Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Hematology, Kanazawa University Hospital, Kanazawa, Japan.
Clin Cancer Res. 2020 Dec 15;26(24):6483-6493. doi: 10.1158/1078-0432.CCR-20-1104. Epub 2020 Sep 6.
Potent graft-versus-tumor (GVT) effects associated with graft-versus-host disease (GVHD) might be dependent on hematologic disease type and status. However, the data regarding the impact of GVHD on transplant outcomes for patients with myelodysplastic syndrome (MDS) are limited.
We retrospectively evaluated the impact of acute and chronic GVHD on transplant outcomes for a large cohort of adult patients with a low-risk ( = 1,193) and high-risk ( = 1,926) MDS treated by first allogeneic hematopoietic cell transplantation between 2001 and 2017.
The multivariate analysis, in which development of GVHD was treated as a time-dependent covariate, showed that acute and chronic GVHD at any grade or severity did not improve overall mortality, relapse, or nonrelapse mortality (NRM) in low-risk MDS. For patients with high-risk MDS, development of limited chronic GVHD was significantly associated with lower overall mortality [HR, 0.66; 95% confidence interval (CI), 0.50-0.86; = 0.002]. This is probably due to that the reduced risk of relapse with grade III-IV acute GVHD (HR, 0.41; 95% CI, 0.25-0.65; = 0.0002), or limited (HR, 0.57; 95% CI, 0.39-0.83; = 0.003) or extensive (HR, 0.56; 95% CI, 0.41-0.77; = 0.0004) chronic GVHD was offset by increased NRM with grade III-IV acute GVHD or extensive chronic GVHD in high-risk MDS.
These data demonstrated a survival benefit of the graft-versus-MDS effect is present only in high-risk MDS patients with limited chronic GVHD..
与移植物抗宿主病(GVHD)相关的强大移植物抗肿瘤(GVT)效应可能依赖于血液系统疾病的类型和状态。然而,关于 GVHD 对骨髓增生异常综合征(MDS)患者移植结局影响的数据有限。
我们回顾性评估了 2001 年至 2017 年间,接受首次异基因造血细胞移植的大量低危(n=1193)和高危(n=1926)MDS 成年患者中,急性和慢性 GVHD 对移植结局的影响。
多变量分析中,GVHD 的发生被视为一个时间依赖的协变量,结果显示,低危 MDS 患者中,任何级别或严重程度的急性和慢性 GVHD 均不能改善总死亡率、复发或非复发死亡率(NRM)。对于高危 MDS 患者,局限性慢性 GVHD 的发生与总死亡率降低显著相关[HR,0.66;95%置信区间(CI),0.50-0.86;P=0.002]。这可能是由于 3-4 级急性 GVHD 降低了复发风险(HR,0.41;95%CI,0.25-0.65;P=0.0002),或局限性(HR,0.57;95%CI,0.39-0.83;P=0.003)或广泛性(HR,0.56;95%CI,0.41-0.77;P=0.0004)慢性 GVHD 被 3-4 级急性 GVHD 或广泛性慢性 GVHD 导致的 NRM 增加所抵消。
这些数据表明,只有高危 MDS 患者发生局限性慢性 GVHD 时,才存在对 MDS 的移植物抗效应带来生存获益。