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

被引：94

作者：

Angenendt, Linus ^{[1
]}

Roellig, Christoph ^{[2
]}

Montesinos, Pau ^{[3
,4
]}

Martinez-Cuadron, David ^{[3
,4
]}

Barragan, Eva ^{[3
,4
]}

Garcia, Raimundo ^{[5
]}

Botella, Carmen ^{[6
]}

Martinez, Pilar ^{[7
]}

Ravandi, Farhad ^{[8
]}

Kadia, Tapan ^{[8
]}

Kantarjian, Hagop M. ^{[8
]}

Cortes, Jorge ^{[8
]}

Juliusson, Gunnar ^{[9
]}

Lazarevic, Vladimir ^{[9
]}

Hoglund, Martin ^{[10
]}

Lehmann, Soren ^{[10
]}

Recher, Christian ^{[11
]}

Pigneux, Arnaud ^{[12
]}

Bertoli, Sarah ^{[11
]}

Dumas, Pierre-Yves ^{[12
]}

Dombret, Herve ^{[13
]}

Preudhomme, Claude ^{[14
]}

Micol, Jean-Baptiste ^{[15
]}

Terre, Christine ^{[16
]}

Racil, Zdenek ^{[17
]}

Novak, Jan ^{[18
]}

Zak, Pavel ^{[19
]}

Wei, Andrew H. ^{[20
]}

Tiong, Ing S. ^{[20
]}

Wall, Meaghan ^{[21
]}

Estey, Elihu ^{[22
]}

Shaw, Carole ^{[22
]}

Exeler, Rita ^{[23
]}

Wagenfuehr, Lisa ^{[2
]}

Stoelzel, Friedrich ^{[2
]}

Thiede, Christian ^{[2
]}

Stelljes, Matthias ^{[1
]}

Lenz, Georg ^{[1
]}

Mikesch, Jan-Henrik ^{[1
]}

Serve, Hubert ^{[24
]}

Ehninger, Gerhard ^{[2
]}

Berdel, Wolfgang E. ^{[1
]}

Kramer, Michael ^{[2
]}

Krug, Utz ^{[25
]}

Schliemann, Christoph ^{[1
]}

机构：

[1] Univ Hosp Munster, Munster, Germany

[2] Tech Univ Dresden, Univ Hosp, Dresden, Germany

[3] Hosp Univ & Politec La Fe, Valencia, Spain

[4] Ctr Invest Biomed Red Canc, Madrid, Spain

[5] Gen Hosp Castellon, Castellon de La Plana, Spain

[6] Hosp Gen Alicante, Alicante, Spain

[7] Hosp 12 Octubre, Madrid, Spain

[8] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[9] Lund Univ, Lund, Sweden

[10] Uppsala Univ, Uppsala Univ Hosp, Uppsala, Sweden

[11] CHU Toulouse, Toulouse, France

[12] CHU Bordeaux, Hop Haut Leveque, Bordeaux, France

[13] Paris Diderot Univ, Paris, France

[14] Inst Natl Sante & Rech Med Lille, Lille, France

[15] Paris Saclay Univ, Gustave Roussy, Villejuif, France

[16] Ctr Transfus Sanguine, Le Chesnay, France

[17] Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic

[18] Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Prague, Czech Republic

[19] Charles Univ Prague, Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic

[20] Monash Univ, Alfred Hosp, Melbourne, Vic, Australia

[21] St Vincents Hosp, Melbourne, Vic, Australia

[22] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA

[23] Univ Munster, Munster, Germany

[24] Univ Hosp Frankfurt, Frankfurt, Germany

[25] Klinikum Leverkusen, Leverkusen, Germany

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 29期

基金：

英国医学研究理事会;

关键词：

ACUTE MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; NPM1; MUTATIONS; ADULT PATIENTS; AML; NUCLEOPHOSMIN; IMPACT; TRANSPLANTATION;

D O I：

10.1200/JCO.19.00416

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSENucleophosmin 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.METHODSWe analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.RESULTSAmong 2,426 patients with NPM1(mut)/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 NPM1(mut)/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.CONCLUSIONKaryotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) 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 NPM1(mut)/FLT3-ITDneg/low AML.

引用

页码：2632 / +

页数：13

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