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Multicenter Study
. 2024 Apr 30;22(1):410.
doi: 10.1186/s12967-024-05114-w.

Measurable residual disease monitoring by ddPCR in the early posttransplant period complements the traditional MFC method to predict relapse after HSCT in AML/MDS: a multicenter retrospective study

Weihao Chen  1 , Jingtao Huang  2   3 , Yeqian Zhao  1   4   5 , Luo Huang  1   4   5 , Zhiyang Yuan  6 , Miner Gu  7 , Xiaojun Xu  7 , Jimin Shi  1   4   5 , Yi Luo  1   4   5 , Jian Yu  1   4   5 , Xiaoyu Lai  1   4   5 , Lizhen Liu  1   4   5 , Huarui Fu  1   4   5 , Chenhui Bao  8 , Xin Huang  8 , Zhongzheng Zheng  6 , He Huang  9   10   11 , Xiaoxia Hu  12   13 , Yanmin Zhao  14   15   16
Affiliations
Multicenter Study

Measurable residual disease monitoring by ddPCR in the early posttransplant period complements the traditional MFC method to predict relapse after HSCT in AML/MDS: a multicenter retrospective study

Weihao Chen et al. J Transl Med. .

Abstract

Background: Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously.

Methods: Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse.

Results: Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001) and lower rates of relapse-free survival (RFS, 55.5% vs. 83.7%, P < 0.001) and overall survival (OS, 60.5% vs. 90.5%, P < 0.001). In multivariate analysis, ddPCR-MRD positivity of non-DTA genes was an independent adverse predictor for CIR (hazard ratio [HR], 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002) and OS (HR, 3.12; P = 0.007). Moreover, the combination of ddPCR with multiparameter flow cytometry (MFC) can further accurately identify patients at high risk of relapse (F+/M+, HR, 22.44; P < 0.001, F+/M-, HR, 12.46; P < 0.001 and F-/M+, HR, 4.51; P = 0.003).

Conclusion: ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC.

Trial registration: ClinicalTrials.gov identifier: NCT06000306. Registered 17 August 2023 -Retrospectively registered ( https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1 ).

Keywords: Allo-HSCT; MFC; MRD; Relapse; ddPCR.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Consort diagram
Fig. 2
Fig. 2
CIR, NRM, RFS, and OS for patients who were MRD positive compared with MRD negative in non-DTA genes by ddPCR after allo-HSCT (150 patients). (A) CIR and NRM by competing risk analysis for MRD-positive (n = 52) and MRD-negative (n = 98) patients. (B, C) RFS and OS by Kaplan-Meier method for MRD-positive (n = 52) and MRD-negative (n = 98) patients
Fig. 3
Fig. 3
Forest plot showing the first (A) and second (B) multivariate analysis for CIR and OS
Fig. 4
Fig. 4
CIR, RFS, and OS for patients who were F+/M+, F-/M+, F+/M-, and F-/M- in non-DTA genes after allo-HSCT by tandem assessment (150 patients). (A, B) CIR and NRM by competing risk analysis for F+/M+ (n = 8), F-/M+ (n = 43), F+/M- (n = 6), and F-/M- (n = 93) patients. (C, D) RFS and OS by Kaplan-Meier method for F+/M+ (n = 8), F-/M+ (n = 43), F+/M- (n = 6), and F-/M- (n = 93) patients
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