Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results

被引：58

作者：

Gardin, Claude ^{[1
]}

Pautas, Cecile ^{[2
]}

Fournier, Elise ^{[3
]}

Itzykson, Raphael ^{[4
]}

Lemasle, Emilie ^{[5
]}

Bourhis, Jean-Henri ^{[6
]}

Ades, Lionel ^{[4
]}

Marolleau, Jean-Pierre ^{[7
]}

Malfuson, Jean-Valere ^{[8
]}

Gastaud, Lauris ^{[9
]}

Raffoux, Emmanuel ^{[4
]}

Lambert, Juliette ^{[10
]}

Braun, Thorsten ^{[1
]}

Thomas, Xavier ^{[11
]}

Chantepie, Sylvain ^{[12
]}

Cluzeau, Thomas ^{[13
]}

de Botton, Stephane ^{[6
]}

Berthon, Celine ^{[14
]}

Boissel, Nicolas ^{[4
]}

Duployez, Nicolas ^{[3
]}

Terre, Christine ^{[15
]}

de Latour, Regis Peffault ^{[4
]}

Michallet, Mauricette ^{[11
]}

Celli-Lebras, Karine ^{[16
]}

Preudhomme, Claude ^{[3
]}

Dombret, Herve ^{[4
]}

机构：

[1] Univ Paris Nord, Hop Avicenne, AP HP, Dept Hematol, Bobigny, France

[2] Hop Henri Mondor, AP HP, Dept Hematol, Creteil, France

[3] Univ Lille, Ctr Hosp Univ Claude Huriez, Biol & Pathol Ctr, Dept Hematol,INSERM,UMR S 1172, Lille, France

[4] Univ Paris, Hop St Louis, AP HP, Dept Hematol,St Louis Inst Res, Paris, France

[5] Henri Becquerel Ctr, Dept Hematol, Rouen, France

[6] Inst Gustave Roussy, Dept Hematol, Villejuif, France

[7] Ctr Hosp Univ, Dept Hematol, Amiens, France

[8] Hop Percy, Dept Hematol, Clamart, France

[9] Ctr Antoine Lacassagne, Dept Hematol, Nice, France

[10] Univ Versailles St Quentin, Dept Hematol, Hop Andre Mignot, Versailles, France

[11] Ctr Leon Berard, Serv Hematol, Lyon, France

[12] Ctr Hosp Univ, Dept Hematol, Caen, France

[13] Ctr Hosp Univ, Dept Hematol, Nice, France

[14] Ctr Hosp Univ Claude Huriez, Dept Hematol, Lille, France

[15] Univ Versailles St Quentin, Lab Cytogenet, HopAndre Mignot, Versailles, France

[16] Univ Paris, Hop St Louis, AP HP,St Louis Inst, Acute Leukemia French Assoc,Off Clin Res Hematol, Paris, France

来源：

BLOOD ADVANCES | 2020年 / 4卷 / 09期

关键词：

ACUTE MYELOID-LEUKEMIA; 1ST COMPLETE REMISSION; HIGH-DOSE DAUNORUBICIN; POSTREMISSION TREATMENT; CELL TRANSPLANTATION; DIAGNOSIS; RECOMMENDATIONS; CLASSIFICATION; MANAGEMENT; CANCER;

D O I：

10.1182/bloodadvances.2019001349

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In this study, we aimed to refine prognostication of older with acute myeloid leukemia (AML) after intensive chemotherapy. Five hundred and nine patients aged 60 years or older (median age, 68 years) were prospectively enrolled in the intensive Acute Leukemia French Association (ALFA)-1200 trial between 2012 and 2016, and 471 patient samples were submitted to multigene analysis. Mutations in any of 8 genes frequently altered in myelodysplastic syndromes (MDS), including ASXL1, SRSF2, STAG2, BCOR, U2AF1, EZH2, SF3B1, and ZRSR2, defined a secondary AML (sAML)-like disease, as reported. Of the samples analyzed, 48% included sAML-like gene mutations. These mutations were associated with a shorter event-free survival, both overall (hazard ratio, 1.46; 95% confidence interval, 1.19-1.79; P < .001) and within the European LeukemiaNet (ELN)-2017 intermediate-risk subgroup (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28; P = .044), which excludes ASXL1-mutated cases by definition. We therefore included patients with intermediate-risk AML carrying sAML-like mutations in a single high-risk patients group together with adverse-risk patients with AML, whereas other intermediate-risk patients were included in a standard-risk group together with favorable-risk patients (high-risk/standard-risk patient ratio, 1.00). Using this 2-class risk assessment, we observed that transplantation prolonged overall survival from remission in patients with high-risk AML only, not in patients with standard-risk AML. Routine analysis of sAML-like gene mutations may thus improve the definition of high-risk older patients with AML, and better identify the half of older patients who clearly derive survival benefit from allogeneic transplantation in first remission.

引用

页码：1942 / 1949

页数：8