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移植后骨髓纤维化患者分子残留病的影响。

Impact of molecular residual disease post allografting in myelofibrosis patients.

机构信息

Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Department of Hematology and Oncology, University Hospital Göttingen, Göttingen, Germany.

出版信息

Bone Marrow Transplant. 2017 Nov;52(11):1526-1529. doi: 10.1038/bmt.2017.157. Epub 2017 Jul 17.

Abstract

We screened 136 patients with myelofibrosis and a median age of 58 years who underwent allogeneic stem cell transplantation (AHSCT) for molecular residual disease for JAKV617F (n=101), thrombopoietin receptor gene (MPL) (n=4) or calreticulin (CALR) (n=31) mutation in peripheral blood on day +100 and +180 after AHSCT. After a median follow-up of 78 months, the 5-year estimated overall survival was 60% (95% confidence interval (CI): 50-70%) and the cumulative incidence of relapse at 5 years was 26% (95% CI: 18-34%) for the entire study population. The percentage of molecular clearance on day 100 was higher in CALR-mutated patients (92%) in comparison with MPL- (75%) and JAKV617F-mutated patients (67%). Patients with detectable mutation at day +100 or at day +180 had a significant higher risk of clinical relapse at 5 years than molecular-negative patients (62% vs 10%, P<0.001) and 70% vs 10%, P<0.001, respectively) irrespectively of the underlying mutation. In a multivariate analysis, high-risk diseases status (hazard ratio (HR) 2.5; 95% CI: 1.18-5.25, P=0.016) and detectable MRD at day 180 (HR 8.36, 95% CI: 2.76-25.30, P<0.001) were significant factors for a higher risk of relapse.

摘要

我们对 136 名中位年龄为 58 岁的骨髓纤维化患者进行了筛查,这些患者在接受异基因造血干细胞移植(AHSCT)后,于+100 天和+180 天对 JAKV617F(n=101)、血小板生成素受体基因(MPL)(n=4)或钙网蛋白(CALR)(n=31)外周血中的分子残留疾病进行了检测。在中位随访 78 个月后,整个研究人群的 5 年估计总生存率为 60%(95%置信区间(CI):50-70%),5 年累积复发率为 26%(95%CI:18-34%)。CALR 突变患者(92%)的分子清除率在第 100 天高于 MPL 突变患者(75%)和 JAKV617F 突变患者(67%)。在第+100 天或第+180 天检测到突变的患者在 5 年内发生临床复发的风险显著高于分子阴性患者(62%对 10%,P<0.001)和 70%对 10%,P<0.001),与潜在突变无关。在多变量分析中,高危疾病状态(危险比(HR)2.5;95%CI:1.18-5.25,P=0.016)和第 180 天可检测到的 MRD(HR 8.36,95%CI:2.76-25.30,P<0.001)是复发风险较高的显著因素。

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