Next-generation sequencing-based MRD in adults with ALL undergoing hematopoietic cell transplantation

Area of Science:

• Hematology
• Oncology
• Transplant Immunology

Background:

• Measurable residual disease (MRD) is a known adverse prognostic factor in adult acute lymphoblastic leukemia (ALL) patients undergoing hematopoietic cell transplant (HCT).
• Next-generation sequencing (NGS) offers highly sensitive detection of MRD (10^-6), but its prognostic value in this specific patient population is understudied.

Purpose of the Study:

• To evaluate the prognostic significance of NGS-based MRD in adult ALL patients undergoing allogeneic HCT.
• To determine if pre-transplant (MRDpre) and post-transplant (MRDpost) MRD levels predict leukemia relapse and survival.

Main Methods:

• Retrospective analysis of 158 adult ALL patients who underwent allogeneic HCT at two major centers (Stanford University and Oregon Health & Science University) between 2014 and 2021.
• MRD assessment using the NGS-based clonoSEQ assay was performed pre-HCT and up to one year post-HCT.
• Patients were followed for relapse and survival for up to two years post-HCT.

Main Results:

• Increased cumulative incidence of relapse was observed across all levels of MRDpre, even at levels below 10^-4 (HR, 3.56).
• Detectable MRDpost was the strongest predictor of relapse in multivariable analysis (HR, 4.60).
• In B-cell ALL patients, post-HCT immunoglobulin H (IgH) MRD clonotypes were more associated with relapse than non-IgH MRD clonotypes.

Conclusions:

• NGS-based MRD detection, even at low levels (10^-6), provides significant prognostic value in adult ALL patients undergoing HCT.
• Post-transplant MRD is a critical indicator for predicting relapse risk and guiding clinical management.
• Specific MRD clonotype detection (IgH) may offer further insights in B-cell ALL patients.