Peripheral Blood Tumor Associated Cell-Free DNA Testing as a Predictor for Relapse Postallogeneic Stem Cell...

Area of Science:

• Hematology
• Oncology
• Genomics

Background:

• Allogeneic stem cell transplantation (allo-SCT) offers a curative approach for acute myelogenous leukemia (AML).
• Relapse remains a significant challenge post-allo-SCT, necessitating improved monitoring strategies.
• Minimal residual disease (MRD) detection via tumor-associated circulating cell-free DNA (TA-cfDNA) is an emerging method to predict relapse.

Purpose of the Study:

• To investigate the association between TA-cfDNA presence in peripheral blood (PB) and post-transplant outcomes in AML patients.
• To evaluate the prognostic value of specific TA-cfDNA mutation risks (adverse vs. intermediate) on overall survival (OS) and relapse-free survival (RFS).

Main Methods:

• Retrospective study of 90 AML patients undergoing allo-SCT between 2018-2022.
• PB TA-cfDNA analysis performed between Day 100-200 post-transplantation using commercial genomic sequencing.
• Kaplan-Meier analysis assessed the correlation of TA-cfDNA positivity and mutation risk with OS and RFS.

Main Results:

• TA-cfDNA positivity at Day 150±50 was significantly associated with worse OS (HR 5.4) and RFS (HR 5.2) compared to TA-cfDNA negative patients.
• Adverse mutations detected in TA-cfDNA at Day 150±50 correlated with substantially worse OS (HR 11.2) and RFS (HR 11.6).
• The presence of TA-cfDNA and high-risk mutations strongly predicts increased relapse rates and mortality post-allo-SCT.

Conclusions:

• Peripheral blood TA-cfDNA detection is a powerful predictive marker for relapse and mortality in AML patients post-allo-HSCT.
• Persistent high-risk mutations in TA-cfDNA are linked to poor survival outcomes.
• TA-cfDNA monitoring holds potential for early intervention and optimizing post-transplant treatment strategies.