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FLT3, NPM1, СЕВРА AND ТР53 MUTATIONS AT ACUTE PROMYELOCYTIC LEUKEMIA: PROGNOSTIC FACTORS AND CORRELATION WITH OTHER MARKERS WITHIN THE PATIENTS OF GOMEL REGION IN BELARUS
Author(s):
Zhanna Kozich
,
Zhanna Kozich
Affiliations:
Hematology,The Republican Research Center for Radiation Medicine and Human Ecology,Gomel,Belarus
Victor Martinkov
,
Victor Martinkov
Affiliations:
Molecular Genetics,The Republican Research Center for Radiation Medicine and Human Ecology,Gomel,Belarus
Arkadiy Silin
,
Arkadiy Silin
Affiliations:
Molecular Genetics,The Republican Research Center for Radiation Medicine and Human Ecology,Gomel,Belarus
Irina Tropashko
Irina Tropashko
Affiliations:
Molecular Genetics,The Republican Research Center for Radiation Medicine and Human Ecology,Gomel,Belarus
(Abstract release date: 05/18/17) EHA Library. Kozich Z. 05/18/17; 182414; PB1700
Dr. Zhanna Kozich
Dr. Zhanna Kozich
Contributions
PDF Abstract
Abstract

Abstract: PB1700

Type: Publication Only

Background
Acute Promyelocytic Leukemia (APL) is one of the favourable variant of acute myelocytic leukemias due to the usage of ATRA in the treatment simaltenously with chemotherapy. But relapses occur in 13-33% cases after achievement the remission and there are cases of early death from the bleeding. High leukocytosis, the presence of lymphoid immunophenotypic markers and gene mutations are important prognostic factors.

Aims
To examine prognostic factors in APL

Methods
The materials for research were the samples of whole venous blood and bone marrow of 40 patients with APL treated in the period of 2009-20016 in Hematology department for adults, Gomel. The diagnosis was proved by the presence t(15;17) or PML/RARA. Induction therapy was carried out according to the protocol «7+3» using ATRA. Immunophenotypic analysis was carried out by standard immunofluorescence methods. The method of polymerase chain reaction (PCR) with specific primer and following electrophoretic detection was used for recognition of gene mutations.

Results

Out of 40 examined patients (mean age 48,5),80%(32) achieved remission and 15.6%(5) subsequently relapsed after the first course of chemotherapy. Clinical, laboratory, molecular genetic and immunophenotypic data which could affect remission results and general survival rate were analyzed within all the patients. As a result, mutations were detected in 55% of cases. FLT3-ITD mutations were detected in 32,5%(13), NPM1 mutations in 12,5%(5), combination of FLT3-ITD and NPM1 in 7,5%(3), TP53 and CEBPA mutations were detected in 5%(2) and 12,5%(5) of cases respectively. After achievement of remission after the first course of chemotherapy NPM1 mutation remained at 6.2%(2). Mutations were identified more frequently within the patients with the absence of response to the therapy or with the developed relapse in a while. The worst prognosis had the patients with the combination of FLT3-ITD and NPM1 mutations. There were the patients with high leukocytosis, presence of CD56 and CD2 immunophenotypic markers, who didn’t achieve remission or had the recurrence when the treatment was dropped. The presence of leukocytosis was detected in 25% of cases, in 90% (9/10) of cases leukocytosis was combined with FLT3-ITD mutations and 80% of these patients subsequently had the recurrence. Within the patients with the combination of FLT3-ITD and NPM1 mutations who brought into remission after the first course of chemotherapy these mutations were not detected later on. There were the patients who had leukocytosis rate less than 20x10 9 * l and didn’t have CD56 and CD2(11,5%) at the time of verification. The presence of TP53 mutation was combined with high leukocytosis of the patient and with the absence of effect on the conducted therapy.
When analyzing the immunophenotypic markers CD56 and CD2, they were detected in 75% of the patients, but in the absence of gene mutations and leukocytosis, such patients had a favorable prognosis (16,7%(3/18, p = 0,046)).

Conclusion
Our results prove that the presence of only one of the signs is not a factor of high risk. Only combination of clinical, laboratory, molecular-genetic and immunophenotypic markers can include the patients into a high risk group and influence general survival rate.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Mutation, Leukemia

Abstract: PB1700

Type: Publication Only

Background
Acute Promyelocytic Leukemia (APL) is one of the favourable variant of acute myelocytic leukemias due to the usage of ATRA in the treatment simaltenously with chemotherapy. But relapses occur in 13-33% cases after achievement the remission and there are cases of early death from the bleeding. High leukocytosis, the presence of lymphoid immunophenotypic markers and gene mutations are important prognostic factors.

Aims
To examine prognostic factors in APL

Methods
The materials for research were the samples of whole venous blood and bone marrow of 40 patients with APL treated in the period of 2009-20016 in Hematology department for adults, Gomel. The diagnosis was proved by the presence t(15;17) or PML/RARA. Induction therapy was carried out according to the protocol «7+3» using ATRA. Immunophenotypic analysis was carried out by standard immunofluorescence methods. The method of polymerase chain reaction (PCR) with specific primer and following electrophoretic detection was used for recognition of gene mutations.

Results

Out of 40 examined patients (mean age 48,5),80%(32) achieved remission and 15.6%(5) subsequently relapsed after the first course of chemotherapy. Clinical, laboratory, molecular genetic and immunophenotypic data which could affect remission results and general survival rate were analyzed within all the patients. As a result, mutations were detected in 55% of cases. FLT3-ITD mutations were detected in 32,5%(13), NPM1 mutations in 12,5%(5), combination of FLT3-ITD and NPM1 in 7,5%(3), TP53 and CEBPA mutations were detected in 5%(2) and 12,5%(5) of cases respectively. After achievement of remission after the first course of chemotherapy NPM1 mutation remained at 6.2%(2). Mutations were identified more frequently within the patients with the absence of response to the therapy or with the developed relapse in a while. The worst prognosis had the patients with the combination of FLT3-ITD and NPM1 mutations. There were the patients with high leukocytosis, presence of CD56 and CD2 immunophenotypic markers, who didn’t achieve remission or had the recurrence when the treatment was dropped. The presence of leukocytosis was detected in 25% of cases, in 90% (9/10) of cases leukocytosis was combined with FLT3-ITD mutations and 80% of these patients subsequently had the recurrence. Within the patients with the combination of FLT3-ITD and NPM1 mutations who brought into remission after the first course of chemotherapy these mutations were not detected later on. There were the patients who had leukocytosis rate less than 20x10 9 * l and didn’t have CD56 and CD2(11,5%) at the time of verification. The presence of TP53 mutation was combined with high leukocytosis of the patient and with the absence of effect on the conducted therapy.
When analyzing the immunophenotypic markers CD56 and CD2, they were detected in 75% of the patients, but in the absence of gene mutations and leukocytosis, such patients had a favorable prognosis (16,7%(3/18, p = 0,046)).

Conclusion
Our results prove that the presence of only one of the signs is not a factor of high risk. Only combination of clinical, laboratory, molecular-genetic and immunophenotypic markers can include the patients into a high risk group and influence general survival rate.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Mutation, Leukemia

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