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

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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Journal
Pediatric Blood & Cancer
Published
2026-07-27
DOI
https://doi.org/10.1002/1545-5017.70513
Primary Topic
Acute Myeloid Leukemia Research
Type
article
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article

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

H Hasle, Zhanna Kovalova, Kristian Juul-Dam, Kristian Juul Sandahl et al.
Pediatric Blood & Cancer
Acute Myeloid Leukemia Research
article

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

H Hasle, Zhanna Kovalova, Kristian Juul-Dam, Kristian Juul Sandahl, Linda Fogelstrand, Josefine Palle, Gertjan J.L. Kaspers, Ulrika Norén‐Nyström, Lene Karlsson, Kadri Saks, Jonas Abrahamsson, Barbara De Moerloose, Cornelis Jan Pronk, Ramunė Pasaulienė, Camilla Poulsen, B F Goemans, Anne Tierens, J Navarrete Navarro, Monica Cheng Munthe‐Kaas, Daniel Cheuk, Kirsi Jahnukainen, Nira Arad‐Cohen
article en

Abstract

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.

Pediatric Blood & Cancer
Uppsala University (SE), Oslo University Hospital (NO), University Health Network (CA), University of Helsinki (FI), Vilnius University (LT), Lund University (SE), Helsinki University Hospital (FI), Hong Kong Federation of Youth Groups (CN), Hong Kong Adventist Hospital (CN), Sahlgrenska University Hospital (SE), Ghent University Hospital (BE), Rambam Health Care Campus (IL), Aarhus University Hospital (DK), Hospital Universitari i Politècnic La Fe (ES), Duchess of Kent Children's Hospital (CN), East Tallinn Central Hospital (EE), Emma Kinderziekenhuis (NL), Children's Clinical University Hospital (LV), Riga Stradiņš University (LV), Princess Máxima Center (NL), Skåne University Hospital (SE), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), University of Hong Kong (HK), Umeå University (SE)
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