Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study.

Dillon, Richard, Hills, Robert K, Freeman, Sylvie D, Potter, Nicola, Jovanovic, Jelena, Ivey, Adam, Kanda, Anju Shankar, Runglall, Manohursingh, Foot, Nicola, Valganon, Mikel, Khwaja, Asim, Cavenagh, Jamie, Smith, Matthew L, Ommen, Hans Beier, Overgaard, Ulrik, Dennis, Mike, Knapper, Steven, Kaur, Harpreet, Taussig, David C, Mehta, Priyanka, Raj, Kavita, Novitzky-Basso, Igor, Nikolousis, Emmanouil, Danby, Robert D, Krishnamurthy, Pramila, Hill, Kate, Finnegan, Damian, Alimam, Samah, Hurst, Erin, Johnson, Peter, Khan, Anjum Bashir, Salim, Rahuman, Craddock, Charles F, Spearing, Ruth Lilian, Gilkes, Amanda Frances, Gale, Rosemary E, Burnett, Alan Kenneth, Russell, Nigel H and Grimwade, David (2020) Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study. Blood. ISSN 1528-0020.

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Relapse remains the most common cause of treatment failure for patients with acute myeloid leukaemia (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 (FCM) prior to 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 analysed pre-transplant blood and bone marrow samples by reverse-transcription polymerase chain reaction (RT-qPCR) in 107 patients with NPM1 mutant AML enrolled in the UK National Cancer Research Institute (NCRI) AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies / 105 ABL in the PB and <1000 copies in the BM) and high levels of MRD had an estimated 2y overall survival (OS) of 83%, 63% and 13% respectively (p<0.0001). Focussing on patients with low level MRD prior to alloSCT, those with FLT3 ITD had significantly poorer outcome (hazard ratio, HR, 6.14, p=0.01). Combining these variables was highly prognostic, dividing patients into two groups with 2y OS of 17% and 82% (HR 13.2, p<0.0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y OS 56% vs 96%, HR 3.24, p=0.0005) and in MRD positive patients (2y OS 34% vs 100%, HR 3.78, p=0.003) but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (

Item Type: Article
Subjects: WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Mr Philip O'Reilly
Date Deposited: 20 Jan 2020 16:21
Last Modified: 20 Jan 2020 16:21

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