logo

Is FLT3 Internal Tandem Duplication an Unfavorable Risk Factor for High Risk Children with Acute Myeloid Leukemia? - Polish Experience

Authors

  • K. Pawinska-Wasikowska

    Department ofPediatric Oncology and Hematology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland

  • T. Ksiazek

    Department ofPediatric Oncology and Hematology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland

  • A. Wieczorek

    Department ofPediatric Oncology and Hematology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland

  • M. Matysiak

    Department of Pediatrics, Hematology and Oncology, Medical University, Warsaw, Poland

  • B. Fic-Sikorska

    Department of Pediatrics, Hematology and Oncology, Medical University, Warsaw, Poland

  • E. Adamkiewicz-Drozynska

    Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdansk, Poland

  • L. Maciejka-Kapuscinska

    Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdansk, Poland

  • A. Chybicka

    Department of Pediatric Transplantology, Oncology and Hematology, Medical Academy of Wroclaw, Poland

  • K. Potocka

    Department of Pediatric Transplantology, Oncology and Hematology, Medical Academy of Wroclaw, Poland

  • J. Wachowiak

    Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland

  • J. Skalska-Sadowska

    Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland

  • J. Kowalczyk

    Department of Hematology and Oncology, Medical University, Lublin, Poland

  • B. Wojcik

    Department of Hematology and Oncology, Medical University, Lublin, Poland

  • M. Wysocki

    Department of Pediatrics, Hematology and Oncology, Institute of Pediatrics, Medical Academy, Bydgoszcz, Poland

  • S. Koltan

    Department of Pediatrics, Hematology and Oncology, Institute of Pediatrics, Medical Academy, Bydgoszcz, Poland

  • M. Krawczuk-Rybak

    Department of Pediatric Hematology and Oncology, Medical University, Bialystok, Poland

  • K. Muszynska-Roslan

    Department of Pediatric Hematology and Oncology, Medical University, Bialystok, Poland

  • W. Mlynarski

    Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University, Lodz, Poland

  • M. Stolarska

    Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University, Lodz, Poland

  • T. Urasinski

    First Department of Pediatrics, Pomeranian Medical Academy, Szczecin, Poland

  • E. Kamienska

    First Department of Pediatrics, Pomeranian Medical Academy, Szczecin, Poland

  • T. Szczepanski

    Department of Pediatric Hematology and Oncology, Silesian Medical University, Zabrze, Poland

  • R. Tomaszewska

    Department of Pediatric Hematology and Oncology, Silesian Medical University, Zabrze, Poland

  • G. Sobol-Milejska

    Oncology and Hematology Unit of Pediatric Department, Silesian Medical University, Katowice, Poland

  • A. Mizia-Malarz

    Oncology and Hematology Unit of Pediatric Department, Silesian Medical University, Katowice, Poland

  • G. Karolczyk

    Oncology and Hematology Unit of Pediatric Hospital, Kielce, Poland

  • J. Pohorecka

    Oncology and Hematology Unit of Pediatric Hospital, Kielce, Poland

  • M. Wieczorek

    Pediatrics and Oncology Center, Chorzow, Poland

  • I. Karpinska-Derda

    Pediatrics and Oncology Center, Chorzow, Poland

  • W. Balwierz

    Department ofPediatric Oncology and Hematology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland

DOI:

https://doi.org/10.6000/1929-2279.2013.02.04.3

Keywords:

FLT3/ITD mutation, acute myeloid leukemia, children, treatment result, high risk group.

Abstract

According to the AML-BFM 2004 Interim, a treatment protocol used in Poland since 2005, presence of FLT3 internal tandem duplication (FLT3/ITD) qualifies a patient with acute myeloid leukemia (AML) to a high-risk group (HRG). The present study was aimed to identify the prevalence of FLT3/ITD in children with AML in Poland and to evaluate its prognostic significance in the HRG patients. Out of 291 children with de novo AML treated in 14 Polish centers between January 2006 and December 2012, samples from 174 patients were available for FLT3/ITD analysis. Among study patients 108 children (61.7%) were qualified to HRG. Genomic DNA samples from bone marrow were tested for identification of FLT3/ITD mutation by PCR amplification of exon 14 and 15 of FLT3 gene. Clinical features and treatment outcome in patients with and without FLT3/ITD were analyzed in the study. The FLT3/ITD was found in 14 (12.9%) of 108 HRG children. There were no significant differences between children with and without FLT3/ITD in age and FAB distribution. The white blood cells count in peripheral blood at diagnosis was significantly higher (p <0.01) in the children with FLT3/ITD. Over 5-year overall survival rate for FLT3/ITD positive children was worse (42.4%) comparing to FLT3/ITD negative children (58.9%), but the statistical difference was not significant. However, over 5-year survivals free from treatment failures were similar. The FLT3/ITD rate (12.9%) observed in the study corresponded to the published data. There was no significant impact of FLT3/ITD mutation on survival rates, although further studies are needed on this subject.

References

Varidman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937-51. http://dx.doi.org/10.1182/blood-2009-03-209262

Kaspers GJL. Pediatric acute myeloid leukemia. Expert Rev Anticancer Ther 2012; 12: 405-13. http://dx.doi.org/10.1586/era.12.1

Creutzig U, van den Heuvel-Eibrink MM, Gibson B, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood 2012; 120: 3187-205. http://dx.doi.org/10.1182/blood-2012-03-362608

Rubnitz JE, Inaba H. Childhood acute myeloid leukemia. Br J Haematol 2012; 159: 259-87. http://dx.doi.org/10.1111/bjh.12040

Balwierz W, Pawinska-Wasikowska K, Klekawka T, et al. Development of treatment and clinical results in childhood acute myeloid leukemia in Poland. Memo 2013; 6:54-62. http://dx.doi.org/10.1007/s12254-012-0061-9

Hatzimichael E, Georgiou G, Benetatos L, et al. Gene mutations and molecularly targeted therapies in acute myeloid leukemia. Am J Blood Res 2013; 3: 29-51.

