Implication of Post-Induction Minimal Residual Disease in the Management of Pediatric Acute Lymphoblastic Leukemia in a Resource-Limited Setting

TL;DR

This study shows that measuring minimal residual disease (MRD) on Day 29 helps assess treatment response in children with leukemia, especially in areas with limited resources.

Contribution

The study introduces Day 29 MRD as a cost-effective tool for managing pediatric ALL in resource-limited settings.

Findings

85.6% of patients had negative MRD on Day 29 and continued the same treatment regimen.

MRD results strongly correlated with interim bone marrow assessments.

Day 29 MRD evaluation is proposed as a single best tool for response evaluation in resource-limited areas.

Abstract

Background: Minimal residual disease (MRD) measurement in pediatric acute lymphoblastic leukemia (ALL) is the most powerful tool for treatment response assessment.

Objective: This study aims to assess the implications of post-induction Day 29 MRD evaluation in the management of pediatric ALL within a resource-limited setting and its correlation with interim Day 8/15 bone marrow assessment.

Materials and methods: A prospective analytical study was conducted at the pediatric hematology oncology department from January 1​​​, ​2022, to December 31​​​​​, 2022. Flowcytometry-based newly diagnosed ALL patients aged 1-16 years were included. MRD assessment on Day 29 of induction and interim bone marrow evaluations on Day 8/15 were performed according to the UKALL-2019 protocol.

Results: Out of 578 patients, 407 (70.4%) were males, and 171 (29.6%) were females. The predominant age group was 5-10 years, including 324 (56.0%) patients. Flow cytometry revealed pre-B ALL in 468 (81.0%) and pre-T ALL in 110 (19.0%). High-risk patients receiving four-drug induction numbered 379 (65.6%), while 199 (34.4%) were standard risk. Interim bone marrow response was M2 in 502 (86.9%) and M3 in 73 (12.6%). Post-induction Day 29 MRD was < 0.01% (negative) in 495 (85.6%) patients who continued the same regimen, and >0.01% (positive) in 83 (14.4%) requiring treatment escalation. Among those with M3 interim marrow response, 42 (7.3%) were high-risk and MRD-positive. Induction mortality occurred in 32 (5.5%) patients, and treatment abandonment occurred in 46 (8.0%).

Conclusion: Our study has demonstrated significant induction remission response in ALL by achieving negative MRD, which correlates strongly with interim bone marrow assessment, proposing Day 29 MRD as a single best cost-effective tool for response evaluation in resource-limited settings.