Pre-Transplant Molecular MRD Strongly Predicts Outcome in NPM1-Mutated AML
Analysis of 107 NPM1-mutant AML patients from the UK AML17 trial showed that pre-transplant molecular MRD by RT-PCR powerfully stratified survival: 2-year overall survival was 83% for MRD-negative, 63% for low-level MRD, and only 13% for high-level MRD patients. Combining MRD level with FLT3-ITD status created two prognostic groups with 82% versus 17% survival. T-cell depletion significantly reduced survival in MRD-positive patients, providing actionable guidance for transplant conditioning decisions.
The original study
Molecular MRD status and outcome after transplantation in NPM1-mutated AML.
- Authors
- Dillon R, Hills R, Freeman S, Potter N, Jovanovic J, Ivey A, et al.
- Journal
- Blood
- Type
- Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
- PMID
- 31932839
Original abstract
Relapse remains the most common cause of treatment failure for patients with acute myeloid leukemia (AML) who undergo allogeneic stem cell transplantation (alloSCT), and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry before alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays, which have far greater sensitivity. We analyzed pretransplant blood and bone marrow samples by reverse-transcription polymerase chain reaction in 107 patients with NPM1-mutant AML enrolled in the UK National Cancer Research Institute AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies per 105ABL in the peripheral blood and <1000 copies in the bone marrow aspirate), and high levels of MRD had an estimated 2-year overall survival (2y-OS) of 83%, 63%, and 13%, respectively (P < .0001). Focusing on patients with low-level MRD before alloSCT, those with FLT3 internal tandem duplications(ITDs) had significantly poorer outcome (hazard ratio [HR], 6.14; P = .01). Combining these variables was highly prognostic, dividing patients into 2 groups with 2y-OS of 17% and 82% (HR, 13.2; P < .0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y-OS, 56% vs 96%; HR, 3.24; P = .0005) and in MRD-positive patients (2y-OS, 34% vs 100%; HR, 3.78; P = .003), but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).