What question did this study set out to answer?

The study aims to evaluate the prognostic significance of NPM1-mut MRD and determine effective thresholds for predicting relapse in acute myeloid leukemia.

April 12, 2026

Real‐World Outcomes in NPM1 ‐Mutated Acute Myeloid Leukemia: The Impact of Measurable Residual Disease on Disease Relapse

Key Points

The study aims to evaluate the prognostic significance of NPM1-mut MRD and determine effective thresholds for predicting relapse in acute myeloid leukemia.
Analyzed data from 141 patients with NPM1-mut AML from the Hellenic AML-Registry.
Measured MRD levels using RT-qPCR after the second induction chemotherapy cycle.
Assessed outcomes such as relapse-free survival (RFS) and overall survival (OS) based on MRD levels.
MRD positivity at various thresholds significantly correlated with relapse risk.
Patients with ≥ 0.1% MRD were at high risk for relapse, requiring early intervention.
Low-level MRD patients (< 0.01%) could be closely monitored without immediate treatment.

Abstract

The prognostic value of NPM1-mut Measurable Residual Disease (MRD) has been increasingly recognized. However, real-world data validating the prognostic impact of NPM1-mut MRD remains limited. The aim of this study was to assess the prognostic value of NPM1-mut MRD and to explore optimal MRD thresholds for relapse prediction. One hundred forty-one patients with newly diagnosed NPM1-mut AML, from the Hellenic AML-Registry, in CR/CRi after the second cycle of induction and with bone marrow (BM) MRD assessment by RT-qPCR, were included in our study. Allogeneic stem cell transplantation (allo-SCT) in CR1 was not associated with any difference in RFS or OS between patients who achieved < 0.1% mutNPM1/ABL after the second cycle of chemotherapy, suggesting that this cut-off may effectively stratify relapse risk and possibly guide optimal use of allo-SCT. End-of-treatment (EOT) and during follow-up MRD assessment exhibited equally significant prognostic value, with high-level MRD positivity (≥ 0.1% mutNPM1/ABL) requiring early intervention to avoid imminent relapse, while those with undetectable or very low-level MRD (< 0.01% mutNPM1/ABL) being able to be safely monitored with no further intervention. Patients with low-level MRD positivity (≥ 0.01% and < 0.1%) require close MRD monitoring due to the substantial risk for progression to high-level MRD positivity. Overall, our results confirm the prognostic value of MRD assessment in BM samples at certain time points, with the cut-off of 0.1% after two cycles of chemotherapy enabling risk stratification and possibly informing transplant decisions, and during follow-up the cut-off of 0.01% being able to predict the 6-month relapse risk and guide further clinical management.

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