Not just useful in treatment selection: Minimal residual disease levels after remission can predict long-term outcomes

This study examined the effect of minimal residual disease (MRD) levels at various time points on clinical outcomes in children with acute lymphoblastic leukemia (ALL). Researchers concluded that MRD levels during and after remission can predict ALL outcomes.

ALL is a type of cancer in which the bone marrow makes too many lymphoblasts (a type of immature white blood cell). This type of cancer tends to get worse quickly if it is not treated. Chemotherapy is often the first-line treatment for ALL. Some patients can be successfully treated with low-intensity therapy, while others require intensified therapy to reduce the risk of relapse. Finding predictors of treatment success is important to help select appropriate therapies for patients.

Minimal residual disease (MRD) refers to small numbers of leukemia cells that remain in the patient during or after treatment. It is often used to help select appropriate treatment strategies for patients. The role of MRD levels during and after remission in predicting long-term outcomes is still being studied.

The aim of this study was to examine the link between MRD levels during and after remission on clinical outcomes in children with ALL.

498 children with newly diagnosed ALL were included in this study. MRD was measured on Days 19 and 46 after the start of induction (treatment to induce remission). After the start of remission, patients were classified into risk groups based on standard features. Additional measurements of MRD were made on Week 7 of maintenance therapy (therapy lasting approximately 2 years with the aim to maintain remission) and on Weeks 17, 48, and 120 (end of treatment).

Patients with 1% or greater MRD on Day 19 were significantly more likely to have a treatment-related event such as progression, death, or needing to stop= treatment at 10 years. 69.2% of low-risk patients with 1% or greater MRD on Day 19 were event-free at 10 years. It was 95.5% for low-risk patients with lower MRD levels. Standard-risk patients had a 10-year event-free survival of 65.1% if they had an MRD of 1% or greater and 82.9% if MRD was lower than 1%.

12 low-risk ALL patients with 1% or greater MRD on Day 19 but negative MRD on Day 46 were treated for standard-risk disease. They had a 10-year event-free survival of 88.9%. 244 low-risk patients reached MRD levels less than 1% on Day 19. This predicted an excellent 10-year event-free survival of 95.5%, regardless of MRD levels on Day 46.

Among standard-risk patients with MRD of less than 1% on Day 19, the 15 patients with persistent MRD on Day 46 had a lower 10-year event-free survival (72.7%) compared to the 126 patients with negative MRD on Day 46 (84%).

4 (of 382 available patients) showed MRD on Week 7 after achieving negative MRD during remission. MRD re-emerged in 1 (of 448) at Week 17 and in 1 (of 437) at Week 48. 5 of these 6 patients died despite additional treatment. At the end of therapy (Week 120), all 430 available patients had undetectable MRD, but 26 patients later developed a relapse. The average time to relapse after completing therapy was 19 months.

Researchers concluded that MRD levels during and after remission can predict ALL outcomes. Researchers advised that MRD should be monitored to guide treatment action in patients who achieve remission but have detectable MRD.