Meshinchi S, Woods WG, Stirewalt DL, et al. Prevalence and prognosis significance of FLT3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 2001; 97: 89-94. http://dx.doi.org/10.1182/blood.V97.1.89

Meshinchi S, Alonzo TA, Stirewalt DL, et al. Clinical implications of FLT3 mutations in pediatric AML. Blood 2006; 108: 3654-61. http://dx.doi.org/10.1182/blood-2006-03-009233

Assem MM, Noshy MM, Elsayed GM, et al. FLT3 internal tandem duplication and JAK2 V617F mutations in de novo acute myelogenous leukemia: relation with induction of chemotherapy and overall survival. Life Sci J 2012; 9: 1053-60.

Dohner H, Gaidzik VI. Impact of genetic features on treatment decisions in AML. Hematology Am Soc Hematol Educ Program 2011; 1: 36-42. http://dx.doi.org/10.1182/asheducation-2011.1.36

Konodo M, Horibe K, Takahashi Y, et al. Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia. Med Pediatr Oncol 1999; 33: 525-29. http://dx.doi.org/10.1002/(SICI)1096-911X(199912)33:6<525::AID-MPO1>3.0.CO;2-8

Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12. Blood 2001; 98: 1752-59. http://dx.doi.org/10.1182/blood.V98.6.1752

Zwaan CM, Meshinchi S, Radich JP, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood 2003; 102: 2387-94. http://dx.doi.org/10.1182/blood-2002-12-3627

Yanada M, Matuso K, Suzuki T, Kiyoi H, Naoe T. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia 2005; 19: 1345-49. http://dx.doi.org/10.1038/sj.leu.2403838

Shimada A, Taki T, Koga D, et al. High WT1 mRNA expression after induction chemotherapy and FLT3-ITD have prognostic impact in pediatric acute myeloid leukemia: a study of the Japanese Childhood AML Cooperative Study Group. Int J Hematol 2012; 96: 469-76. http://dx.doi.org/10.1007/s12185-012-1163-1

Balgobind BV, Hollink HIM, Arentsen-Peters STCJM, et al. Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia. Haematologica 2011; 96: 1478-87. http://dx.doi.org/10.3324/haematol.2010.038976

Schneider F, Hoster E, Schneider S, et al. Age-dependent frequencies of NMP1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML). Ann Hematol 2012; 91: 9-18. http://dx.doi.org/10.1007/s00277-011-1280-6

Thol F, Kolking B, Damm F, et al. Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations. Genes Chromosomes Cancer 2012; 51: 689-95. http://dx.doi.org/10.1002/gcc.21955

Pigazzi M, Manara E, Bisio V, et al. Screening of novel genetic aberrations in pediatric acute myeloid leukemia: a report from the AIEOP AML-2002 study group. Blood 2012; 120: 3860-62. http://dx.doi.org/10.1182/blood-2012-09-454454

de Jonge HJM, Valk PJM, de Bont ESJM, et al. Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD. Haematologica 2011; 96: 1310-17. http://dx.doi.org/10.3324/haematol.2011.040592

Kutny MA, Moser BK, Laumann K, et al. FLT3 mutation status is a predictor of early death in pediatric acute promyelocytic leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer 2012; 59: 662-667. http://dx.doi.org/10.1002/pbc.24122

Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99: 4326-35. http://dx.doi.org/10.1182/blood.V99.12.4326

Lacayo NJ, Meshinchi S, Kinnunen P, et al. Gene expression profiles at diagnosis in de novo children AML patients identify FLT3 mutations with good clinical outcomes. Blood 2004; 104: 2646-54. http://dx.doi.org/10.1182/blood-2003-12-4449

Stirewalt DL, Kopecky KJ, Meshinchi S, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood 2006; 107: 3724-26. http://dx.doi.org/10.1182/blood-2005-08-3453

Buccisano F, Maurillo L, del Principe MI, et al. Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood 2012; 119: 332-41. http://dx.doi.org/10.1182/blood-2011-08-363291

Watt TC, Cooper T. Sorafenib as treatment of relapsed or refractory pediatric acute myelogenous leukemia. Pediatr Blood Cancer 2012; 59: 756-57. http://dx.doi.org/10.1002/pbc.23394

Man CH, Fung TK, Ho C, et al. Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favourable initial outcome and mechanisms of subsequent nonresposiveness associated with the emergence of a D835 mutation. Blood 2012; 119: 5133-43. http://dx.doi.org/10.1182/blood-2011-06-363960

Levis M, Ravandi F, Wang ES, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011; 117: 3294-301. http://dx.doi.org/10.1182/blood-2010-08-301796

Stone RM, Fisher T, Paquette R, et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia 2012; 26: 2061-68. http://dx.doi.org/10.1038/leu.2012.115

Downloads

Published

2013-11-28

Issue

Vol. 2 No. 4 (2013)

Section

Articles

How to Cite

Is FLT3 Internal Tandem Duplication an Unfavorable Risk Factor for High Risk Children with Acute Myeloid Leukemia? - Polish Experience. (2013). Journal of Cancer Research Updates, 2(4),  246-253. https://doi.org/10.6000/1929-2279.2013.02.04.3

Similar Articles

1-10 of 171

You may also start an advanced similarity search for this article.