Molecular MRD status and outcome after transplantation in NPM1 mutated AML

Richard Dillon, Robert K Hills, Sylvie D Freeman, Nicola Potter, Jelena Jovanovic, Adam Ivey, Anju Kanda, Manohursingh Runglall, Nicola Foot, Mikel Valganon, Asim Khwaja, Jamie Cavenagh, Matthew L Smith, Hans Beier Ommen, Ulrik Overgaard, Mike Dennis, Steven Knapper, Harpreet Kaur, David C Taussig, Priyanka MehtaKavita Raj, Igor Novitzky-Basso, Emmanouil Nikolousis, Robert D Danby, Pramila Krishnamurthy, Kate Hill, Damian Finnegan, Samah Alimam, Erin Hurst, Peter Johnson, Anjum Bashir Khan, Rahuman Salim, Charles F Craddock, Ruth Lilian Spearing, Amanda Frances Gilkes, Rosemary E Gale, Alan Kenneth Burnett, Nigel H Russell, David Grimwade

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)
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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 10 5 ABL 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 5.01). 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 5.0005) and in MRD-positive patients (2y-OS, 34% vs 100%; HR, 3.78; P 5.003), but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (

Original languageEnglish
Pages (from-to)680-688
Number of pages9
Issue number9
Early online date27 Feb 2020
Publication statusPublished - 27 Feb 2020


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