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COMPLEX ADDITIONAL CHROMOSOME ABERRATIONS IN PH-POSITIVE CELLS IMPACT ON CHRONIC MYELOID LEUKEMIA PATIENTS’ SURVIVAL IN THE ERA OF TYROSINE KINASE INHIBITORS
Author(s):
Mikhail Fominykh
,
Mikhail Fominykh
Affiliations:
Clinical department,Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
Oleg Shuhov
,
Oleg Shuhov
Affiliations:
Clinical department,National Research Center for Hematology,Moscow,Russian Federation
Irina Martynkevich
,
Irina Martynkevich
Affiliations:
Clinical department,Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
Vasily Shuvaev
,
Vasily Shuvaev
Affiliations:
Clinical department,Russian Research Institute of Hematology and Transfusiology,Saint-Petersburg,Russian Federation
Ekaterina Chelysheva
,
Ekaterina Chelysheva
Affiliations:
Clinical department,National Research Center for Hematology,Moscow,Russian Federation
Anna Turkina
Anna Turkina
Affiliations:
Clinical department,National Research Center for Hematology,Moscow,Russian Federation
(Abstract release date: 05/18/17) EHA Library. Fomin A. 05/18/17; 182535; PB1821
Dr. Aleksandr Fomin
Dr. Aleksandr Fomin
Contributions
PDF Abstract
Abstract

Abstract: PB1821

Type: Publication Only

Background
Additional chromosomal aberrations (ACA) as marker of clonal evolution in chronic myeloid leukemia (CML) patients were previously noted in association with resistance to therapy. The presents of ACA have been associated with a worse prognosis for survival in the pre-TKI era. The ACA classification proposed earlier was based only on its frequencies. Whereas ACA’s clinical impact had not yet been clearly established.

Aims

The aim of our study was to evaluate the long-term impact of the ACA presence in Ph-positive cells in CML patients on TKI treatment results.

Methods

30 patients with ACA in Ph-positive cells treated in our center from 2005 to 2015 years were included in this study. Cytogenetic analyses of at least 20 Giemsa-banded bone marrow metaphases were interpreted per ISCN 2013.
We analyzed overall survival (OS) and cumulative incidence of CML-related death on TKI treatment. Cox regression was used for multivariate survival analysis, that included next covariates: number of ACA, type of ACA, age, TKI type, CP or AP at diagnosis. OS was estimated by Kaplan-Meier method with log-rank test for comparison. Cumulative incidence of CML-related death was estimated into consideration the presents of competing risks (CML-unrelated death) using Gray’s test for comparison between groups.

Results

Median follow-up period in ACA group (n=30) was 51 months (3-124). ACA at diagnosis were detected in 16 (53%) of 30 patients. Chronic phase CML at diagnosis was determined in 23 (77%) patients. Imatinib was used as first-line in 20 (67%) patients, 3 (10%) patients were initially treated with Nilotinib. Accelerated phase was defined in 7 (23%) patients. In that group treatment of 6 patients was started with Imatinib and Dasatinib was given initially for one patient.
«Major-route» ACAs (trisomy 8, +der(22)t(9;22)(q34;q11), i(17)(q10), trisomy 19,) were detected in 16 (53%) of 30 patients. Complex aberrations (2 ACA and more) were revealed in 7 (23%) patients, 4 patients from this group had «major-route» ACA.
10-years OS in the whole ACA group was 67%, 10-years cumulative incidence of CML-related death was 23%.
Number of ACA (p=0.03, HR=13.2) and age (p=0.03, HR=1.14) had statistical significance influence on survival by regression analysis.
10-years OS was 31% and 77% (p<0.05) in patients with complex ACA and single ACA respectively, 10-years cumulative incidence of CML-related death was 54% for patients with complex aberrations versus 10% for single ACA patients (p<0.05) (Figure 1).

Conclusion
Our results showed that TKI treated CML patients with complex ACAs have a higher risk of progression and death in comparison with single-ACA patients.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Tyrosine kinase inhibitor, Cytogenetic abnormalities, Chronic myeloid leukemia, Chromosomal abnormality

Abstract: PB1821

Type: Publication Only

Background
Additional chromosomal aberrations (ACA) as marker of clonal evolution in chronic myeloid leukemia (CML) patients were previously noted in association with resistance to therapy. The presents of ACA have been associated with a worse prognosis for survival in the pre-TKI era. The ACA classification proposed earlier was based only on its frequencies. Whereas ACA’s clinical impact had not yet been clearly established.

Aims

The aim of our study was to evaluate the long-term impact of the ACA presence in Ph-positive cells in CML patients on TKI treatment results.

Methods

30 patients with ACA in Ph-positive cells treated in our center from 2005 to 2015 years were included in this study. Cytogenetic analyses of at least 20 Giemsa-banded bone marrow metaphases were interpreted per ISCN 2013.
We analyzed overall survival (OS) and cumulative incidence of CML-related death on TKI treatment. Cox regression was used for multivariate survival analysis, that included next covariates: number of ACA, type of ACA, age, TKI type, CP or AP at diagnosis. OS was estimated by Kaplan-Meier method with log-rank test for comparison. Cumulative incidence of CML-related death was estimated into consideration the presents of competing risks (CML-unrelated death) using Gray’s test for comparison between groups.

Results

Median follow-up period in ACA group (n=30) was 51 months (3-124). ACA at diagnosis were detected in 16 (53%) of 30 patients. Chronic phase CML at diagnosis was determined in 23 (77%) patients. Imatinib was used as first-line in 20 (67%) patients, 3 (10%) patients were initially treated with Nilotinib. Accelerated phase was defined in 7 (23%) patients. In that group treatment of 6 patients was started with Imatinib and Dasatinib was given initially for one patient.
«Major-route» ACAs (trisomy 8, +der(22)t(9;22)(q34;q11), i(17)(q10), trisomy 19,) were detected in 16 (53%) of 30 patients. Complex aberrations (2 ACA and more) were revealed in 7 (23%) patients, 4 patients from this group had «major-route» ACA.
10-years OS in the whole ACA group was 67%, 10-years cumulative incidence of CML-related death was 23%.
Number of ACA (p=0.03, HR=13.2) and age (p=0.03, HR=1.14) had statistical significance influence on survival by regression analysis.
10-years OS was 31% and 77% (p<0.05) in patients with complex ACA and single ACA respectively, 10-years cumulative incidence of CML-related death was 54% for patients with complex aberrations versus 10% for single ACA patients (p<0.05) (Figure 1).

Conclusion
Our results showed that TKI treated CML patients with complex ACAs have a higher risk of progression and death in comparison with single-ACA patients.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Tyrosine kinase inhibitor, Cytogenetic abnormalities, Chronic myeloid leukemia, Chromosomal abnormality

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