Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F22%3A00126253" target="_blank" >RIV/00216224:14110/22:00126253 - isvavai.cz</a>

Výsledek na webu

<a href="https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01267-7" target="_blank" >https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01267-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13045-022-01267-7" target="_blank" >10.1186/s13045-022-01267-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations

Popis výsledku v původním jazyce

Background Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed. Methods We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM. Results AML patients with EM presented with significantly higher counts of white blood cells (p &lt; 0.0001), peripheral blood blasts (p &lt; 0.0001), bone marrow blasts (p = 0.019), and LDH (p &lt; 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p &lt; 0.001), FLT3-ITD (OR: 1.72, p &lt; 0.001) and PTPN11 (OR: 2.46, p &lt; 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p &lt; 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p &lt; 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively). Conclusion Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.

Název v anglickém jazyce

Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations

Popis výsledku anglicky

Background Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed. Methods We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM. Results AML patients with EM presented with significantly higher counts of white blood cells (p &lt; 0.0001), peripheral blood blasts (p &lt; 0.0001), bone marrow blasts (p = 0.019), and LDH (p &lt; 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p &lt; 0.001), FLT3-ITD (OR: 1.72, p &lt; 0.001) and PTPN11 (OR: 2.46, p &lt; 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p &lt; 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p &lt; 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively). Conclusion Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

JOURNAL OF HEMATOLOGY & ONCOLOGY

ISSN

1756-8722

e-ISSN

1756-8722

Svazek periodika

15

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

1-13

Kód UT WoS článku

000795132900001

EID výsledku v databázi Scopus

2-s2.0-85130011025