CDKN2A/P16INK4A DELETION IS NOT A POOR PROGNOSIS PREDICTOR IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS TREATED ACCORDING TO PROTOCOL RALL-2009
(Abstract release date: 05/18/17)
EHA Library. Piskunova I. 05/18/17; 182329; PB1615
Inga Piskunova
Contributions
Contributions
Abstract
Abstract: PB1615
Type: Publication Only
Background
CDKN2A/p16INK4a deletion is a frequent cytogenetic abnormality in acute lymphoblastic leukemia (ALL), ranging from 18% to 45%. In pediatric group of patient’s p16INK4a deletion was associated with T-cell ALL phenotype and poor event-free survival. The prognostic impact of CDKN2A/p16INK4a deletion in adult ALL patients appear controversial.
Aims
To evaluate the prognostic impact of the CDKN2A/p16INK4a deletion in adult patients with acute lymphoblastic leukemia.
Methods
We present the results of the CDKN2A/p16INK4a deletion in 110 adult patients with newly diagnosed Philadelphia –negative ALL, which were treated by RALL-2009 (NCT01193933) in our center since June 2009 till September 2016. Patients characteristics: the median of age was 26 years old (range 15 -54), the median white blood cell (WBC) count was 16.9×109 /L (range: 0.4-785×109 /L), the median blasts cells count in the bone marrow (BM) was 84.4 % (range: 0-98). Sixty-five (59 %) of the 110 patients had a B-cell phenotype, 42 (38 %) had a T-cell phenotype, 3 (2.7%) patients - biphenotypical ALL. Interphase fluorescence in situ hybridization (FISH) was performed for detection CDKN2A deletion, TEL/AML1, MLL rearrangement, MYC (8q24.21) translocation, ТР53 deletion, iAMP21.
Results
The prevalence of the CDKN2A deletion in all studied population was 24,5 % (27 cases). The frequency of homozygous deletions was 70% (in 19 cases), heterozygous deletion was 30 % (in 8 cases). CDKN2A deletion was detected in 14 (52%) patients with precursor-B phenotype, in 11 cases (41%) with T-ALL and in 2 (7%) cases with biphenotypical ALL. Our study demonstrated that CDKN2A deletion had no significant association with age, sex, WBC counts, BM blasts, risk stratification groups, complete remission (CR) and relapse rate in B-cell ALL. We didn’t reveal any significant differences in OS, clinical and laboratory dates between groups of patients with homozygous and heterozygous deletion of the CDKN2A deletion.
The analysis for T-ALL has detected that CDKN2A deletion was strongly associated with high WBC count (the median is 86×10 /L, p=0.006), with high lactate dehydrogenase (LDH) level (the median is 3062 E/L, p=0.0004) and no assonating with CR and replace incidence was found. We didn’t revealed relationship between CDKN2A deletion and MLL, TEL/AML1 rearrangement, MYC translocation, ТР53 mutation and iAMP21.
CDKN2A deletion didn’t have statistically significant impact on outcome of patients. The five-year overall survival (OS) for patients with and without deletion was 84% and 77% (p=0, 40); free survival (DFS) was 91% и 71 % (p=0, 09), respectively. OS for patients with B-cell ALL with and without deletion was 85% and 76 % (p=0, 35); DFS was 92% and 65 % (p=0, 07), respectively. OS for T-cell ALL patients with and without deletion was 90 % and 80 % (p=0, 63); DFS was 100 % and 82 % (p=0, 24), respectively. (Figure 1)
Conclusion
We were unable to demonstrate prognostic value of the CDKN2A deletion in adult ALL patients and did not find significant association between deletion of the CDKN2A gene and with known cytogenetic prognostic factors. However patients with T-cell ALL and CDKN2A deletion had a more aggressive initial clinical features (high level WBC and LDH), but it didn’t associate with poor outcomes including overall survival.Deletion of CDKN2A is not adverse prognostic factor in adult ALL treated according to protocol RALL-2009.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): FISH, Cytogenetics, Acute lymphoblastic leukemia
Abstract: PB1615
Type: Publication Only
Background
CDKN2A/p16INK4a deletion is a frequent cytogenetic abnormality in acute lymphoblastic leukemia (ALL), ranging from 18% to 45%. In pediatric group of patient’s p16INK4a deletion was associated with T-cell ALL phenotype and poor event-free survival. The prognostic impact of CDKN2A/p16INK4a deletion in adult ALL patients appear controversial.
Aims
To evaluate the prognostic impact of the CDKN2A/p16INK4a deletion in adult patients with acute lymphoblastic leukemia.
Methods
We present the results of the CDKN2A/p16INK4a deletion in 110 adult patients with newly diagnosed Philadelphia –negative ALL, which were treated by RALL-2009 (NCT01193933) in our center since June 2009 till September 2016. Patients characteristics: the median of age was 26 years old (range 15 -54), the median white blood cell (WBC) count was 16.9×109 /L (range: 0.4-785×109 /L), the median blasts cells count in the bone marrow (BM) was 84.4 % (range: 0-98). Sixty-five (59 %) of the 110 patients had a B-cell phenotype, 42 (38 %) had a T-cell phenotype, 3 (2.7%) patients - biphenotypical ALL. Interphase fluorescence in situ hybridization (FISH) was performed for detection CDKN2A deletion, TEL/AML1, MLL rearrangement, MYC (8q24.21) translocation, ТР53 deletion, iAMP21.
Results
The prevalence of the CDKN2A deletion in all studied population was 24,5 % (27 cases). The frequency of homozygous deletions was 70% (in 19 cases), heterozygous deletion was 30 % (in 8 cases). CDKN2A deletion was detected in 14 (52%) patients with precursor-B phenotype, in 11 cases (41%) with T-ALL and in 2 (7%) cases with biphenotypical ALL. Our study demonstrated that CDKN2A deletion had no significant association with age, sex, WBC counts, BM blasts, risk stratification groups, complete remission (CR) and relapse rate in B-cell ALL. We didn’t reveal any significant differences in OS, clinical and laboratory dates between groups of patients with homozygous and heterozygous deletion of the CDKN2A deletion.
The analysis for T-ALL has detected that CDKN2A deletion was strongly associated with high WBC count (the median is 86×10 /L, p=0.006), with high lactate dehydrogenase (LDH) level (the median is 3062 E/L, p=0.0004) and no assonating with CR and replace incidence was found. We didn’t revealed relationship between CDKN2A deletion and MLL, TEL/AML1 rearrangement, MYC translocation, ТР53 mutation and iAMP21.
CDKN2A deletion didn’t have statistically significant impact on outcome of patients. The five-year overall survival (OS) for patients with and without deletion was 84% and 77% (p=0, 40); free survival (DFS) was 91% и 71 % (p=0, 09), respectively. OS for patients with B-cell ALL with and without deletion was 85% and 76 % (p=0, 35); DFS was 92% and 65 % (p=0, 07), respectively. OS for T-cell ALL patients with and without deletion was 90 % and 80 % (p=0, 63); DFS was 100 % and 82 % (p=0, 24), respectively. (Figure 1)
Conclusion
We were unable to demonstrate prognostic value of the CDKN2A deletion in adult ALL patients and did not find significant association between deletion of the CDKN2A gene and with known cytogenetic prognostic factors. However patients with T-cell ALL and CDKN2A deletion had a more aggressive initial clinical features (high level WBC and LDH), but it didn’t associate with poor outcomes including overall survival.Deletion of CDKN2A is not adverse prognostic factor in adult ALL treated according to protocol RALL-2009.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): FISH, Cytogenetics, Acute lymphoblastic leukemia
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