Introduction:
Early relapse after stem cell transplantation (SCT) remains common in PTCL. Improved biomarkers may better select patients for SCT in PTCL. Molecular residual disease (MRD) can inform decisions around SCT, but its utility is limited by confounding clonal hematopoiesis mutations, and a heterogeneous mutational landscape. We hypothesized that lineage-informed, personalized MRD detection in pre-SCT apheresed T-cells may predict early relapse post-SCT.
Methods:
Eligible PTCL patients underwent either consolidative autologous or allogenic SCT. All patients had an available autologous stem cell apheresis product FACS-sorted into T-, myeloid, and NK/B-cell populations. WES was performed on a diagnostic PTCL biopsy to identify patient-specific variants. These variants were integrated into a panel of canonical PTCL genes to form custom sequencing panels. Lineage-informed MRD (LI-MRD) was determined by CAPP-Seq profiling of pre-SCT apheresis sorted T-cells (T-MRD) and filtration of variants detected in myeloid and NK/B-cell lineages.
Results:
20 AITL and 2 PTCL-NOS cases were included. A median of 25 SNVs per patient were used in T-MRD detection. Multiple mutations, including known clonal hematopoiesis variants, were detected across sorted cellular lineages in non-relapsing patients. Removal of those mutations significantly improved MRD performance in predicting relapse, with 9/10 LI-MRD+ patients relapsing post-SCT (median time-to-relapse 4.8m), versus 3/12 LI-MRD-negative patients (specificity 88.9%, sensitivity 75%, PPV 90%). LI-MRD-negativity was associated with superior PFS (p=0.007, HR 5.1, 95% CI:1.4-19.2). Higher levels of LI-MRD was associated with inferior PFS (p=0.006).
Conclusion:
Personalized LI-MRD improves MRD specificity, and LI-MRD positivity at the time of SCT is associated with increased relapse risk post-SCT.
