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CLINICAL AND PROGNOSTIC VALUE OF FLT3 MUTATIONS IN ACUTE MYELOID LEUKEMIA PATIENTS IN ROUTINE CLINICAL PRACTICE - SINGLE CENTER EXPERIENCE
Author(s): ,
Asiyat Radzhabova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Sergey Voloshin
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Irina Martynkevich
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Vasily Shuvaev
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Marina Ivanova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Ekaterina Motyko
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Natalya Cybakova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Liubov Polushkina
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Dzharyat Shikhbabaeva
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Nadezhda Potikhonova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Sofya Tyranova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Marina Zenina
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
,
Svetlana Kudryashova
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
Alexander Chechetkin
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
(Abstract release date: 05/18/17) EHA Library. Radzhabova A. 05/18/17; 182396; PB1682
Asiyat Radzhabova
Asiyat Radzhabova
Contributions
Abstract

Abstract: PB1682

Type: Publication Only

Background
Detection of FLT3 gene mutations in acute myeloid leukemia (AML) now recognized as an unfavorable factor that affects the disease course, emerging the risk of relapses and overall survival (OS) shortening. Although about 30% of AML patients harbor one of the FLT3 gene lesion, at present there are no internationally standardized assays to quantify FLT3 mutation burden and no results of randomized clinical trials intended to individualize AML treatment based on FLT3 status. Some hematologists advocate to allo-SCT as consolidation in FLT3 ITD+ patients, but this way could be hard in frail and old patients and in countries with low access to transplant techniques. On the other hand, the development of target drug therapy – FLT3-kinase inhibitors gives us a new hope for improvement in the treatment results of such poor-prognosis subset of AML patients.

Aims
To assess the frequency of FLT3 gene mutations and its impact on clinical parameters and overall survival of the patients with acute myeloid leukemia (AML) in routine clinical practice.

Methods
We have analyzed FLT3 gene mutation frequencies, complete blood count (CBC) parameters, karyotype and survival outcomes per FLT3-mutation status in 199 patients with AML (83 male / 116 female). The median age at diagnosis was 52 years (20-86 years). To determine FLT3 gene mutations we used the method of polymerase chain reaction (PCR) with subsequent restriction. FLT3 gene mutations were classified as internal tandem duplication (FLT3-ITD) and point mutation in the 'A-loop' (FLT3-TKD). Statistical analysis was included Kruskall-Wallis ANOVA and Kaplan-Meyer curves.

Results

We observed next FLT3 gene mutations rates: FLT3-ITD - 22.6% (45/199), FLT3-TKD 5.5% (11/199), FLT3-ITD and FLT3-TKD in combination 1.0% (2/199), other 70.8% (141/199) patients had no mutations (FLT3-). CBC data at the time of diagnosis were as follows (median (max-min)):
· FLT3-ITD: Hb 9.7 (3.7-13.0) g/dl, WBC 40.3 (0.6-400.0) x 109/l, blasts 80% (21-100), platelets 60 (2-140) x 109/L;
· FLT3-TKD: Hb 10.2 (5.8-12.8) g/dl, WBC 62.4 (1.7-362.0) x 109/l, blasts 68% (23-100), platelets 55 (12-115) x 109/L;
· FLT3-ITD+TKD: Hb 5.8, 8.4 g/dl, WBC 37.0, 157.0 x 109/l, blasts 65%, 86%, platelets 38, 186 x 109/L;
· FLT3-: Hb 9.0 (2.8-14.0) g/dl, WBC 12.9 (1.0-260.0) x 109/l, blasts 64% (20-103), platelets 63 (1-334) x 109/L;
Significant differences across the groups were seen only in WBC and blasts. Chromosomal aberrations were revealed in 38% of FLT3-ITD, 64% of FLT3-TKD, none of FLT3-ITD+TKD and 51% of FLT3- patients. All patients received chemotherapy (7+3, 5+2, HAM). Transplantation of hematopoietic stem cells (SCT) was performed in 28 (allo/auto 17/11) (14%) patients: FLT3-ITD allo-3; FLT3-TKD allo-1, auto-1; FLT3- allo-13, auto-10. We found significant (p=0.00024) differences regarding to OS between FLT3-ITD, FLT3-TKD and FLT3- patients (Fig.1). Median survival times were: 5.1 months for FLT3-ITD, 7.1 months for FLT3-TKD and 13.0 months for FLT3- patients.

