Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive
Eduardo Ramos Elbal1, José Luis Fuster1, José Antonio Campillo2
1Pediatric Oncohematology Department, Clinic University Hospital Virgen de la Arrixaca and Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120, Murcia, Spain.
Purpose:
Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse.
Methods:
In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR).
Results:
Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively.
Conclusions:
MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed.
Insights
Measurable residual disease (MRD) monitoring using MFC, FISH, and PCR can predict childhood acute myeloid leukemia (AML) relapse. However, current pre-emptive therapies are insufficient, necessitating more sensitive methods and effective treatments.
Area of Science:
- Pediatric Hematology Oncology
- Cancer Genomics
- Immunology
Background:
- Childhood acute myeloid leukemia (AML) outcomes have improved, but relapse remains a challenge, affecting approximately one-third of patients.
- Measurable (or minimal) residual disease (MRD) monitoring is crucial for guiding therapeutic adjustments and pre-emptive treatments to prevent overt hematological relapse.
Purpose of the Study:
- To evaluate the effectiveness of multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR) in monitoring MRD for predicting relapse in pediatric AML.
- To assess the timing of relapse detection by different MRD monitoring methods and the efficacy of pre-emptive therapies.
Main Methods:
- Analysis of 297 bone marrow samples from 20 pediatric AML patients.
- Utilized three MRD monitoring techniques: MFC, FISH, and PCR.
- Correlated MRD detection with patient survival, relapse rates, and time to relapse.
Main Results:
- Three-year overall survival was 73% and event-free survival was 68%, with a 25% global relapse rate.
- All relapses were preceded by detectable MRD using MFC, PCR, and/or FISH.
- Median times from MRD detection to relapse varied by method: 26 days (MFC), 111 days (PCR/FISH), and 140 days (WT1 expression).
Conclusions:
- MFC, FISH, and PCR are valuable complementary tools for anticipating childhood AML relapse weeks to months in advance.
- Pre-emptive therapies in this study did not prevent disease progression, highlighting a need for improvement.
- Development of more sensitive MRD monitoring techniques and effective pre-emptive therapies is essential for improving pediatric AML outcomes.
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