Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

L. Angenendt, C. Röllig, P. Montesinos, D. Martínez-Cuadrón, E. Barragan, R. García, C. Botella, P. Martínez, F. Ravandi, T. Kadia, HM. Kantarjian, J. Cortes, G. Juliusson, V. Lazarevic, M. Höglund, S. Lehmann, C. Recher, A. Pigneux, S. Bertoli,...

. 2019 ; 37 (29) : 2632-2642. [pub] 20190820

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20023595

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20023595
003      
CZ-PrNML
005      
20240418104741.0
007      
ta
008      
201125s2019 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1200/JCO.19.00416 $2 doi
035    __
$a (PubMed)31430225
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Angenendt, Linus $u University Hospital Münster, Münster, Germany.
245    10
$a Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts / $c L. Angenendt, C. Röllig, P. Montesinos, D. Martínez-Cuadrón, E. Barragan, R. García, C. Botella, P. Martínez, F. Ravandi, T. Kadia, HM. Kantarjian, J. Cortes, G. Juliusson, V. Lazarevic, M. Höglund, S. Lehmann, C. Recher, A. Pigneux, S. Bertoli, PY. Dumas, H. Dombret, C. Preudhomme, JB. Micol, C. Terré, Z. Ráčil, J. Novák, P. Žák, AH. Wei, IS. Tiong, M. Wall, E. Estey, C. Shaw, R. Exeler, L. Wagenführ, F. Stölzel, C. Thiede, M. Stelljes, G. Lenz, JH. Mikesch, H. Serve, G. Ehninger, WE. Berdel, M. Kramer, U. Krug, C. Schliemann,
520    9_
$a 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.
650    _2
$a mladiství $7 D000293
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a chromozomální aberace $7 D002869
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a akutní myeloidní leukemie $x genetika $7 D015470
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a mutace $7 D009154
650    _2
$a jaderné proteiny $x genetika $7 D009687
650    _2
$a prognóza $7 D011379
650    _2
$a mladý dospělý $7 D055815
650    _2
$a tyrosinkinasa 3 podobná fms $x genetika $7 D051941
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Röllig, Christoph $u University Hospital of the Technical University Dresden, Dresden, Germany.
700    1_
$a Montesinos, Pau $u Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
700    1_
$a Martínez-Cuadrón, David $u Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
700    1_
$a Barragan, Eva $u Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
700    1_
$a García, Raimundo $u General Hospital Castellón, Castellón, Spain.
700    1_
$a Botella, Carmen $u Hospital General de Alicante, Alicante, Spain.
700    1_
$a Martínez, Pilar $u Hospital 12 de Octubre, Madrid, Spain.
700    1_
$a Ravandi, Farhad $u University of Texas MD Anderson Cancer Center, Houston, TX.
700    1_
$a Kadia, Tapan $u University of Texas MD Anderson Cancer Center, Houston, TX.
700    1_
$a Kantarjian, Hagop M $u University of Texas MD Anderson Cancer Center, Houston, TX.
700    1_
$a Cortes, Jorge $u University of Texas MD Anderson Cancer Center, Houston, TX.
700    1_
$a Juliusson, Gunnar $u Lund University, Lund, Sweden.
700    1_
$a Lazarevic, Vladimir $u Lund University, Lund, Sweden.
700    1_
$a Höglund, Martin $u Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
700    1_
$a Lehmann, Sören $u Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
700    1_
$a Recher, Christian $u Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
700    1_
$a Pigneux, Arnaud $u Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Bordeaux, France.
700    1_
$a Bertoli, Sarah $u Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
700    1_
$a Dumas, Pierre-Yves $u Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Bordeaux, France.
700    1_
$a Dombret, Hervé $u Paris Diderot University, Paris, France. $7 xx0316388
700    1_
$a Preudhomme, Claude $u Institut National de la Santé et de la Recherche Médicale Lille, Lille, France.
700    1_
$a Micol, Jean-Baptiste $u Gustave Roussy, Paris-Saclay University, Villejuif, France.
700    1_
$a Terré, Christine $u Centre de transfusion sanguine, Le Chesnay, France.
700    1_
$a Ráčil, Zdeněk $u Masaryk University, University Hospital Brno, Brno, Czech Republic.
700    1_
$a Novák, Jan $u University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Žák, Pavel $u University Hospital Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
700    1_
$a Wei, Andrew H $u The Alfred Hospital, Monash University, Melbourne, Australia.
700    1_
$a Tiong, Ing S $u The Alfred Hospital, Monash University, Melbourne, Australia.
700    1_
$a Wall, Meaghan $u St Vincent's Hospital, Melbourne, Australia.
700    1_
$a Estey, Elihu $u University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA.
700    1_
$a Shaw, Carole $u University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA.
700    1_
$a Exeler, Rita $u University of Münster, Münster, Germany.
700    1_
$a Wagenführ, Lisa $u University Hospital of the Technical University Dresden, Dresden, Germany.
700    1_
$a Stölzel, Friedrich $u University Hospital of the Technical University Dresden, Dresden, Germany.
700    1_
$a Thiede, Christian $u University Hospital of the Technical University Dresden, Dresden, Germany.
700    1_
$a Stelljes, Matthias $u University Hospital Münster, Münster, Germany.
700    1_
$a Lenz, Georg $u University Hospital Münster, Münster, Germany.
700    1_
$a Mikesch, Jan-Henrik $u University Hospital Münster, Münster, Germany.
700    1_
$a Serve, Hubert $u University Hospital Frankfurt, Frankfurt, Germany.
700    1_
$a Ehninger, Gerhard $u University Hospital of the Technical University Dresden, Dresden, Germany.
700    1_
$a Berdel, Wolfgang E $u University Hospital Münster, Münster, Germany.
700    1_
$a Kramer, Michael $u University Hospital of the Technical University Dresden, Dresden, Germany.
700    1_
$a Krug, Utz $u Klinikum Leverkusen, Leverkusen, Germany.
700    1_
$a Schliemann, Christoph $u University Hospital Münster, Münster, Germany.
773    0_
$w MED00002596 $t Journal of clinical oncology $x 1527-7755 $g Roč. 37, č. 29 (2019), s. 2632-2642
856    41
$u https://pubmed.ncbi.nlm.nih.gov/31430225 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20201125 $b ABA008
991    __
$a 20240418104735 $b ABA008
999    __
$a ok $b bmc $g 1595914 $s 1114271
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 37 $c 29 $d 2632-2642 $e 20190820 $i 1527-7755 $m Journal of clinical oncology $n J. clin. Oncol. $x MED00002596
LZP    __
$a Pubmed-20201125

Find record

Citation metrics

Archiving options