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Blood. 2014 Nov 27;124(23):3441-9. doi: 10.1182/blood-2014-05-578070. Epub 2014 Sep 30.

Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation.

Author information

1
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
2
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;
3
Department of Oncology and Hematology, Klinikum Oldenburg, Oldenburg, Germany;
4
Department of Internal Medicine III, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany;
5
Department of Internal Medicine I, University Hospital of Saarland, Homburg, Germany;
6
Department of Internal Medicine III, University Hospital of Bonn, Bonn, Germany;
7
Department of Hematology and Oncology, University Hospital of Freiburg, Freiburg, Germany;
8
Department of Hematology and Oncology, Eberhard-Karls University, Tübingen, Germany;
9
Department of Medicine III, Johannes Gutenberg-University Mainz, Mainz, Germany;
10
Department of Internal Medicine II, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany;
11
Department of Hematology and Oncology, University Hospital of Göttingen, Göttingen, Germany;
12
Department of Internal Medicine V, University Hospital Innsbruck, Innsbruck, Austria;
13
Department of Internal Medicine III, Technical University of Munich, Munich, Germany;
14
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany; and.
15
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Abstract

The objective was to evaluate the prognostic and predictive impact of allelic ratio and insertion site (IS) of internal tandem duplications (ITDs), as well as concurrent gene mutations, with regard to postremission therapy in 323 patients with FLT3-ITD-positive acute myeloid leukemia (AML). Increasing FLT3-ITD allelic ratio (P = .004) and IS in the tyrosine kinase domain 1 (TKD1, P = .06) were associated with low complete remission (CR) rates. After postremission therapy including intensive chemotherapy (n = 121) or autologous hematopoietic stem cell transplantation (HSCT, n = 17), an allelic ratio ≥ 0.51 was associated with an unfavorable relapse-free (RFS, P = .0008) and overall survival (OS, P = .004); after allogeneic HSCT (n = 93), outcome was significantly improved in patients with a high allelic ratio (RFS, P = .02; OS, P = .03), whereas no benefit was seen in patients with a low allelic ratio (RFS, P = .38; OS, P = .64). Multivariable analyses revealed a high allelic ratio as a predictive factor for the beneficial effect of allogeneic HSCT; ITD IS in TKD1 remained an unfavorable factor, whereas no prognostic impact of concurrent gene mutations was observed. The clinical trials described herein were previously published or are registered as follows: AMLHD93 and AMLHD98A, previously published; AML SG 07-04, ClinicalTrials.gov identifier #NCT00151242.

PMID:
25270908
DOI:
10.1182/blood-2014-05-578070
[Indexed for MEDLINE]
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