Impact of FLT3ITD mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia

被引:102
作者
Linch, David C. [1 ]
Hills, Robert K. [2 ]
Burnett, Alan K. [2 ]
Khwaja, Asim [1 ]
Gale, Rosemary E. [1 ]
机构
[1] UCL Canc Inst, Dept Haematol, London WC1E 6DD, England
[2] Cardiff Univ, Sch Med, Dept Haematol, Cardiff CF10 3AX, S Glam, Wales
基金
英国医学研究理事会;
关键词
INTERNAL TANDEM DUPLICATION; PROGNOSTIC IMPACT; POOR-PROGNOSIS; MUTATIONS; FLT3; AML;
D O I
10.1182/blood-2014-02-554667
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Some studies have suggested that cases of acute myeloid leukemia (AML) with low levels of FLT3 internal tandem duplications (FLT3(ITD)) do not have a worse prognosis if there is a concomitant NPM1(MUT)ation, although this is controversial. To clarify this therapeutically important issue, we have analyzed FLT3(ITD) and NPM1(MUT) levels in 1609 younger adult cases of cytogenetically intermediate-risk AML. The cumulative incidence of relapse was increased in NPM1(MUT) cases by the presence of a FLT3(ITD), but did not differ markedly according to FLT3(ITD) level. This remained true when allowance was made for poor leukemic cell purity by adjustment of the FLT3(ITD) level to the measured NPM1(MUT) level. If consolidation therapies are to be determined by relapse risk, then NPM1(MUT) cases with low-level FLT3(ITD) should not be considered as good risk without further studies. AML 12 and AML 15 are registered at http://www.controlled-trials.com under ISRCTN17833622 and ISRCTN17161961, respectively.
引用
收藏
页码:273 / 276
页数:4
相关论文
共 11 条
  • [1] The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach
    Cornelissen, Jan J.
    Gratwohl, Alois
    Schlenk, Richard F.
    Sierra, Jorge
    Bornhaeuser, Martin
    Juliusson, Gunnar
    Racil, Zdenek
    Rowe, Jacob M.
    Russell, Nigel
    Mohty, Mohamad
    Lowenberg, Bob
    Socie, Gerard
    Niederwieser, Dietger
    Ossenkoppele, Gert J.
    [J]. NATURE REVIEWS CLINICAL ONCOLOGY, 2012, 9 (10) : 579 - 590
  • [2] 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
    Gale, Rosemary E.
    Green, Claire
    Allen, Christopher
    Mead, Adam J.
    Burnett, Alan K.
    Hils, Robert K.
    Linch, David C.
    [J]. BLOOD, 2008, 111 (05) : 2776 - 2784
  • [3] 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
    Grimwade, David
    Hills, Robert K.
    Moorman, Anthony V.
    Walker, Helen
    Chatters, Stephen
    Goldstone, Anthony H.
    Wheatley, Keith
    Harrison, Christine J.
    Burnett, Alan K.
    [J]. BLOOD, 2010, 116 (03) : 354 - 365
  • [4] Molecular Genetics of Adult Acute Myeloid Leukemia: Prognostic and Therapeutic Implications
    Marcucci, Guido
    Haferlach, Torsten
    Doehner, Hartmut
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (05) : 475 - 486
  • [5] Acute Myeloid Leukemia Clinical Practice Guidelines in Oncology
    O'Donnell, Margaret R.
    Abboud, Camille N.
    Altman, Jessica
    Appelbaum, Frederick R.
    Arber, Daniel A.
    Attar, Eyal
    Borate, Uma
    Coutre, Steven E.
    Damon, Lloyd E.
    Goorha, Salil
    Lancet, Jeffrey
    Maness, Lori J.
    Marcucci, Guido
    Millenson, Michael M.
    Moore, Joseph O.
    Ravandi, Farhad
    Shami, Paul J.
    Smith, B. Douglas
    Stone, Richard M.
    Strickland, Stephen A.
    Tallman, Martin S.
    Wang, Eunice S.
    Naganuma, Maoko
    Gregory, Kristina M.
    [J]. JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2012, 10 (08): : 984 - 1021
  • [6] Genetic profiling in acute myeloid leukaemia - where are we and what is its role in patient management
    Ofran, Yishai
    Rowe, Jacob M.
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2013, 160 (03) : 303 - 320
  • [7] 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
    Pratcorona, Marta
    Brunet, Salut
    Nomdedeu, Josep
    Maria Ribera, Josep
    Tormo, Mar
    Duarte, Rafael
    Escoda, Lourdes
    Guardia, Ramon
    Queipo de Llano, M. Paz
    Salamero, Olga
    Bargay, Joan
    Pedro, Carmen
    Maria Marti, Josep
    Torrebadell, Montserrat
    Diaz-Beya, Marina
    Camos, Mireia
    Colomer, Dolors
    Hoyos, Montserrat
    Sierra, Jorge
    Esteve, Jordi
    [J]. BLOOD, 2013, 121 (14) : 2734 - 2738
  • [8] The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype
    Schneider, Friederike
    Hoster, Eva
    Unterhalt, Michael
    Schneider, Stephanie
    Dufour, Annika
    Benthaus, Tobias
    Mellert, Gudrun
    Zellmeier, Evelyn
    Kakadia, Purvi M.
    Bohlander, Stefan K.
    Feuring-Buske, Michaela
    Buske, Christian
    Braess, Jan
    Heinecke, Achim
    Sauerland, Maria C.
    Berdel, Wolfgang E.
    Buechner, Thomas
    Woermann, Bernhard J.
    Hiddemann, Wolfgang
    Spiekermann, Karsten
    [J]. BLOOD, 2012, 119 (19) : 4383 - 4386
  • [9] Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia
    Schnittger, S.
    Bacher, U.
    Kern, W.
    Alpermann, T.
    Haferlach, C.
    Haferlach, T.
    [J]. LEUKEMIA, 2011, 25 (08) : 1297 - 1304
  • [10] Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia:: association with FAB subtypes and identification of subgroups with poor prognosis
    Thiede, C
    Steudel, C
    Mohr, B
    Schaich, M
    Schäkel, U
    Platzbecker, U
    Wermke, M
    Bornhäuser, M
    Ritter, M
    Neubauer, A
    Ehninger, G
    Illmer, T
    [J]. BLOOD, 2002, 99 (12) : 4326 - 4335