Are minimal residual disease measurement after consolidation therapy useful in children with acute lymphoblastic leukemia?

Abstract Minimal residual disease (MRD) is regularly measured at later timepoints after end of first consolidation (EOC) in children with acute lymphoblastic leukemia (ALL). The question remains whether this is useful for detecting (molecular) relapse. We investigated the clinical relevance of MRD after EOC in intermediate risk patients treated on DCOG-ALL-10 (n = 271) and DCOG-ALL-9 (n = 122), with MRD < 0.05% at EOC. EOC MRD negative patients (n = 178) had excellent outcomes, irrespective of MRD results at later timepoints; 6-years relapse free survival (6y-RFS) of 92.0% (95% CI:88–97) for those with MRD negativity at all later timepoints compared to 96.2% (95% CI:89–100) for those with one or more later timepoints being positive (p = 0.46). Patients with positive EOC MRD (n = 91) of whom the subsequent timepoints were MRD negative (n = 43), had comparable good outcomes, 6y-RFS of 93.0% (95% CI:85–100). Patients being MRD positive at EOC and MRD positivity at one or more subsequent timepoints (n = 48) had a higher risk of relapse, 6y-RFS 70.5% (95% CI:58–84), p = 0.002. These findings were confirmed in the validation cohort of ALL-9. In patients who are MRD negative at EOC, MRD measurements at later timepoints can be abandoned. For patients who are EOC MRD positive the subsequent MRD measurement might be informative for further risk stratification.