KEY TAKEAWAYS
- The study aimed to assess ddPCR-MRD feasibility post-allo-HSCT, targeting multiple molecular markers simultaneously.
- The study concluded that ddPCR-MRD is viable for relapse prediction post-allo-HSCT in AML/MDS, particularly when combined with MFC.
Despite the widespread application of droplet digital PCR (ddPCR) in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AM), there remains a dearth of studies exploring its feasibility of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly when assessing multiple molecular markers simultaneously.
Weihao Chen and the team aimed to evaluate the feasibility of ddPCR-MRD monitoring following allo-HSCT, focusing on simultaneously assessing multiple molecular markers.
The study gathered samples from patients with AML or high-risk myelodysplastic syndrome (MDS) who achieved complete remission after undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2018 and August 2021. The aim was to assess whether posttransplant ddPCR-MRD monitoring could pinpoint individuals at a heightened risk of relapse.
The results revealed that among the 152 patients analyzed, 58 (38.2%) tested positive for measurable residual disease (MRD) by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. Notably, the presence of detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT did not correlate with an elevated risk of relapse. Excluding DTA mutations, patients displaying ddPCR-MRD positivity exhibited a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001), alongside 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).
Multivariate analysis further identified ddPCR-MRD positivity of non-DTA genes as an independent adverse predictor for CIR (HR, 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002), and OS (HR, 3.12; P = 0.007). Additionally, combining ddPCR with multiparameter flow cytometry (MFC) enhanced the accuracy of identifying 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).
The study concluded that ddPCR-MRD represents a viable strategy for predicting relapse following allo-HSCT in patients with AML or high-risk MDS who lack detectable DTA mutations. Furthermore, combining ddPCR with MFC improves predictive accuracy.
The trial was sponsored by the Zhejiang University.
Source: https://pubmed.ncbi.nlm.nih.gov/38689269/
Clinical Trial: https://clinicaltrials.gov/study/NCT06000306
Chen, W., Huang, J., Zhao, Y., et al. (2024) “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.” J Transl Med 22, 410 (2024). https://doi.org/10.1186/s12967-024-05114-w
