IgH-V(D)J NGS-MRD measurement pre- and early post- allo-transplant defines very low and very high risk ALL patients.

Publication Type:

Journal Article

Source:

Blood (2015)

Abstract:

Positive detection of minimal residual disease (MRD) by multichannel flow cytometry (MFC) prior to hematopoietic cell transplantation (HCT) of patients with ALL identifies patients at high risk for relapse, but many pre-HCT MFC-MRD negative patients also relapse, and the predictive power MFC-MRD early post-HCT is poor. To test whether the increased sensitivity of next-generation sequencing (NGS-MRD) better identifies pre- and post-HCT relapse risk, we performed IgH V(D)J NGS-MRD on 56 patients with B-cell ALL enrolled in Children's Oncology Group (COG) trial ASCT0431. NGS-MRD predicted relapse and survival more accurately than MFC-MRD (p<0.0001), especially in the MRD negative cohort (relapse 0% vs. 16%; p=0.02, 2yr OS 96% vs. 77%; p=0.003). Post-HCT NGS-MRD detection was better at predicting relapse than MFC-MRD (p<0.0001), especially early after HCT (day 30 MFC-MRD positive relapse rate 35%, NGS-MRD positive relapse rate 67%;p=0.004). Any post-HCT NGS positivity resulted in an increase in relapse risk by multivariate analysis (HR 7.7; p=0.05). Absence of detectable IgH V(D)J NGS-MRD pre-HCT defines good risk patients potentially eligible for less intense treatment approaches. Post-HCT NGS-MRD is highly predictive of relapse and survival, suggesting a role for this technique in defining patients early who would be eligible for post-HCT interventions.