Measurable Residual Disease Monitoring During Treatment for Pediatric Acute Myeloid Leukemia in First Relapse

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ABSTRACT Background Survival after relapse in pediatric acute myeloid leukemia (AML) remains poor, highlighting the critical importance of identifying prognostic factors to guide optimal relapse management. Methods We investigated the prognostic impact of multiparameter flow cytometry (MFC) measurable residual disease (MRD) in 188 patients with first relapse after initial treatment according to the NOPHO‐DBH AML 2012 protocol. Results The 4‐year overall survival (OS 4y ) was 44% (95% confidence interval [CI]: 36%–51%). OS 4y was 61% (CI: 51%–69%) in 133/188 patients who received stem cell transplantation (SCT) after reinduction therapy. Nineteen patients treated at the time of molecular relapse showed an excellent OS 4y of 84% (CI: 58%–95%). Patients with hematological relapse and MRD <0.1% after first reinduction course had a superior OS 4y of 69% (CI: 51%–81%) compared to patients with MRD between 0.1% and 4.9% (OS 4y 46%, CI:28%–63%) and MRD ≥5% (OS 4y 16%, CI: 6%–30%), adjusted hazard ratio (HR) 2.2 for MRD 0.1%–4.9%; p = 0.04 and HR 6.0 for MRD ≥5%; p < 0.001. Patients in second complete remission after first reinduction course and MRD <0.1% after second reinduction course had an OS 4y of 70% (CI: 52%–82%) compared to 46% (CI: 19%–70%) in patients with MRD ≥0.1%, HR 2.7; p = 0.048. OS 4y was 71% (CI: 54%–82%) and 31% (CI: 13%–51%) for patients with MRD <0.1% or ≥0.1% prior to SCT, respectively, HR 3.1; p = 0.004. Conclusions This study identifies MFC MRD during reinduction therapy and before SCT as novel and independent predictors of outcome in relapsed pediatric AML.

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