Molecular MRD status and outcome after transplantation in NPM1-mutated AML

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  • Richard Dillon, King's College London, Guy's and St Thomas' NHS Foundation Trust, Department of Haematology
  • ,
  • Robert Hills, University of Oxford, Oxford
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  • Sylvie Freeman, Birmingham University
  • ,
  • Nicola Potter, King's College London, Guy's and St Thomas' NHS Foundation Trust
  • ,
  • Jelena Jovanovic, King's College London
  • ,
  • Adam Ivey, King's College London
  • ,
  • Anju Shankar Kanda, King's College London
  • ,
  • Manohursingh Runglall, King's College London
  • ,
  • Nicola Foot, Guy's and St Thomas' NHS Foundation Trust
  • ,
  • Mikel Valganon, Guy's and St Thomas' NHS Foundation Trust
  • ,
  • Asim Khwaja, University College London
  • ,
  • Jamie Cavenagh, St. Bartholomew's Hospital
  • ,
  • Matthew Smith, St. Bartholomew's Hospital
  • ,
  • Hans Beier Ommen
  • Ulrik Malthe Overgaard, Rigshospitalet
  • ,
  • Mike Dennis, The Christie Hospital
  • ,
  • Steven Knapper, Cardiff University
  • ,
  • Harpreet Kaur, Royal Hallamshire Hospital
  • ,
  • David Taussig, Royal Marsden Hospital, Sutton
  • ,
  • Priyanka Mehta, University Hospitals Bristol NHS Foundation Trust
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  • Kavita Raj, Department of Haematology
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  • Igor Novitzky-Basso, University of Glasgow
  • ,
  • Emmanouil Nikolousis, Birmingham Heartlands Hospital
  • ,
  • Robert Danby, Oxford University Hospitals NHS Foundation Trust
  • ,
  • Pramila Krishnamurthy, Cambridge University Hospitals NHS Foundation Trust
  • ,
  • Kate Hill, Southampton University Hospital NHS Foundation Trust
  • ,
  • Damian Finnegan, Belfast Health and Social Care Trust
  • ,
  • Samah Alimam, King's College London, Department of Haematology
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  • Erin Hurst, Royal Victoria Infirmary
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  • Peter Johnson, NHS Lothian
  • ,
  • Anjum Khan, St James's University Hospital
  • ,
  • Rahuman Salim, Clatterbridge Cancer Centre
  • ,
  • Charles Craddock, University Hospitals Birmingham NHS Foundation Trust
  • ,
  • Ruth Spearing, Christchurch Hospital New Zealand
  • ,
  • Amanda Gilkes, Cardiff University
  • ,
  • Rosemary Gale, University College London
  • ,
  • Alan Burnett, United Kingdom
  • ,
  • Nigel H. Russell, Department of Haematology, Nottingham University Hospitals NHS Trust
  • ,
  • David Grimwade, King's College London, Department of Haematology

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).

OriginalsprogEngelsk
TidsskriftBlood
Vol/bind135
Nummer9
Sider (fra-til)680-688
Antal sider9
ISSN0006-4971
DOI
StatusUdgivet - 2020

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