The Prognostic Value of Early Detection of Minimal Residual Disease as Defined by Flow Cytometry and Gene Mutation Clearance for Myelodysplastic Syndrome Patients After Myeloablative Allogeneic Hematopoietic Stem-Cell Transplantation.

Chang Hou,Shuhui Jiang,Mingqing Zhu,Menglu Yang,Miao Miao,Depei Wu,Yang Xu,Jia Chen,Hongjie Shen,Lili Zhou

doi:10.3389/fonc.2021.700234

Abstract

High relapse incidence remains a major problem for myelodysplastic syndrome (MDS) patients who have received an allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We retrospectively analyzed the correlations between clinical outcomes and minimal residual disease (MRD) by using mutations (MUT) and flow cytometry (FCM) analysis of 115 MDS patients with allo-HSCT. We divided 115 MDS patients into four groups based on molecular genetics and FCM MRD results at day 30 post-HSCT. There were significant differences in the 2-year progression-free survival (PFS) between the FCMhigh MUTpos and FCMlow MUTneg groups (20% vs 79%, P < 0.001). In addition, by univariate analysis, we found that an IPSS-R score ≥4 pre-HSCT (HR, 5.061; P=0.007), DNMT3A mutations (HR, 2.291; P=0.052), TP53 mutations (HR, 3.946; P=0.011), and poor and very poor revised International Prognostic Scoring System (IPSS-R) cytogenetic risk (HR, 4.906; P < 0.001) were poor risk factors for PFS. In multivariate analysis, we found that an IPSS-R score ≥ 4 pre-HSCT (HR, 4.488; P=0.015), DNMT3A mutations (HR, 2.385; P=0.049), positive FCM MRD combined with persistence gene mutations at day 30 (HR, 5.198; P=0.013) were independent risk factors for disease progression. In conclusion, our data indicated that monitoring MRD by FCM combined with gene mutation clearance at day 30 could help in the prediction of disease progression for MDS patients after transplantation.

Highlights

Myelodysplastic syndromes (MDSs) are myeloid neoplasms with highly variable clinical survival outcomes that depend on several prognostic scoring systems based on clinical/hematological parameters [1]
There were already some studies that reported that multiparameter flow cytometry-based minimal residual disease (MRD) could be used as a prognostic marker for predicting relapse in MDS patients [3, 21,22,23]
It was reported that positive flow cytometry (FCM) MRD pre-HSCT had a high risk of overall mortality in MDS patients [24], and other reports showed that monitoring FCM MRD at 30 days post-transplantation was feasible for the prediction of disease progression [3, 4]

Summary

Introduction

Myelodysplastic syndromes (MDSs) are myeloid neoplasms with highly variable clinical survival outcomes that depend on several prognostic scoring systems based on clinical/hematological parameters [1]. It is reported that the incidence of relapse in MDS patients who received MAC allo-HSCT ranged from 14% to 50% [4,5,6], it was essential to monitor minimal residual disease (MRD) regularly. The current detection method of MRD is based on polymerase chain reaction (PCR), multiparametric flow cytometry (MFC), and gene mutation burden, which can assess different time points and provide useful information in patients with myeloid malignancies undergoing allo-HSCT. What’s more, it should be noted that the percentage of blast cells in MDS patients before HSCT was usually more than 5%; it remains unclear when we should carry out MRD detection. The timing, sensitivity, and specificity of MRD monitoring for MDS patients with allo-HSCT still need to be further verified

Methods

Results

Conclusion