TY - JOUR
T1 - Molecular MRD status and outcome after transplantation in NPM1-mutated AML
AU - Dillon, Richard
AU - Hills, Robert K
AU - Freeman, Sylvie D
AU - Potter, Nicola
AU - Jovanovic, Jelena
AU - Ivey, Adam
AU - Kanda, Anju Shankar
AU - Runglall, Manohursingh
AU - Foot, Nicola
AU - Valganon, Mikel
AU - Khwaja, Asim
AU - Cavenagh, Jamie
AU - Smith, Matthew L
AU - Ommen, Hans Beier
AU - Overgaard, Ulrik
AU - Dennis, Mike
AU - Knapper, Steven
AU - Kaur, Harpreet
AU - Taussig, David C
AU - Mehta, Priyanka
AU - Raj, Kavita
AU - Novitzky-Basso, Igor
AU - Nikolousis, Emmanouil
AU - Danby, Robert D
AU - Krishnamurthy, Pramila
AU - Hill, Kate
AU - Finnegan, Damian
AU - Alimam, Samah
AU - Hurst, Erin
AU - Johnson, Peter
AU - Khan, Anjum Bashir
AU - Salim, Rahuman
AU - Craddock, Charles F
AU - Ruth Lilian Spearing, Dr
AU - Gilkes, Amanda Frances
AU - Gale, Rosemary E
AU - Alan Kenneth Burnett, -
AU - Russell, Nigel H.
AU - Grimwade, David
N1 - © 2020 by The American Society of Hematology.
PY - 2020/2/27
Y1 - 2020/2/27
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=85080836908&partnerID=8YFLogxK
U2 - 10.1182/blood.2019002959
DO - 10.1182/blood.2019002959
M3 - Article
C2 - 31932839
SN - 0006-4971
VL - 135
SP - 680
EP - 688
JO - Blood
JF - Blood
IS - 9
ER -