Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should...

Area of Science:

• Hematology
• Oncology
• Immunology

Background:

• Minimal residual disease (MRD) detection pre-hematopoietic cell transplant (HCT) and acute graft-versus-host disease (aGvHD) are known independent predictors of relapse in pediatric acute lymphoblastic leukemia (ALL).
• Further defining risk stratification requires assessing the timing of relapse and the influence of leukemia risk category and post-HCT MRD.

Purpose of the Study:

• To further refine risk stratification in pediatric ALL patients undergoing HCT by analyzing the interplay of pre-HCT MRD, aGvHD timing, leukemia risk category, and post-HCT MRD.
• To identify optimal windows for intervention to prevent relapse post-HCT.

Main Methods:

• Multivariate analysis was employed to assess the impact of pre-HCT MRD (<0.1% vs ⩾0.1%), aGvHD by day +55, leukemia risk category, and post-HCT MRD on relapse, event-free survival (EFS), and overall survival (OS).
• Comparative analysis of survival outcomes based on combinations of pre-HCT MRD and aGvHD status was performed.

Main Results:

• Pre-HCT MRD <0.1% and aGvHD by day +55 were associated with decreased relapse and improved EFS.
• Intermediate leukemia risk status predicted decreased relapse, improved EFS, and OS.
• Patients with pre-HCT MRD ⩾0.1% without aGvHD had significantly worse survival compared to those with pre-HCT MRD <0.1% and aGvHD.
• Post-HCT MRD substantially increased relapse risk (HR=4.5, P<0.01).
• An optimal window for intervention to prevent relapse was identified between day +55 and +200 post-HCT.

Conclusions:

• High-risk relapse patients post-HCT can be accurately defined using leukemia risk category, pre- and post-HCT MRD status, and the occurrence of aGvHD.
• Early detection of MRD and monitoring for aGvHD are crucial for risk stratification and guiding therapeutic interventions in pediatric ALL post-HCT.