Conclusion
We confirmed the role of FLT3 gene mutations as an unfavorable factor for AML patients in routine clinical practice by own experience. The investigation of qualitative assessment potential and target therapy value especially in SCT ineligible FLT3 gene mutations positive patients has of great value for AML management.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Practice, Flt3-ITD, FLT3, AML

Abstract: PB1682

Type: Publication Only

Background
Detection of FLT3 gene mutations in acute myeloid leukemia (AML) now recognized as an unfavorable factor that affects the disease course, emerging the risk of relapses and overall survival (OS) shortening. Although about 30% of AML patients harbor one of the FLT3 gene lesion, at present there are no internationally standardized assays to quantify FLT3 mutation burden and no results of randomized clinical trials intended to individualize AML treatment based on FLT3 status. Some hematologists advocate to allo-SCT as consolidation in FLT3 ITD+ patients, but this way could be hard in frail and old patients and in countries with low access to transplant techniques. On the other hand, the development of target drug therapy – FLT3-kinase inhibitors gives us a new hope for improvement in the treatment results of such poor-prognosis subset of AML patients.

Aims
To assess the frequency of FLT3 gene mutations and its impact on clinical parameters and overall survival of the patients with acute myeloid leukemia (AML) in routine clinical practice.

Methods
We have analyzed FLT3 gene mutation frequencies, complete blood count (CBC) parameters, karyotype and survival outcomes per FLT3-mutation status in 199 patients with AML (83 male / 116 female). The median age at diagnosis was 52 years (20-86 years). To determine FLT3 gene mutations we used the method of polymerase chain reaction (PCR) with subsequent restriction. FLT3 gene mutations were classified as internal tandem duplication (FLT3-ITD) and point mutation in the 'A-loop' (FLT3-TKD). Statistical analysis was included Kruskall-Wallis ANOVA and Kaplan-Meyer curves.

Results

We observed next FLT3 gene mutations rates: FLT3-ITD - 22.6% (45/199), FLT3-TKD 5.5% (11/199), FLT3-ITD and FLT3-TKD in combination 1.0% (2/199), other 70.8% (141/199) patients had no mutations (FLT3-). CBC data at the time of diagnosis were as follows (median (max-min)):
· FLT3-ITD: Hb 9.7 (3.7-13.0) g/dl, WBC 40.3 (0.6-400.0) x 109/l, blasts 80% (21-100), platelets 60 (2-140) x 109/L;
· FLT3-TKD: Hb 10.2 (5.8-12.8) g/dl, WBC 62.4 (1.7-362.0) x 109/l, blasts 68% (23-100), platelets 55 (12-115) x 109/L;
· FLT3-ITD+TKD: Hb 5.8, 8.4 g/dl, WBC 37.0, 157.0 x 109/l, blasts 65%, 86%, platelets 38, 186 x 109/L;
· FLT3-: Hb 9.0 (2.8-14.0) g/dl, WBC 12.9 (1.0-260.0) x 109/l, blasts 64% (20-103), platelets 63 (1-334) x 109/L;
Significant differences across the groups were seen only in WBC and blasts. Chromosomal aberrations were revealed in 38% of FLT3-ITD, 64% of FLT3-TKD, none of FLT3-ITD+TKD and 51% of FLT3- patients. All patients received chemotherapy (7+3, 5+2, HAM). Transplantation of hematopoietic stem cells (SCT) was performed in 28 (allo/auto 17/11) (14%) patients: FLT3-ITD allo-3; FLT3-TKD allo-1, auto-1; FLT3- allo-13, auto-10. We found significant (p=0.00024) differences regarding to OS between FLT3-ITD, FLT3-TKD and FLT3- patients (Fig.1). Median survival times were: 5.1 months for FLT3-ITD, 7.1 months for FLT3-TKD and 13.0 months for FLT3- patients.

Conclusion
We confirmed the role of FLT3 gene mutations as an unfavorable factor for AML patients in routine clinical practice by own experience. The investigation of qualitative assessment potential and target therapy value especially in SCT ineligible FLT3 gene mutations positive patients has of great value for AML management.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Practice, Flt3-ITD, FLT3, AML

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