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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F19%3A10399680" target="_blank" >RIV/00179906:_____/19:10399680 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/19:00112133 RIV/00216208:11120/19:43918525 RIV/00216208:11150/19:10399680 RIV/65269705:_____/19:00071280

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=hvxVB1-qW5" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=hvxVB1-qW5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1200/JCO.19.00416" target="_blank" >10.1200/JCO.19.00416</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 &lt; .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P &lt; .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P &lt; .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 &lt; .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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 &lt; .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P &lt; .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P &lt; .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 &lt; .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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/NV15-25809A" target="_blank" >NV15-25809A: Národní program studia mutací a klonality leukemických buněk u pacientů s akutní myeloidní leukémií</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Clinical Oncology

ISSN

0732-183X

e-ISSN

—

Svazek periodika

37

Číslo periodika v rámci svazku

29

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

2632-2642

Kód UT WoS článku

000491485600006

EID výsledku v databázi Scopus

2-s2.0-85072994068