TY - JOUR
T1 - Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation
AU - Schlenk, Richard F.
AU - Kayser, Sabine
AU - Bullinger, Lars
AU - Kobbe, Guido
AU - Casper, Jochen
AU - Ringhoffer, Mark
AU - Held, Gerhard
AU - Brossart, Peter
AU - Lübbert, Michael
AU - Salih, Helmut R.
AU - Kindler, Thomas
AU - Horst, Heinz A.
AU - Wulf, Gerald
AU - Nachbaur, David
AU - Götze, Katharina
AU - Lamparter, Alexander
AU - Paschka, Peter
AU - Gaidzik, Verena I.
AU - Teleanu, Veronica
AU - Späth, Daniela
AU - Benner, Axel
AU - Krauter, Jürgen
AU - Ganser, Arnold
AU - Döhner, Hartmut
AU - Döhner, Konstanze
N1 - Publisher Copyright:
© 2014 by The American Society of Hematology.
PY - 2014/9/30
Y1 - 2014/9/30
N2 - 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 5 .004) and IS in the tyrosine kinase domain 1 (TKD1, P 5 .06) were associated with low complete remission (CR) rates. After postremission therapy including intensive chemotherapy (n 5 121) or autologous hematopoietic stem cell transplantation (HSCT, n 5 17), an allelic ratio ≥ 0.51 was associated with an unfavorable relapse-free (RFS,P5.0008) and overall survival (OS, P5.004); after allogeneic HSCT (n593), outcome was significantly improved in patients with a high allelic ratio (RFS, P5.02; OS,P5.03), whereas no benefit was seen in patients with a low allelic ratio (RFS, P 5 .38; OS, P 5 .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.
AB - 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 5 .004) and IS in the tyrosine kinase domain 1 (TKD1, P 5 .06) were associated with low complete remission (CR) rates. After postremission therapy including intensive chemotherapy (n 5 121) or autologous hematopoietic stem cell transplantation (HSCT, n 5 17), an allelic ratio ≥ 0.51 was associated with an unfavorable relapse-free (RFS,P5.0008) and overall survival (OS, P5.004); after allogeneic HSCT (n593), outcome was significantly improved in patients with a high allelic ratio (RFS, P5.02; OS,P5.03), whereas no benefit was seen in patients with a low allelic ratio (RFS, P 5 .38; OS, P 5 .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.
UR - http://www.scopus.com/inward/record.url?scp=84914163645&partnerID=8YFLogxK
U2 - 10.1182/blood-2014-05-578070
DO - 10.1182/blood-2014-05-578070
M3 - Article
C2 - 25270908
AN - SCOPUS:84914163645
SN - 0006-4971
VL - 124
SP - 3441
EP - 3449
JO - Blood
JF - Blood
IS - 23
ER -