Prognostic significance of FLT3-ITD in pediatric acute myeloid leukemia: a meta-analysis of cohort studies
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The purpose of the study was to assess the effect of the internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) on the outcome in pediatric acute myeloid leukemia (AML) patients. We identified eligible studies from several databases including PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) (from January 1995 to July 2015). Ten studies of 1661 pediatric patients with AML were included in exploring the relationship between the FLT3-ITD and overall survival (OS)/event free survival (EFS). Pediatric patients with AML with FLT3-ITD had worse OS [HR = 2.19 (1.60–3.01)]/EFS [HR = 1.70 (1.37–2.11)] than those patients without FLT3-ITD. Furthermore, FLT3-ITD had unfavorable effect on OS/EFS in the subgroups of NOS, uni/multivariate model, number of patients, the length of following-up, and patient source. The findings of this meta-analysis indicated that FLT3-ITD had negative impact on pediatric patients with AML.
KeywordsAcute myeloid leukemia FLT3-ITD Pediatric Meta-analysis
This study is funded by project supported by Science and Technology Department of Hebei Province (No. 152777206).
Compliance with ethical standards
Conflicts of interest
All the authors declare that they have no conflict of interest.
- 1.Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–474CrossRefPubMedGoogle Scholar
- 4.Fröhling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K, Döhner H, Döhner K (2002) Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood 100:4372–4380CrossRefPubMedGoogle Scholar
- 5.Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, Löffler H, Sauerland CM, Serve H, Büchner T (2002) Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 100:59–66CrossRefPubMedGoogle Scholar
- 6.Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U, Wermke M, Bornhäuser M, Ritter M, Neubauer A (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99:4326–4335CrossRefPubMedGoogle Scholar
- 10.Balgobind BV, Hollink IH, Arentsen-Peters ST, Zimmermann M, Harbott J, Beverloo HB, von Bergh AR, Cloos J, Kaspers GJ, de Haas V (2011) Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia. Haematologica 96:1478–1487CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux P, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Internal Med 151:W-65–W-94CrossRefGoogle Scholar
- 16.Wells G, Shea B, O’connell D, Peterson J, Welch V, Losos M, Tugwell P (2000) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analysesGoogle Scholar
- 19.Deeks J, Higgins J, Altman D (2011) Chapter 9—analysing data and undertaking meta-analyses: Cochrane handbook for systematic reviews of interventions, Version 5.1.0 [updated March 2011]Google Scholar
- 22.Ruan M, Wang Y, Zhang L, Liu T, Liu F, Liu X, Zhang J, Zou Y, Chen Y, Zhu X (2011) FLT3 mutations in children with acute myeloid leukemia: a single center study. Zhongguo dang dai er ke za zhi (Chin J Contemp Pediatr) 13:863–866Google Scholar
- 28.Klusmann J-H, Reinhardt D, Zimmermann M, Kremens B, Vormoor J, Dworzak M, Creutzig U, Klingebiel T (2012) The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study. Haematologica 97:21–29CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Creutzig U, Zimmermann M, Bourquin J-P, Dworzak MN, Fleischhack G, Graf N, Klingebiel T, Kremens B, Lehrnbecher T, von Neuhoff C (2013) Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood 122:37–43CrossRefPubMedGoogle Scholar
- 30.von Neuhoff C, Reinhardt D, Sander A, Zimmermann M, Bradtke J, Betts DR, Zemanova Z, Stary J, Bourquin J-P, Haas OA (2010) Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol 2009(25):6321Google Scholar
- 31.Hollink I, Zwaan C, Zimmermann M, Arentsen-Peters T, Pieters R, Cloos J, Kaspers G, de Graaf S, Harbott J, Creutzig U (2009) Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia 23:262–270CrossRefPubMedGoogle Scholar
- 32.Mizushima Y, Taki T, Shimada A, Yui Y, Hiraumi Y, Matsubara H, Watanabe M, K-i Watanabe, Kamitsuji Y, Hayashi Y (2010) Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype: a study by the Japanese Childhood AML Cooperative Study Group. Int J Hematol 91:831–837CrossRefPubMedGoogle Scholar