Hematology Department, University Hospital of Salamanca, IBSAL Institute for Biomedical Research of Salamanca, Paseo de San Vicente, 139, 37007, Salamanca, Spain.
Department of Statistics, Faculty of Medicine, University of Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
Ann Hematol. 2019 Sep;98(9):2151-2162. doi: 10.1007/s00277-019-03751-6. Epub 2019 Jul 16.
Somatic mutations in patients with myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (HSTC) are associated with adverse outcome, but the role of chronic graft-versus-host disease (cGVHD) in this subset of patients remains unknown. We analyzed bone marrow samples from 115 patients with MDS collected prior to HSCT using next-generation sequencing. Seventy-one patients (61%) had at least one mutated gene. We found that patients with a higher number of mutated genes (more than 2) had a worse outcome (2 years overall survival [OS] 54.8% vs. 31.1%, p = 0.035). The only two significant variables in the multivariate analysis for OS were TET2 mutations (p = 0.046) and the development of cGVHD, considered as a time-dependent variable (p < 0.001), correlated with a worse and a better outcome, respectively. TP53 mutations also demonstrated impact on the cumulative incidence of relapse (CIR) (1 year CIR 47.1% vs. 9.8%, p = 0.006) and were related with complex karyotype (p = 0.003). cGVHD improved the outcome even among patients with more than 2 mutated genes (1-year OS 88.9% at 1 year vs. 31.3%, p = 0.02) and patients with TP53 mutations (1-year CIR 20% vs. 42.9%, p = 0.553). These results confirm that cGVHD could ameliorate the adverse impact of somatic mutations in patients with MDS with HSCT.
骨髓增生异常综合征（MDS）患者在接受异基因造血干细胞移植（HSTC）后发生体细胞突变与不良预后相关，但慢性移植物抗宿主病（cGVHD）在这部分患者中的作用尚不清楚。我们分析了 115 例 MDS 患者在 HSTC 前采用下一代测序技术采集的骨髓样本。71 例（61%）患者至少存在 1 个突变基因。我们发现，突变基因数量较多（超过 2 个）的患者预后更差（2 年总生存率 [OS] 54.8% vs. 31.1%，p=0.035）。OS 的多变量分析中仅有两个显著变量，即 TET2 突变（p=0.046）和 cGVHD 的发生，作为一个时间相关变量（p<0.001），分别与较差和较好的预后相关。TP53 突变也对累积复发率（CIR）有影响（1 年 CIR 47.1% vs. 9.8%，p=0.006），与复杂核型相关（p=0.003）。cGVHD 甚至可以改善具有 2 个以上突变基因（1 年 OS 1 年时为 88.9% vs. 31.3%，p=0.02）和 TP53 突变患者（1 年 CIR 20% vs. 42.9%，p=0.553）的不良预后。这些结果证实，cGVHD 可以减轻具有 HSTC 的 MDS 患者体细胞突变的不良影响。
