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

Autor:	Dillon R; Department of Medical and Molecular Genetics, King's College, London, United Kingdom.; Cancer Genetics Service, Viapath, Guy's Hospital, London, United Kingdom.; Department of Haematology, Guy's Hospital, London, United Kingdom., Hills R; Nuffield Department of Population Health, University of Oxford, United Kingdom., Freeman S; Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom., Potter N; Department of Medical and Molecular Genetics, King's College, London, United Kingdom.; Cancer Genetics Service, Viapath, Guy's Hospital, London, United Kingdom., Jovanovic J; Department of Medical and Molecular Genetics, King's College, London, United Kingdom., Ivey A; Department of Medical and Molecular Genetics, King's College, London, United Kingdom., Kanda AS; Department of Medical and Molecular Genetics, King's College, London, United Kingdom., Runglall M; Department of Medical and Molecular Genetics, King's College, London, United Kingdom., Foot N; Cancer Genetics Service, Viapath, Guy's Hospital, London, United Kingdom., Valganon M; Cancer Genetics Service, Viapath, Guy's Hospital, London, United Kingdom., Khwaja A; Department of Haematology, University College, London, United Kingdom., Cavenagh J; Bart's Hospital, London, United Kingdom., Smith M; Bart's Hospital, London, United Kingdom., Ommen HB; University Hospital, Aarhus, Denmark., Overgaard UM; Rigshospitalet, Copenhagen, Denmark., Dennis M; Christie Hospital, Manchester, United Kingdom., Knapper S; Department of Haematology, Cardiff University, Cardiff, United Kingdom., Kaur H; Royal Hallamshire Hospital, Sheffield, United Kingdom., Taussig D; Royal Marsden Hospital, Sutton, United Kingdom., Mehta P; Bristol Haematology and Oncology Centre, Bristol, United Kingdom., Raj K; Department of Haematology, Guy's Hospital, London, United Kingdom., Novitzky-Basso I; Beatson Cancer Centre, Glasgow, United Kingdom., Nikolousis E; Heartlands Hospital, Birmingham, United Kingdom., Danby R; Churchill Hospital, Oxford, United Kingdom., Krishnamurthy P; Addenbrooke's Hospital, Cambridge, United Kingdom., Hill K; University Hospital, Southampton, United Kingdom., Finnegan D; Belfast City Hospital, Belfast, United Kingdom., Alimam S; Department of Medical and Molecular Genetics, King's College, London, United Kingdom.; Department of Haematology, Guy's Hospital, London, United Kingdom., Hurst E; Royal Victoria Infirmary, Newcastle, United Kingdom., Johnson P; Western General Hospital, Edinburgh, United Kingdom., Khan A; St James' Hospital, Leeds, United Kingdom., Salim R; Clatterbridge Cancer Centre, Liverpool, United Kingdom., Craddock C; Queen Elizabeth Hospital, Birmingham, United Kingdom., Spearing R; Christchurch Hospital, Christchurch, New Zealand., Gilkes A; Department of Haematology, Cardiff University, Cardiff, United Kingdom., Gale R; Department of Haematology, University College, London, United Kingdom., Burnett A; Blackwaterfoot, Isle of Arran, United Kingdom; and., Russell NH; Department of Haematology, Guy's Hospital, London, United Kingdom.; Nottingham University Hospital, Nottingham, United Kingdom., Grimwade D; Department of Medical and Molecular Genetics, King's College, London, United Kingdom.; Department of Haematology, Guy's Hospital, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2020 Feb 27; Vol. 135 (9), pp. 680-688.
DOI:	10.1182/blood.2019002959
Abstrakt:	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). (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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