PROGNOSTIC IMPACT OF COPY NUMBER ALTERATIONS IN A SERIES OF PEDIATRIC PATIENTS WITH DE NOVO B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA IN A SINGLE CENTER
(Abstract release date: 05/19/16)
EHA Library. Camós M. 06/09/16; 132415; E866
Mireia Camós
Contributions
Contributions
Abstract
Abstract: E866
Type: Eposter Presentation
Background
gene copy number alterations (CNAs) have been recently proposed as variables for risk stratification in acute lymphoblastic leukemia (ALL). However, their use in clinical practice is controversial, as their prognostic impact could depend on the applied therapeutical protocol and the interaction with other clinical and biological variables.
Aims
to analyze the prognostic impact of CNAs in a series of pediatric patients with B-cell precursor ALL (pre-B ALL) treated in a single center.
Methods
pediatric patients (0-18 years) with pre-B ALL, diagnosed between 1999 and 2015 and homogeneously treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society (SEHOP) Cooperative Group (SHOP-99, SHOP-2005, SEHOP-PETHEMA 2013). CNAs were studied by MLPA technique with SALSA-P335 kit (MRC-Holland) and Coffalyser software.
Results
we included 55 patients with a median age of 4.7 years (range 1.1-14.9), 56% males. Only one patient had central nervous system infiltration. Median WBC count was 8.4 x109/L (range 1.1-296.9). All cytogenetic subtypes were represented. We observed the presence of CNAs in 29 patients (53%), including 17 (31%) cases with one CNA, 8 (15%) patients with 2 CNAs and 4 (7.5%) patients with ≥ 3 CNAs. The most frequent CNAs were deletions of CDKN2A/B, observed in 12 patients (22%), followed by ETV6 deletions in 11 cases (20%) and IKZF1 deletions in 9 cases (16%); also, we observed deletions of PAX5 in 7 cases (13%), of BTG1 in 4 patients (7%), of RB1 in 2 cases (4%), JAK2 deletions in one case and CRLF2 alterations (PAR region) in one case. IKZF1 deletions were more frequently observed in BCR-ABL1 rearranged cases and in patients with B-other subtype (cases with absence of main cytogenetic categories), and ETV6 deletions predominated in cases with ETV6-RUNX1 rearrangement. Among those patients with more than one CNA, IKZF1 was the gene most frequently involved (IKZF1plus, 7 cases). The presence of CNAs was significantly correlated to older age (p=0.006), hyperleukocytosis >20x109/L (p=0.018) and high levels of minimal residual disease (MRD>10%) at day 15 of induction, assessed by flow cytometry (p=0.012). A higher number of CNAs (≥2) was found in boys (p=0.026). Noticeably, the patient with CNS infiltration harbored 3 CNAs. IKZF1 deletions were associated with high hyperleukocytosis (>100 x109/L, p=0.001), older age (p=0.001), high NCI risk (p=0.008) and high MRD levels at day 15 (p<0.0001). We found the same associations for IKZF1plus. CDKN2A/B deletions showed a trend to high WBC count (>100 x109/L, p=0.051) and presence of MRD at the end of induction (MRD>0.01%, p=0.082). We found no significant associations for ETV6 or PAX5 deletions. After a median follow up 2.6 years (0.3-11.9) all patients are alive and 3 patients relapsed, with an event free survival (EFS) at 5 years of 87±7%. The presence of ≥ 2 CNAs correlated to worse EFS (64±16% vs 100%, p=0.043).
Conclusion
in our series, the presence of CNAs, mainly IKZF1 deletions, were associated with poor prognostic factors like older age, high WBC count and high levels of MRD at early timepoints. We are currently expanding our series to confirm our results. GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Ikaros, Pediatric, Prognostic factor
Type: Eposter Presentation
Background
gene copy number alterations (CNAs) have been recently proposed as variables for risk stratification in acute lymphoblastic leukemia (ALL). However, their use in clinical practice is controversial, as their prognostic impact could depend on the applied therapeutical protocol and the interaction with other clinical and biological variables.
Aims
to analyze the prognostic impact of CNAs in a series of pediatric patients with B-cell precursor ALL (pre-B ALL) treated in a single center.
Methods
pediatric patients (0-18 years) with pre-B ALL, diagnosed between 1999 and 2015 and homogeneously treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society (SEHOP) Cooperative Group (SHOP-99, SHOP-2005, SEHOP-PETHEMA 2013). CNAs were studied by MLPA technique with SALSA-P335 kit (MRC-Holland) and Coffalyser software.
Results
we included 55 patients with a median age of 4.7 years (range 1.1-14.9), 56% males. Only one patient had central nervous system infiltration. Median WBC count was 8.4 x109/L (range 1.1-296.9). All cytogenetic subtypes were represented. We observed the presence of CNAs in 29 patients (53%), including 17 (31%) cases with one CNA, 8 (15%) patients with 2 CNAs and 4 (7.5%) patients with ≥ 3 CNAs. The most frequent CNAs were deletions of CDKN2A/B, observed in 12 patients (22%), followed by ETV6 deletions in 11 cases (20%) and IKZF1 deletions in 9 cases (16%); also, we observed deletions of PAX5 in 7 cases (13%), of BTG1 in 4 patients (7%), of RB1 in 2 cases (4%), JAK2 deletions in one case and CRLF2 alterations (PAR region) in one case. IKZF1 deletions were more frequently observed in BCR-ABL1 rearranged cases and in patients with B-other subtype (cases with absence of main cytogenetic categories), and ETV6 deletions predominated in cases with ETV6-RUNX1 rearrangement. Among those patients with more than one CNA, IKZF1 was the gene most frequently involved (IKZF1plus, 7 cases). The presence of CNAs was significantly correlated to older age (p=0.006), hyperleukocytosis >20x109/L (p=0.018) and high levels of minimal residual disease (MRD>10%) at day 15 of induction, assessed by flow cytometry (p=0.012). A higher number of CNAs (≥2) was found in boys (p=0.026). Noticeably, the patient with CNS infiltration harbored 3 CNAs. IKZF1 deletions were associated with high hyperleukocytosis (>100 x109/L, p=0.001), older age (p=0.001), high NCI risk (p=0.008) and high MRD levels at day 15 (p<0.0001). We found the same associations for IKZF1plus. CDKN2A/B deletions showed a trend to high WBC count (>100 x109/L, p=0.051) and presence of MRD at the end of induction (MRD>0.01%, p=0.082). We found no significant associations for ETV6 or PAX5 deletions. After a median follow up 2.6 years (0.3-11.9) all patients are alive and 3 patients relapsed, with an event free survival (EFS) at 5 years of 87±7%. The presence of ≥ 2 CNAs correlated to worse EFS (64±16% vs 100%, p=0.043).
Conclusion
in our series, the presence of CNAs, mainly IKZF1 deletions, were associated with poor prognostic factors like older age, high WBC count and high levels of MRD at early timepoints. We are currently expanding our series to confirm our results. GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Ikaros, Pediatric, Prognostic factor
Abstract: E866
Type: Eposter Presentation
Background
gene copy number alterations (CNAs) have been recently proposed as variables for risk stratification in acute lymphoblastic leukemia (ALL). However, their use in clinical practice is controversial, as their prognostic impact could depend on the applied therapeutical protocol and the interaction with other clinical and biological variables.
Aims
to analyze the prognostic impact of CNAs in a series of pediatric patients with B-cell precursor ALL (pre-B ALL) treated in a single center.
Methods
pediatric patients (0-18 years) with pre-B ALL, diagnosed between 1999 and 2015 and homogeneously treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society (SEHOP) Cooperative Group (SHOP-99, SHOP-2005, SEHOP-PETHEMA 2013). CNAs were studied by MLPA technique with SALSA-P335 kit (MRC-Holland) and Coffalyser software.
