Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy

被引：235

作者：

Pratcorona, Marta ^{[1
]}

Brunet, Salut ^{[2
]}

Nomdedeu, Josep ^{[2
]}

Maria Ribera, Josep ^{[3
]}

Tormo, Mar ^{[4
]}

Duarte, Rafael ^{[5
]}

Escoda, Lourdes ^{[6
]}

Guardia, Ramon ^{[7
]}

Queipo de Llano, M. Paz ^{[8
]}

Salamero, Olga ^{[9
]}

Bargay, Joan ^{[10
]}

Pedro, Carmen ^{[11
]}

Maria Marti, Josep ^{[12
]}

Torrebadell, Montserrat ^{[1
]}

Diaz-Beya, Marina ^{[1
]}

Camos, Mireia ^{[13
]}

Colomer, Dolors ^{[1
]}

Hoyos, Montserrat ^{[2
]}

Sierra, Jorge ^{[2
]}

Esteve, Jordi ^{[1
]}

机构：

[1] Hosp Clin Barcelona, Dept Hematol, Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Spain

[2] Univ Autonoma Barcelona, Dept Hematol, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain

[3] Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Dept Hematol, Badalona, Spain

[4] Hosp Clin, Dept Hematol, Valencia, Spain

[5] Hosp Duran & Reynals, Dept Hematol, Lhospitalet De Llobregat, Spain

[6] Hosp Joan 23, Dept Hematol, Tarragona, Spain

[7] Hosp Josep Trueta, Dept Hematol, Girona, Spain

[8] Hosp Virgen de la Victoria, Dept Hematol, Malaga, Spain

[9] Hosp Valle De Hebron, Dept Hematol, Barcelona, Spain

[10] Hosp Son Llatzer, Dept Hematol, Palma De Mallorca, Spain

[11] Hosp del Mar, Dept Hematol, Barcelona, Spain

[12] Hosp Mutua de Terrassa, Dept Hematol, Terrassa, Spain

[13] Hosp St Joan de Deu, Dept Hematol, Esplugas de Llobregat, Spain

来源：

BLOOD | 2013年 / 121卷 / 14期

关键词：

INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; PROGNOSTIC IMPACT; DNMT3A MUTATIONS; GENE-MUTATIONS; ADULT PATIENTS; AML; LEVEL; PREVALENCE;

D O I：

10.1182/blood-2012-06-431122

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (>= 0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio. (Blood. 2013;121(14):2734-2738)

引用

页码：2734 / 2738

页数：5

共 25 条

[1] FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group [J].

Abu-Duhier, FM ;

Goodeve, AC ;

Wilson, GA ;

Gari, MA ;

Peake, IR ;

Rees, DC ;

Vandenberghe, EA ;

Winship, PR ;

Reilly, JT .

BRITISH JOURNAL OF HAEMATOLOGY, 2000, 111 (01) :190-195

[2] Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype [J].

Boissel, N ;

Renneville, A ;

Biggio, V ;

Philippe, N ;

Thomas, X ;

Cayuela, JM ;

Terre, C ;

Tigaud, I ;

Castaigne, S ;

Raffoux, E ;

De Botton, S ;

Fenaux, P ;

Dombret, H ;

Preudhomme, C .

BLOOD, 2005, 106 (10) :3618-3620

[3] Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML [J].

Bornhaeuser, Martin ;

Illmer, Thomas ;

Schaich, Markus ;

Soucek, Silke ;

Ehninger, Gerhard ;

Thiede, Christian .

BLOOD, 2007, 109 (05) :2264-2265

[4] Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis [J].

Brunet, Salut ;

Labopin, Myriam ;

Esteve, Jordi ;

Cornelissen, Jan ;

Socie, Gerard ;

Iori, Anna P. ;

Verdonck, Leo F. ;

Volin, Liisa ;

Gratwohl, Alois ;

Sierra, Jorge ;

Mohty, Mohamad ;

Rocha, Vanderson .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (07) :735-741

[5] Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD [J].

de Jonge, Hendrik J. M. ;

Valk, Peter J. M. ;

de Bont, Eveline S. J. M. ;

Schuringa, Jan Jacob ;

Ossenkoppele, Gert ;

Vellenga, Edo ;

Huls, Gerwin .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2011, 96 (09) :1310-1317

[6] Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics:: interaction with other gene mutations [J].

Döhner, K ;

Schlenk, RF ;

Habdank, M ;

Scholl, C ;

Rücker, FG ;

Corbacioglu, A ;

Bullinger, L ;

Fröhling, S ;

Döhner, H .

BLOOD, 2005, 106 (12) :3740-3746

[7] Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group [J].

Gaidzik, Verena Ingeborg ;

Schlenk, Richard Friedrich ;

Moschny, Simone ;

Becker, Annegret ;

Bullinger, Lars ;

Corbacioglu, Andrea ;

Krauter, Juergen ;

Schlegelberger, Brigitte ;

Ganser, Arnold ;

Doehner, Hartmut ;

Doehner, Konstanze .

BLOOD, 2009, 113 (19) :4505-4511

[8] No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML 10 and 12 trials [J].

Gale, RE ;

Hills, R ;

Kottaridis, PD ;

Srirangan, S ;

Wheatley, K ;

Burnett, AK ;

Linch, DC .

BLOOD, 2005, 106 (10) :3658-3665

[9] The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia [J].

Gale, Rosemary E. ;

Green, Claire ;

Allen, Christopher ;

Mead, Adam J. ;

Burnett, Alan K. ;

Hils, Robert K. ;

Linch, David C. .

BLOOD, 2008, 111 (05) :2776-2784

[10] Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials [J].

Grimwade, David ;

Hills, Robert K. ;

Moorman, Anthony V. ;

Walker, Helen ;

Chatters, Stephen ;

Goldstone, Anthony H. ;

Wheatley, Keith ;

Harrison, Christine J. ;

Burnett, Alan K. .

BLOOD, 2010, 116 (03) :354-365

← 1 2 3 →