LOCALIZATION OF FLT3-ITD IS ASSOCIATED WITH RESPONSE TO INDUCTION CHEMOTHERAPY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Schnetzke U. 06/09/16; 134542; PB1642
Dr. Ulf Schnetzke
Contributions
Contributions
Abstract
Abstract: PB1642
Type: Publication Only
Background
FLT3-ITDs (internal tandem duplications) represent the most frequent molecular aberrations in acute myeloid leukemia (AML) that are both virtually patient-specific and associated with a higher probability of relapse. Several studies addressed the question whether the diversity of FLT3-ITD affects the clinical outcome of AML patients. We present patient-specific sequence analysis of FLT3-ITD-positive AML patients and its correlation with clinical data.
Aims
FLT3-ITD sequence analysis focused on ITD localization and the presence of distinct amino acid motives. We sought to establish a relationship between the localization of the internal tandem duplication in FLT3 and response to therapy.
Methods
43 patients (26 female, median age 57 years, 84% with de novo AML) diagnosed and treated in a single center were retrospectively analysed.All patients received intensive induction chemotherapy according to one of the following protocols of the Ostdeutsche Studiengruppe für Hämatologie und Onkologie (OSHO): AML96 or AML2002 protocol containing idarubicine for patients up to 60 years old and AML97 or AML2004 protocol containing mitoxantrone for elderly patients.
Results
FLT3-ITD localization more downstream can be correlated with impaired leukemia-free survival (LFS) while the level of significance is not reached in our small cohort of AML patients. In contrast, all investigated amino acid motifs (e.g. YVDFREY) had no impact on the clinical outcome. Importantly, the probability to achieve a complete remission (CR) after AML induction chemotherapy is affected by the localization of the internal tandem duplication. In detail, CR rate is significantly higher in those patients who present with FLT3-ITD localized towards the N-terminus (86.4% vs 57.1%, p=0.045, Chi squared test).
Conclusion
We hypothesize that FLT3-ITDs that are located closer to the C-terminus of FLT3 are associated with an unfavorable prognosis due to a lower CR rate following induction chemotherapy of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Chemotherapy, Flt3-ITD
Type: Publication Only
Background
FLT3-ITDs (internal tandem duplications) represent the most frequent molecular aberrations in acute myeloid leukemia (AML) that are both virtually patient-specific and associated with a higher probability of relapse. Several studies addressed the question whether the diversity of FLT3-ITD affects the clinical outcome of AML patients. We present patient-specific sequence analysis of FLT3-ITD-positive AML patients and its correlation with clinical data.
Aims
FLT3-ITD sequence analysis focused on ITD localization and the presence of distinct amino acid motives. We sought to establish a relationship between the localization of the internal tandem duplication in FLT3 and response to therapy.
Methods
43 patients (26 female, median age 57 years, 84% with de novo AML) diagnosed and treated in a single center were retrospectively analysed.All patients received intensive induction chemotherapy according to one of the following protocols of the Ostdeutsche Studiengruppe für Hämatologie und Onkologie (OSHO): AML96 or AML2002 protocol containing idarubicine for patients up to 60 years old and AML97 or AML2004 protocol containing mitoxantrone for elderly patients.
Results
FLT3-ITD localization more downstream can be correlated with impaired leukemia-free survival (LFS) while the level of significance is not reached in our small cohort of AML patients. In contrast, all investigated amino acid motifs (e.g. YVDFREY) had no impact on the clinical outcome. Importantly, the probability to achieve a complete remission (CR) after AML induction chemotherapy is affected by the localization of the internal tandem duplication. In detail, CR rate is significantly higher in those patients who present with FLT3-ITD localized towards the N-terminus (86.4% vs 57.1%, p=0.045, Chi squared test).
Conclusion
We hypothesize that FLT3-ITDs that are located closer to the C-terminus of FLT3 are associated with an unfavorable prognosis due to a lower CR rate following induction chemotherapy of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Chemotherapy, Flt3-ITD
Abstract: PB1642
Type: Publication Only
Background
FLT3-ITDs (internal tandem duplications) represent the most frequent molecular aberrations in acute myeloid leukemia (AML) that are both virtually patient-specific and associated with a higher probability of relapse. Several studies addressed the question whether the diversity of FLT3-ITD affects the clinical outcome of AML patients. We present patient-specific sequence analysis of FLT3-ITD-positive AML patients and its correlation with clinical data.
Aims
FLT3-ITD sequence analysis focused on ITD localization and the presence of distinct amino acid motives. We sought to establish a relationship between the localization of the internal tandem duplication in FLT3 and response to therapy.
Methods
43 patients (26 female, median age 57 years, 84% with de novo AML) diagnosed and treated in a single center were retrospectively analysed.All patients received intensive induction chemotherapy according to one of the following protocols of the Ostdeutsche Studiengruppe für Hämatologie und Onkologie (OSHO): AML96 or AML2002 protocol containing idarubicine for patients up to 60 years old and AML97 or AML2004 protocol containing mitoxantrone for elderly patients.
Results
FLT3-ITD localization more downstream can be correlated with impaired leukemia-free survival (LFS) while the level of significance is not reached in our small cohort of AML patients. In contrast, all investigated amino acid motifs (e.g. YVDFREY) had no impact on the clinical outcome. Importantly, the probability to achieve a complete remission (CR) after AML induction chemotherapy is affected by the localization of the internal tandem duplication. In detail, CR rate is significantly higher in those patients who present with FLT3-ITD localized towards the N-terminus (86.4% vs 57.1%, p=0.045, Chi squared test).
Conclusion
We hypothesize that FLT3-ITDs that are located closer to the C-terminus of FLT3 are associated with an unfavorable prognosis due to a lower CR rate following induction chemotherapy of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Chemotherapy, Flt3-ITD
Type: Publication Only
Background
FLT3-ITDs (internal tandem duplications) represent the most frequent molecular aberrations in acute myeloid leukemia (AML) that are both virtually patient-specific and associated with a higher probability of relapse. Several studies addressed the question whether the diversity of FLT3-ITD affects the clinical outcome of AML patients. We present patient-specific sequence analysis of FLT3-ITD-positive AML patients and its correlation with clinical data.
Aims
FLT3-ITD sequence analysis focused on ITD localization and the presence of distinct amino acid motives. We sought to establish a relationship between the localization of the internal tandem duplication in FLT3 and response to therapy.
Methods
43 patients (26 female, median age 57 years, 84% with de novo AML) diagnosed and treated in a single center were retrospectively analysed.All patients received intensive induction chemotherapy according to one of the following protocols of the Ostdeutsche Studiengruppe für Hämatologie und Onkologie (OSHO): AML96 or AML2002 protocol containing idarubicine for patients up to 60 years old and AML97 or AML2004 protocol containing mitoxantrone for elderly patients.
Results
FLT3-ITD localization more downstream can be correlated with impaired leukemia-free survival (LFS) while the level of significance is not reached in our small cohort of AML patients. In contrast, all investigated amino acid motifs (e.g. YVDFREY) had no impact on the clinical outcome. Importantly, the probability to achieve a complete remission (CR) after AML induction chemotherapy is affected by the localization of the internal tandem duplication. In detail, CR rate is significantly higher in those patients who present with FLT3-ITD localized towards the N-terminus (86.4% vs 57.1%, p=0.045, Chi squared test).
Conclusion
We hypothesize that FLT3-ITDs that are located closer to the C-terminus of FLT3 are associated with an unfavorable prognosis due to a lower CR rate following induction chemotherapy of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Chemotherapy, Flt3-ITD
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