BCR-ABL1 TRANSCRIPTS E13A2 AND E14A2 IN RELATION TO SURVIVAL AND MOLECULAR RESPONSES IN CML PATIENTS IN BOSNIA
Author(s): ,
Amina Kurtovic-Kozaric
Affiliations:
Clinical Pathology, Cytology and Human Genetics,Clinical Center of the University of Sarajevo,Sarajevo,Bosnia and Herzegovina
,
Erna Islamagic
Affiliations:
Faculty of Science, University of Sarajevo,Sarajevo,Bosnia and Herzegovina
,
Semir Mesanovic
Affiliations:
Pathology,University Clinical Center Tuzla,Tuzla,Bosnia and Herzegovina
,
Adnan Burekovic
Affiliations:
Internal Medicine,Cantonal Hospital Zenica,Zenica,Bosnia and Herzegovina
,
Amna Uzunovic
Affiliations:
Internal Medicine,Cantonal Hospital Zenica,Zenica,Bosnia and Herzegovina
Sabira Kurtovic
Affiliations:
Hematology Clinic,Clinical Center of the University of Sarajevo,Sarajevo,Bosnia and Herzegovina
(Abstract release date: 05/14/20) EHA Library. Kurtovic-Kozaric A. 06/12/20; 297879; PB1963
Assoc. Prof. Amina Kurtovic-Kozaric
Assoc. Prof. Amina Kurtovic-Kozaric
Contributions
Abstract

Abstract: PB1963

Type: Publication Only

Background

Chronic myeloid leukaemia (CML) is a clonal disease of the haematopoietic stem cells that is driven by the chimeric BCR-ABL1 protein with aberrant tyrosine kinase activity. Chimeric BCR-ABL1 p210 protein results from several types of transcripts, where e13a2 and e14a2 account for the vast majority of cases.

Aims

We analysed the correlation between BCR-ABL1 transcript type and overall survival, the probability of achieving CCyR (complete cytogenetic response), MMR (major molecular response), and deep molecular response (MR4 and MR5). 

Methods

Out of 245 newly diagnosed CML patients in chronic phase who started TKI therapy in the period from August 2005 to December 2019, 69 patients had available clinical data and transcript type. Transcript type was determined with reverse transcription PCR (RT-PCR) using peripheral blood at diagnosis, as described previously (Branford and Hughes, 2006). Patients were categorised based on the transcript type into e13a2, e14a2, and atypical. Standard patients' variables were collected including TKI treatment (imatinib and/or nilotinib), OS, CCyR, MMR, MR4 and MR5. Survival probabilities were estimated using the Kaplan-Meier method and compared using the log-rank test.

Results

We analysed 69 patients with median follow-up of 74 months. Three patients died (one patient had e13a2, one had e14a2 and one had both). Regarding transcript type, 29 patients (42%) had e13a2, 38 patients (55%) had e14a2, 1 patient (1.5%) had both transcripts, and 1 patient (1.5%) e1a2/e14a2. Patients with e13a2 transcript were on imatinib (37%), nilotinib (48%), and 15% of patients switched from imatinib to nilotinib. Patients with e14a2 were on imatinib (50%), nilotinib (31%), and 19% of patients switched. The patient with both transcripts switched from imatinib to nilotinib. The patient with atypical transcript e1a2/e14a2 was treated with first-line nilotinib. At 100 months, overall survival was not significantly different between e13a2 vs. 14a2 group (100% vs. 95%, p=0.54). Regarding CCyR at 60 months, there was no significant difference between transcript types (100% in e13a2 group vs. 85% in e14a2 group, p=0.11). Regarding MMR at 60 months, there was no significant difference between transcript types (91% in e13a2 group vs. 84% in e14a2 group, p=0.61). No significant difference was found in achievement of MR4 or MR5 in analysed patients.

Conclusion
Our study showed that BCR-ABL1 transcript type was not associated with differences in overall survival, the achievement of CCyR, MMR, nor deep molecular responses in CML patients in Bosnia.

Session topic: 08. Chronic myeloid leukemia - Clinical

Keyword(s): BCR-ABL, Chronic myeloid leukemia, Clinical outcome, Molecular response

Abstract: PB1963

Type: Publication Only

Background

Chronic myeloid leukaemia (CML) is a clonal disease of the haematopoietic stem cells that is driven by the chimeric BCR-ABL1 protein with aberrant tyrosine kinase activity. Chimeric BCR-ABL1 p210 protein results from several types of transcripts, where e13a2 and e14a2 account for the vast majority of cases.

Aims

We analysed the correlation between BCR-ABL1 transcript type and overall survival, the probability of achieving CCyR (complete cytogenetic response), MMR (major molecular response), and deep molecular response (MR4 and MR5). 

Methods

Out of 245 newly diagnosed CML patients in chronic phase who started TKI therapy in the period from August 2005 to December 2019, 69 patients had available clinical data and transcript type. Transcript type was determined with reverse transcription PCR (RT-PCR) using peripheral blood at diagnosis, as described previously (Branford and Hughes, 2006). Patients were categorised based on the transcript type into e13a2, e14a2, and atypical. Standard patients' variables were collected including TKI treatment (imatinib and/or nilotinib), OS, CCyR, MMR, MR4 and MR5. Survival probabilities were estimated using the Kaplan-Meier method and compared using the log-rank test.

Results

We analysed 69 patients with median follow-up of 74 months. Three patients died (one patient had e13a2, one had e14a2 and one had both). Regarding transcript type, 29 patients (42%) had e13a2, 38 patients (55%) had e14a2, 1 patient (1.5%) had both transcripts, and 1 patient (1.5%) e1a2/e14a2. Patients with e13a2 transcript were on imatinib (37%), nilotinib (48%), and 15% of patients switched from imatinib to nilotinib. Patients with e14a2 were on imatinib (50%), nilotinib (31%), and 19% of patients switched. The patient with both transcripts switched from imatinib to nilotinib. The patient with atypical transcript e1a2/e14a2 was treated with first-line nilotinib. At 100 months, overall survival was not significantly different between e13a2 vs. 14a2 group (100% vs. 95%, p=0.54). Regarding CCyR at 60 months, there was no significant difference between transcript types (100% in e13a2 group vs. 85% in e14a2 group, p=0.11). Regarding MMR at 60 months, there was no significant difference between transcript types (91% in e13a2 group vs. 84% in e14a2 group, p=0.61). No significant difference was found in achievement of MR4 or MR5 in analysed patients.

Conclusion
Our study showed that BCR-ABL1 transcript type was not associated with differences in overall survival, the achievement of CCyR, MMR, nor deep molecular responses in CML patients in Bosnia.

Session topic: 08. Chronic myeloid leukemia - Clinical

Keyword(s): BCR-ABL, Chronic myeloid leukemia, Clinical outcome, Molecular response

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