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

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Molecular MRD status and outcome after transplantation in NPM1-mutated AML. / 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; Ruth Lilian Spearing, Dr; Gilkes, Amanda Frances; Gale, Rosemary E; Alan Kenneth Burnett, -; Russell, Nigel H.; Grimwade, David.

In: Blood, Vol. 135, No. 9, 27.02.2020, p. 680-688.

Research output: Contribution to journalArticlepeer-review

Harvard

Dillon, R, Hills, RK, Freeman, SD, Potter, N, Jovanovic, J, Ivey, A, Kanda, AS, Runglall, M, Foot, N, Valganon, M, Khwaja, A, Cavenagh, J, Smith, ML, Ommen, HB, Overgaard, U, Dennis, M, Knapper, S, Kaur, H, Taussig, DC, Mehta, P, Raj, K, Novitzky-Basso, I, Nikolousis, E, Danby, RD, Krishnamurthy, P, Hill, K, Finnegan, D, Alimam, S, Hurst, E, Johnson, P, Khan, AB, Salim, R, Craddock, CF, Ruth Lilian Spearing, D, Gilkes, AF, Gale, RE, Alan Kenneth Burnett, Russell, NH & Grimwade, D 2020, 'Molecular MRD status and outcome after transplantation in NPM1-mutated AML', Blood, vol. 135, no. 9, pp. 680-688. https://doi.org/10.1182/blood.2019002959

APA

Dillon, R., Hills, R. K., Freeman, S. D., Potter, N., Jovanovic, J., Ivey, A., Kanda, A. S., Runglall, M., Foot, N., Valganon, M., Khwaja, A., Cavenagh, J., Smith, M. L., Ommen, H. B., Overgaard, U., Dennis, M., Knapper, S., Kaur, H., Taussig, D. C., ... Grimwade, D. (2020). Molecular MRD status and outcome after transplantation in NPM1-mutated AML. Blood, 135(9), 680-688. https://doi.org/10.1182/blood.2019002959

Vancouver

Author

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 ; Ruth Lilian Spearing, Dr ; Gilkes, Amanda Frances ; Gale, Rosemary E ; Alan Kenneth Burnett, - ; Russell, Nigel H. ; Grimwade, David. / Molecular MRD status and outcome after transplantation in NPM1-mutated AML. In: Blood. 2020 ; Vol. 135, No. 9. pp. 680-688.

Bibtex

@article{1c578f895bef4e25ae3bdc357b5edc33,
title = "Molecular MRD status and outcome after transplantation in NPM1-mutated AML",
abstract = "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).",
author = "Richard Dillon and Hills, {Robert K} and Freeman, {Sylvie D} and Nicola Potter and Jelena Jovanovic and Adam Ivey and Kanda, {Anju Shankar} and Manohursingh Runglall and Nicola Foot and Mikel Valganon and Asim Khwaja and Jamie Cavenagh and Smith, {Matthew L} and Ommen, {Hans Beier} and Ulrik Overgaard and Mike Dennis and Steven Knapper and Harpreet Kaur and Taussig, {David C} and Priyanka Mehta and Kavita Raj and Igor Novitzky-Basso and Emmanouil Nikolousis and Danby, {Robert D} and Pramila Krishnamurthy and Kate Hill and Damian Finnegan and Samah Alimam and Erin Hurst and Peter Johnson and Khan, {Anjum Bashir} and Rahuman Salim and Craddock, {Charles F} and {Ruth Lilian Spearing}, Dr and Gilkes, {Amanda Frances} and Gale, {Rosemary E} and {Alan Kenneth Burnett}, - and Russell, {Nigel H.} and David Grimwade",
note = "{\textcopyright} 2020 by The American Society of Hematology.",
year = "2020",
month = feb,
day = "27",
doi = "10.1182/blood.2019002959",
language = "English",
volume = "135",
pages = "680--688",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

RIS

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

VL - 135

SP - 680

EP - 688

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -