Contributions
Abstract: EP336
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
Copy number variation (CNV) of IKZF1, RB1, EBF1 genes and/or PAR1 region in childhood acute lymphoblastic leukemia B (B-ALL) confers a worse prognosis, with event-free survival (EFS) at 10 years of 68%. Recently, a new classification has been proposed to stratify pediatric patients with B-ALL according to cytogenetic alterations and CNV, defining four risk groups with prognostic impact.
Aims
The aim of this study has been to determine if CNV can change the prognosis determined by cytogenetic alterations in a series of pediatric patients with B-ALL.
Methods
We perform a retrospective analysis of CNV in 106 patients diagnosed with B-ALL in our hospital between January-2014 and January-2021, included in the ALL/SEHOP-PETHEMA 2013 therapeutic recommendation guidelines. We use SALSA MLPA P335 kit (MRC Holland), which includes probes for IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1 and PAR1 (CRLF2 and P2RY8).
Results
Of the 106 cases, 55 were included in the study as they fulfilled the criteria to perform the MLPA (≥30% blasts in bone marrow and high-quality DNA). The clinical-biological characteristics are detailed in Table 1. The genes that were deleted with the highest prevalence were: ETV6 (43%), PAX5 (27%), CDKN2A/B (27%) and IKZF1 (18%). CNV was not observed in 24% of the cases, while 26%, 16% and 34% showed 1, 2 or ≥3 CNV, respectively.
Good risk CNV profile (CNV-GR) was presented in 53% of the cases, 25 had good risk cytogenetics (CYT-GR) (45%), four intermediate risk cytogenetics (CYT-IR) (7%) and any patient showed poor risk cytogenetics (CYT-PR). Poor risk CNV (CNV-PR) was observed in 31% of the cases, of them, six patients had CYT-GR (11%), ten had CYT-IR (18%) and one had CYT-PR (2%). Age ≥10 years, phenotype, intermediate and poor cytogenetic risk, not achieving complete remission, relapse and lower EFS occurred more frequently in the CNV-PR group, with significant differences (Table 1). The 4-years EFS was 100% for CNV-GR, 80% for CNV-IR and 38% for CNV-PR.
Of the 55 patients, six relapsed, all of them within the good or intermediate cytogenetic group; five with CNV-PR and one with CNV-IR. Three cases had CRLF2 rearrangements and a CNV profile with IKZF1, CDKN2A and CDKN2B deletions, among others. One case had a complex karyotype with PAX5 rearrangement and a CNV-IR profile with CDKN2A/B biallelic deletion and PAX5 deletion. Another patient had high hyperdiplod karyotype and an isolated IKZF1 deletion. Finally, the last case had a complex karyotype with t(1;19) and a CNV-PR profile with deletion of PAX5 and RB1. All of them were treated according to the ALL/SEHOP-PETHEMA 2013 protocol, five within the high-risk group and one in the good risk group.
Conclusion
Despite it is a small cohort, the results confirm that the combination of conventional cytogenetic risk and CNV analysis allows a better classification of the biological risk of the disease. We can identify a group with a very good prognosis (CYT-GR and CNV-GR) with 4-years EFS of 100% and a group with higher probability of relapse (CYT-GR/IR and CNV-PR) with 4-years EFS of 38%.
Keyword(s): B cell acute lymphoblastic leukemia, Gene deletion, Ikaros, Molecular cytogenetics
Abstract: EP336
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
Copy number variation (CNV) of IKZF1, RB1, EBF1 genes and/or PAR1 region in childhood acute lymphoblastic leukemia B (B-ALL) confers a worse prognosis, with event-free survival (EFS) at 10 years of 68%. Recently, a new classification has been proposed to stratify pediatric patients with B-ALL according to cytogenetic alterations and CNV, defining four risk groups with prognostic impact.
Aims
The aim of this study has been to determine if CNV can change the prognosis determined by cytogenetic alterations in a series of pediatric patients with B-ALL.
Methods
We perform a retrospective analysis of CNV in 106 patients diagnosed with B-ALL in our hospital between January-2014 and January-2021, included in the ALL/SEHOP-PETHEMA 2013 therapeutic recommendation guidelines. We use SALSA MLPA P335 kit (MRC Holland), which includes probes for IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1 and PAR1 (CRLF2 and P2RY8).
Results
Of the 106 cases, 55 were included in the study as they fulfilled the criteria to perform the MLPA (≥30% blasts in bone marrow and high-quality DNA). The clinical-biological characteristics are detailed in Table 1. The genes that were deleted with the highest prevalence were: ETV6 (43%), PAX5 (27%), CDKN2A/B (27%) and IKZF1 (18%). CNV was not observed in 24% of the cases, while 26%, 16% and 34% showed 1, 2 or ≥3 CNV, respectively.
Good risk CNV profile (CNV-GR) was presented in 53% of the cases, 25 had good risk cytogenetics (CYT-GR) (45%), four intermediate risk cytogenetics (CYT-IR) (7%) and any patient showed poor risk cytogenetics (CYT-PR). Poor risk CNV (CNV-PR) was observed in 31% of the cases, of them, six patients had CYT-GR (11%), ten had CYT-IR (18%) and one had CYT-PR (2%). Age ≥10 years, phenotype, intermediate and poor cytogenetic risk, not achieving complete remission, relapse and lower EFS occurred more frequently in the CNV-PR group, with significant differences (Table 1). The 4-years EFS was 100% for CNV-GR, 80% for CNV-IR and 38% for CNV-PR.
Of the 55 patients, six relapsed, all of them within the good or intermediate cytogenetic group; five with CNV-PR and one with CNV-IR. Three cases had CRLF2 rearrangements and a CNV profile with IKZF1, CDKN2A and CDKN2B deletions, among others. One case had a complex karyotype with PAX5 rearrangement and a CNV-IR profile with CDKN2A/B biallelic deletion and PAX5 deletion. Another patient had high hyperdiplod karyotype and an isolated IKZF1 deletion. Finally, the last case had a complex karyotype with t(1;19) and a CNV-PR profile with deletion of PAX5 and RB1. All of them were treated according to the ALL/SEHOP-PETHEMA 2013 protocol, five within the high-risk group and one in the good risk group.
Conclusion
Despite it is a small cohort, the results confirm that the combination of conventional cytogenetic risk and CNV analysis allows a better classification of the biological risk of the disease. We can identify a group with a very good prognosis (CYT-GR and CNV-GR) with 4-years EFS of 100% and a group with higher probability of relapse (CYT-GR/IR and CNV-PR) with 4-years EFS of 38%.
Keyword(s): B cell acute lymphoblastic leukemia, Gene deletion, Ikaros, Molecular cytogenetics