Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA-matched stem-cell transplantation for acute myeloid leukemia.

IF 12.8 1区 医学 Q1 HEMATOLOGY
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
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引用次数: 0

Abstract

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.

移植后环磷酰胺可分离 HLA 匹配干细胞移植治疗急性髓性白血病后的移植物抗宿主病和移植物抗白血病效应。
异基因干细胞移植(SCT)后的移植物抗宿主病(GVHD)和移植物抗白血病(GVL)效应之间的关联已得到证实,但在现代和移植后环磷酰胺(PTCy)治疗中尚未得到证实。我们评估了HLA配型相合的SCT后AML患者的GVHD/GVL相关性,这些患者接受了基于标准钙调素的GVHD预防(n = 12,653,57%的患者接受了额外的体内T细胞耗竭)或基于PTCy的GVHD预防(n = 508)。标准预防后,II-IV级和III-IV级急性GVHD、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%。II级和III-IV级急性GVHD与较低的复发率[危险比(HR)分别为0.85,P = 0.002;HR 0.76,P = 0.003]、较高的非复发死亡率(NRM)(HR 1.5,P
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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