Measurable Residual Disease Monitoring During Treatment for Pediatric Acute Myeloid Leukemia in First Relapse
Camilla Poulsen1, Kristian Juul Sandahl1, Lene Karlsson2
1Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
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 (OS4y) was 44% (95% confidence interval [CI]: 36%-51%). OS4y 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 OS4y of 84% (CI: 58%-95%). Patients with hematological relapse and MRD <0.1% after first reinduction course had a superior OS4y of 69% (CI: 51%-81%) compared to patients with MRD between 0.1% and 4.9% (OS4y 46%, CI:28%-63%) and MRD ≥5% (OS4y 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 OS4y of 70% (CI: 52%-82%) compared to 46% (CI: 19%-70%) in patients with MRD ≥0.1%, HR 2.7; p = 0.048. OS4y 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.
Insights
Measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) during reinduction therapy and before stem cell transplantation (SCT) are key predictors of survival in pediatric acute myeloid leukemia (AML) relapse. Lower MRD levels significantly correlate with improved overall survival rates.
Area of Science:
- Hematology
- Pediatric Oncology
- Cancer Research
Background:
- Survival rates for pediatric acute myeloid leukemia (AML) after relapse are critically low.
- Identifying prognostic factors is essential for optimizing treatment strategies in relapsed AML.
Purpose of the Study:
- To investigate the prognostic significance of multiparameter flow cytometry (MFC) measurable residual disease (MRD) in pediatric patients with relapsed AML.
- To determine if MFC MRD levels during reinduction therapy and before stem cell transplantation (SCT) can predict patient outcomes.
Main Methods:
- A cohort of 188 pediatric patients with first relapse of AML were analyzed.
- Multiparameter flow cytometry (MFC) was used to assess measurable residual disease (MRD) levels.
- Survival data was analyzed in relation to MRD status at different time points during reinduction therapy and before SCT.
Main Results:
- The 4-year overall survival (OS4y) for the cohort was 44%.
- Patients achieving MRD <0.1% after the first reinduction course had a significantly better OS4y (69%) compared to those with higher MRD levels.
- MRD levels <0.1% before SCT were associated with a higher OS4y (71%) compared to MRD ≥0.1% (31%).
Conclusions:
- Multiparameter flow cytometry (MFC) measurable residual disease (MRD) is a novel and independent predictor of outcome in relapsed pediatric AML.
- MRD assessment during reinduction therapy and prior to SCT can guide treatment decisions and improve patient survival.
