Persistent Malignant Stem Cells Drive Relapse After Transplantation in the Myelodysplastic Neoplasms

Ultra-low-input DNA sequencing detected MDS HSC mutations a mean of 98 days before relapse, with relapse risk strongly predicted (95.7% vs 30.3%; hazard ratio 8.8; P=1.5e-7) in a multicenter post-transplant cohort.

• Why it matters: Relapse after allogeneic transplantation remains common, and clinicians lack a sensitive way to track rare, transplant-resistant MDS stem cells before clinical recurrence.
• What they did: The study used an ultra-low-input DNA sequencing assay on post-transplant samples, compared mutation detection in HSCs versus unfractionated marrow, and added donor-host HSC chimerism measurements plus single-cell protein/DNA/RNA with mitochondrial lineage tracing.
• The result: HSC mutation detection preceded relapse and improved sensitivity, while mutations confined to unfractionated marrow did not predict relapse; venetoclax/azacytidine depleted detectable MDS HSCs in longitudinally evaluated patients, supporting preemptive intervention.

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