WT1基因和流式细胞术监测骨髓增生异常综合征造血干细胞移植后微小残留病的意义

OBJECTIVE: To investigate the clinical significance of minimal residual disease (MRD) monitoring by using WT1 gene and flow cytometry (FCM) in patients with myelodysplastic syndrome (MDS) who receiving allogeneic stem cell transplantation (allo-HSCT). METHODS: WT1 gene and MDS-related abnormal immunophenotype were examined by real-time quantitative polymerase chain reaction (RQ-PCR) and FCM, respectively. The bone marrow samples were collected from patients with MDS who received allo-HSCT from Feb, 2011 to Oct, 2015 in Peking University People's Hospital before and after transplantation. RESULTS: Among 92 MDS patients, 40 (48.2%) patients were positive for WT1 (WT1(+)) and 9 (10.8%) patients were positive for flow cytometry (FCM(+)). 27 patients (29.3%) met the criteria of our combinative standard, MRDco (MRDco(+)). Only FCM(+) post-transplant (P<0.001) and MRDco(+) (P=0.017) were associated with relapse. The cumulative incidence of relapse (CIR) at 2 years were 66.7% and 1.2% (P<0.001) in FCM(+) and FCM(−) groups. MRDco(+) group had a 2-year CIR of 23.0% while MRDco(−) group had a 2-year CIR of 1.6% (P=0.004). The specificity of post-transplant WT1, FCM and MRDco to predict relapse was 59.0%, 96.4% and 74.7%, respectively. The sensitivity of these three MRD parameters to predict relapse was 66.7%. CONCLUSION: Post-transplant FCM and MRDco are useful tools to monitor MRD for MDS after transplantation. The preemptive intervention based on MRDco is able to reduce the relapse rate.