.001)。 广泛性慢性 GVHD 预测复发率较低 (HR 0.69,P < 0.001),NRM 较高 (HR 2.83,P < 0.001) 和较低 OS (HR 2.74,P < 0.001)。PTCy 后,GVHD 发生率分别为 22.8% 、 6.2% 、 35.5% 和 17.7%。急性 GVHD 与复发无关 (HR 1.37,P = 0.15),但预测 NRM 较高 (HR 3.34,P < 0.001) 和较低 OS (HR 1.92,P = 0.001)。 慢性 GVHD 对这些结局没有预后影响。总之,GVHD 和 GVL 与当代 SCT 密切相关。然而,在 PTCy 之后,GVHD 与复发率降低无关。

更新日期:2024-11-01
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