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

Item Type:	Article
Title:	Differential impact of allelic ratio and insertion site in FLT3-ITD–positive AML with respect to allogeneic transplantation
Creators Name:	Schlenk, R.F. and Kayser, S. and Bullinger, L. and Kobbe, G. and Casper, J. and Ringhoffer, M. and Held, G. and Brossart, P. and Lübbert, M. and Salih, H.R. and Kindler, T. and Horst, H.A. and Wulf, G. and Nachbaur, D. and Götze, K. and Lamparter, A. and Paschka, P. and Gaidzik, V.I. and Teleanu, V. and Späth, D. and Benner, A. and Krauter, J. and Ganser, A. and Döhner, H. and Döhner, K.
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.
Keywords:	Acute Myeloid Leukemia, Alleles, DNA Mutational Analysis, Gene Duplication, Gene Frequency, Hematopoietic Stem Cell Transplantation, Homologous Transplantation, Insertional Mutagenesis, Tandem Repeat Sequences, Tertiary Protein Structure, Treatment Outcome, fms-Like Tyrosine Kinase 3
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	124
Number:	23
Page Range:	3441-3449
Date:	27 November 2014
Official Publication:	https://doi.org/10.1182/blood-2014-05-578070
PubMed:	View item in PubMed

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