End-of-induction MRD predicts early survival in high-risk adult B-acute lymphoblastic leukemia: A study from Eastern
Prakhar Gupta1, Meghna Tyagi2, Subhajit Brahma2
1Department of Molecular Pathology, Tata Medical Centre, Kolkata, West Bengal-700156, India.
Abstract:
Measurable residual disease (MRD) monitoring has dramatically improved outcomes in pediatric acute lymphoblastic leukemia (ALL) patients while, the prognosis in adult B-ALL remains poor. Biological heterogeneity, therapy-related toxicity, and inconsistent MRD-integration contribute to this disparity. This study evaluates the early prognostic value of MRD by flow cytometry in high-risk adult B-ALL patients.
Methods:
The present study included 47 high-risk adult B-ALL patients stratified by cytogenetic-risk groups (Age range: 18 - 66 years) and treated between January 2020 and December 2024 at Tata Medical Center, Kolkata. MRD was assessed using an 11-color flow cytometry panel at end-of-induction (EOI) and end-of-consolidation (EOC) timepoints. Patient details including demographics, cytogenetic risk profiles, treatment protocols, and survival outcomes were collected. Statistical analysis was performed using univariable, multivariable (MANNOVA) and multivariable cox-regression tests. Kaplan-Meier analysis was performed for survival at 18-months.
Results:
At EOI time point, 27 patients were MRD-negative, while 20 had detectable MRD (4 low-level <0.01%, 16 high-level ≥0.01%). MRD positivity at EOI significantly correlated with inferior survival at 18 months (log-rank p = 0.004). On univariable cox regression, EOI MRD positive patients demonstrated an approximately six-fold higher hazard of relapse or death compared with MRD-negative patients (HR = 6.33; 95% CI, 0.39-103.07). Multivariable and cox-regression analysis confirmed EOI MRD positivity as an independent predictor of OS (p = 0.004). Additionally, Day 8 prednisone response showed prognostic significance with survival (cox-regression p-value = 0.003; MANNOVA p ≈ 0.05).
Conclusions:
The EOI MRD positivity, is a robust independent predictor of 18m-survival in high-risk adult B-ALL patients. Additionally, a longitudinal MRD monitoring enhances risk stratification and informs therapeutic decisions. Therefore, incorporating MRD assessment into routine clinical practice is essential for dynamic risk stratification and optimizing outcomes in High-risk adult B-ALL.
Insights
Measurable residual disease (MRD) monitoring at end-of-induction is a strong predictor of survival in adult B-acute lymphoblastic leukemia (B-ALL). Early MRD detection helps in dynamic risk stratification and guides treatment decisions for better patient outcomes.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Prognosis for adult B-acute lymphoblastic leukemia (B-ALL) remains poor compared to pediatric ALL.
- Biological heterogeneity, treatment toxicity, and inconsistent monitoring of measurable residual disease (MRD) contribute to this disparity.
- Early prognostic markers are crucial for improving outcomes in high-risk adult B-ALL.
Purpose of the Study:
- To evaluate the early prognostic value of MRD detected by flow cytometry in high-risk adult B-ALL patients.
- To assess the correlation between MRD status at end-of-induction (EOI) and survival outcomes.
- To determine if MRD positivity is an independent predictor of overall survival (OS).
Main Methods:
- A cohort of 47 high-risk adult B-ALL patients was studied.
- MRD was assessed using an 11-color flow cytometry panel at end-of-induction (EOI) and end-of-consolidation (EOC).
- Statistical analyses included univariable, multivariable (MANNOVA), and multivariable cox-regression tests, along with Kaplan-Meier survival analysis at 18 months.
Main Results:
- MRD positivity at EOI was detected in 20 out of 47 patients (4 low-level, 16 high-level).
- EOI MRD positivity significantly correlated with inferior 18-month survival (log-rank p = 0.004).
- EOI MRD positivity was confirmed as an independent predictor of OS (p = 0.004), with a higher hazard of relapse or death.
Conclusions:
- End-of-induction MRD positivity is a robust, independent predictor of 18-month survival in high-risk adult B-ALL.
- Longitudinal MRD monitoring enhances risk stratification and informs therapeutic decisions.
- Integrating MRD assessment into routine clinical practice is essential for optimizing outcomes in high-risk adult B-ALL.
