Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts

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Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia : A Pooled Analysis of Individual Patient Data From Nine International Cohorts. / Angenendt, Linus; Röllig, Christoph; Montesinos, Pau; Martínez-Cuadrón, David; Barragan, Eva; García, Raimundo; Botella, Carmen; Martínez, Pilar; Ravandi, Farhad; Kadia, Tapan; Kantarjian, Hagop M.; Cortes, Jorge; Juliusson, Gunnar; Lazarevic, Vladimir; Recher, Christian; Pigneux, Arnaud; Bertoli, Sarah; Dumas, Pierre Yves; Dombret, Hervé; Preudhomme, Claude; Micol, Jean Baptiste; Terré, Christine; Ráčil, Zdeněk; Novák, Jan; Žák, Pavel; Wei, Andrew H.; Tiong, Ing S.; Wall, Meaghan; Estey, Elihu; Shaw, Carole; Exeler, Rita; Wagenführ, Lisa; Stölzel, Friedrich; Thiede, Christian; Stelljes, Matthias; Lenz, Georg; Mikesch, Jan Henrik; Serve, Hubert; Ehninger, Gerhard; Berdel, Wolfgang E.; Kramer, Michael; Krug, Utz; Schliemann, Christoph.

I: Journal of Clinical Oncology, Vol. 37, Nr. 29, 10.10.2019, s. 2632-2642.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Angenendt, L, Röllig, C, Montesinos, P, Martínez-Cuadrón, D, Barragan, E, García, R, Botella, C, Martínez, P, Ravandi, F, Kadia, T, Kantarjian, HM, Cortes, J, Juliusson, G, Lazarevic, V, Recher, C, Pigneux, A, Bertoli, S, Dumas, PY, Dombret, H, Preudhomme, C, Micol, JB, Terré, C, Ráčil, Z, Novák, J, Žák, P, Wei, AH, Tiong, IS, Wall, M, Estey, E, Shaw, C, Exeler, R, Wagenführ, L, Stölzel, F, Thiede, C, Stelljes, M, Lenz, G, Mikesch, JH, Serve, H, Ehninger, G, Berdel, WE, Kramer, M, Krug, U & Schliemann, C 2019, 'Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts', Journal of Clinical Oncology, vol. 37, nr. 29, s. 2632-2642. https://doi.org/10.1200/JCO.19.00416

APA

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Angenendt L, Röllig C, Montesinos P, Martínez-Cuadrón D, Barragan E, García R, Botella C, Martínez P, Ravandi F, Kadia T, Kantarjian HM, Cortes J, Juliusson G, Lazarevic V, Recher C, Pigneux A, Bertoli S, Dumas PY, Dombret H, Preudhomme C, Micol JB, Terré C, Ráčil Z, Novák J, Žák P, Wei AH, Tiong IS, Wall M, Estey E, Shaw C, Exeler R, Wagenführ L, Stölzel F, Thiede C, Stelljes M, Lenz G, Mikesch JH, Serve H, Ehninger G, Berdel WE, Kramer M, Krug U, Schliemann C. 2019. Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts. Journal of Clinical Oncology. 37(29):2632-2642. https://doi.org/10.1200/JCO.19.00416

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Angenendt, Linus ; Röllig, Christoph ; Montesinos, Pau ; Martínez-Cuadrón, David ; Barragan, Eva ; García, Raimundo ; Botella, Carmen ; Martínez, Pilar ; Ravandi, Farhad ; Kadia, Tapan ; Kantarjian, Hagop M. ; Cortes, Jorge ; Juliusson, Gunnar ; Lazarevic, Vladimir ; Recher, Christian ; Pigneux, Arnaud ; Bertoli, Sarah ; Dumas, Pierre Yves ; Dombret, Hervé ; Preudhomme, Claude ; Micol, Jean Baptiste ; Terré, Christine ; Ráčil, Zdeněk ; Novák, Jan ; Žák, Pavel ; Wei, Andrew H. ; Tiong, Ing S. ; Wall, Meaghan ; Estey, Elihu ; Shaw, Carole ; Exeler, Rita ; Wagenführ, Lisa ; Stölzel, Friedrich ; Thiede, Christian ; Stelljes, Matthias ; Lenz, Georg ; Mikesch, Jan Henrik ; Serve, Hubert ; Ehninger, Gerhard ; Berdel, Wolfgang E. ; Kramer, Michael ; Krug, Utz ; Schliemann, Christoph. / Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia : A Pooled Analysis of Individual Patient Data From Nine International Cohorts. I: Journal of Clinical Oncology. 2019 ; Vol. 37, Nr. 29. s. 2632-2642.

RIS

TY - JOUR

T1 - Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia

T2 - A Pooled Analysis of Individual Patient Data From Nine International Cohorts

AU - Angenendt, Linus

AU - Röllig, Christoph

AU - Montesinos, Pau

AU - Martínez-Cuadrón, David

AU - Barragan, Eva

AU - García, Raimundo

AU - Botella, Carmen

AU - Martínez, Pilar

AU - Ravandi, Farhad

AU - Kadia, Tapan

AU - Kantarjian, Hagop M.

AU - Cortes, Jorge

AU - Juliusson, Gunnar

AU - Lazarevic, Vladimir

AU - Recher, Christian

AU - Pigneux, Arnaud

AU - Bertoli, Sarah

AU - Dumas, Pierre Yves

AU - Dombret, Hervé

AU - Preudhomme, Claude

AU - Micol, Jean Baptiste

AU - Terré, Christine

AU - Ráčil, Zdeněk

AU - Novák, Jan

AU - Žák, Pavel

AU - Wei, Andrew H.

AU - Tiong, Ing S.

AU - Wall, Meaghan

AU - Estey, Elihu

AU - Shaw, Carole

AU - Exeler, Rita

AU - Wagenführ, Lisa

AU - Stölzel, Friedrich

AU - Thiede, Christian

AU - Stelljes, Matthias

AU - Lenz, Georg

AU - Mikesch, Jan Henrik

AU - Serve, Hubert

AU - Ehninger, Gerhard

AU - Berdel, Wolfgang E.

AU - Kramer, Michael

AU - Krug, Utz

AU - Schliemann, Christoph

PY - 2019/10/10

Y1 - 2019/10/10

N2 - PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption. METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1mut/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers. RESULTS: Among 2,426 patients with NPM1mut/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1mut/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome. CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1mut/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1mut share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1mut/FLT3-ITDneg/low AML.

AB - PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption. METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1mut/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers. RESULTS: Among 2,426 patients with NPM1mut/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1mut/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome. CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1mut/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1mut share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1mut/FLT3-ITDneg/low AML.

U2 - 10.1200/JCO.19.00416

DO - 10.1200/JCO.19.00416

M3 - Article

VL - 37

SP - 2632

EP - 2642

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 29

ER -