CareDx's next-generation sequencing-based assay AlloHeme has demonstrated remarkable accuracy in early detection of relapse following allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to new interim data from the ACROBAT study.
The findings, presented at the 2025 Tandem Meetings in Honolulu by Dr. Monzr M. Al Malki of City of Hope National Medical Center, reveal the test's potential to transform post-transplant monitoring.
Clinical Performance Metrics
The study analyzed 196 patients (141 AML, 55 MDS) using AlloHeme's innovative approach of detecting increased mixed chimerism (iMC) at a 0.2% or greater threshold between consecutive readings. At 12 months post-transplant, the assay demonstrated:
- Sensitivity: 0.93
- Specificity: 0.88
- Positive Predictive Value: 0.58
- Negative Predictive Value: 0.99
- Area Under Curve (AUC): 0.90
Superiority Over Current Standards
AlloHeme significantly outperformed conventional STR-level testing methods. While STR 1% and 5% thresholds showed AUCs of 0.74 and 0.61 respectively, AlloHeme's 0.90 AUC demonstrated markedly superior diagnostic capability. The test's high negative predictive value of 0.99 provides particular confidence in ruling out imminent relapse.
Early Detection Window
Crucially, AlloHeme detected increased mixed chimerism a median of 36 days (IQR 20, 70 days) before clinical relapse in affected patients. This early warning period could prove vital for therapeutic intervention, though Dr. Al Malki noted that further research is needed to determine optimal intervention strategies.
Clinical Impact and Future Implications
"With AlloHeme, we can detect relapse after allogeneic stem cell transplantation prior to conventional methods, giving clinicians the significant lead time they need to intervene sooner," explained Dr. Marica Grskovic, CareDx's chief strategy officer.
The test's predictive power is further emphasized by statistical analysis showing a hazard ratio of 47.5 for relapse in iMC-positive versus negative cases, with nonrelapse mortality as a competing risk.
Dr. Al Malki highlighted the broader implications: "This study gets us one step closer to having a highly reliable molecular biomarker that enables us to assess the status of the stem cell engraftment and predict risk of relapse."
Detailed Results Analysis
Of the patients who tested iMC-positive:
- 25 experienced relapse within 12 months post-transplant
- 18 remained relapse-free during this period
Among iMC-negative patients:
- Only 2 relapsed within 12 months
- 128 remained relapse-free
These results underscore AlloHeme's potential as a valuable tool in post-transplant monitoring, offering clinicians a more accurate and earlier indication of potential relapse compared to current standard methods.