Results
we included 55 patients with a median age of 4.7 years (range 1.1-14.9), 56% males. Only one patient had central nervous system infiltration. Median WBC count was 8.4 x109/L (range 1.1-296.9). All cytogenetic subtypes were represented. We observed the presence of CNAs in 29 patients (53%), including 17 (31%) cases with one CNA, 8 (15%) patients with 2 CNAs and 4 (7.5%) patients with ≥ 3 CNAs. The most frequent CNAs were deletions of CDKN2A/B, observed in 12 patients (22%), followed by ETV6 deletions in 11 cases (20%) and IKZF1 deletions in 9 cases (16%); also, we observed deletions of PAX5 in 7 cases (13%), of BTG1 in 4 patients (7%), of RB1 in 2 cases (4%), JAK2 deletions in one case and CRLF2 alterations (PAR region) in one case. IKZF1 deletions were more frequently observed in BCR-ABL1 rearranged cases and in patients with B-other subtype (cases with absence of main cytogenetic categories), and ETV6 deletions predominated in cases with ETV6-RUNX1 rearrangement. Among those patients with more than one CNA, IKZF1 was the gene most frequently involved (IKZF1plus, 7 cases). The presence of CNAs was significantly correlated to older age (p=0.006), hyperleukocytosis >20x109/L (p=0.018) and high levels of minimal residual disease (MRD>10%) at day 15 of induction, assessed by flow cytometry (p=0.012). A higher number of CNAs (≥2) was found in boys (p=0.026). Noticeably, the patient with CNS infiltration harbored 3 CNAs. IKZF1 deletions were associated with high hyperleukocytosis (>100 x109/L, p=0.001), older age (p=0.001), high NCI risk (p=0.008) and high MRD levels at day 15 (p<0.0001). We found the same associations for IKZF1plus. CDKN2A/B deletions showed a trend to high WBC count (>100 x109/L, p=0.051) and presence of MRD at the end of induction (MRD>0.01%, p=0.082). We found no significant associations for ETV6 or PAX5 deletions. After a median follow up 2.6 years (0.3-11.9) all patients are alive and 3 patients relapsed, with an event free survival (EFS) at 5 years of 87±7%. The presence of ≥ 2 CNAs correlated to worse EFS (64±16% vs 100%, p=0.043).
Conclusion
in our series, the presence of CNAs, mainly IKZF1 deletions, were associated with poor prognostic factors like older age, high WBC count and high levels of MRD at early timepoints. We are currently expanding our series to confirm our results. GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Ikaros, Pediatric, Prognostic factor
Type: Eposter Presentation
Background
gene copy number alterations (CNAs) have been recently proposed as variables for risk stratification in acute lymphoblastic leukemia (ALL). However, their use in clinical practice is controversial, as their prognostic impact could depend on the applied therapeutical protocol and the interaction with other clinical and biological variables.
Aims
to analyze the prognostic impact of CNAs in a series of pediatric patients with B-cell precursor ALL (pre-B ALL) treated in a single center.
Methods
pediatric patients (0-18 years) with pre-B ALL, diagnosed between 1999 and 2015 and homogeneously treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society (SEHOP) Cooperative Group (SHOP-99, SHOP-2005, SEHOP-PETHEMA 2013). CNAs were studied by MLPA technique with SALSA-P335 kit (MRC-Holland) and Coffalyser software.
Results
we included 55 patients with a median age of 4.7 years (range 1.1-14.9), 56% males. Only one patient had central nervous system infiltration. Median WBC count was 8.4 x109/L (range 1.1-296.9). All cytogenetic subtypes were represented. We observed the presence of CNAs in 29 patients (53%), including 17 (31%) cases with one CNA, 8 (15%) patients with 2 CNAs and 4 (7.5%) patients with ≥ 3 CNAs. The most frequent CNAs were deletions of CDKN2A/B, observed in 12 patients (22%), followed by ETV6 deletions in 11 cases (20%) and IKZF1 deletions in 9 cases (16%); also, we observed deletions of PAX5 in 7 cases (13%), of BTG1 in 4 patients (7%), of RB1 in 2 cases (4%), JAK2 deletions in one case and CRLF2 alterations (PAR region) in one case. IKZF1 deletions were more frequently observed in BCR-ABL1 rearranged cases and in patients with B-other subtype (cases with absence of main cytogenetic categories), and ETV6 deletions predominated in cases with ETV6-RUNX1 rearrangement. Among those patients with more than one CNA, IKZF1 was the gene most frequently involved (IKZF1plus, 7 cases). The presence of CNAs was significantly correlated to older age (p=0.006), hyperleukocytosis >20x109/L (p=0.018) and high levels of minimal residual disease (MRD>10%) at day 15 of induction, assessed by flow cytometry (p=0.012). A higher number of CNAs (≥2) was found in boys (p=0.026). Noticeably, the patient with CNS infiltration harbored 3 CNAs. IKZF1 deletions were associated with high hyperleukocytosis (>100 x109/L, p=0.001), older age (p=0.001), high NCI risk (p=0.008) and high MRD levels at day 15 (p<0.0001). We found the same associations for IKZF1plus. CDKN2A/B deletions showed a trend to high WBC count (>100 x109/L, p=0.051) and presence of MRD at the end of induction (MRD>0.01%, p=0.082). We found no significant associations for ETV6 or PAX5 deletions. After a median follow up 2.6 years (0.3-11.9) all patients are alive and 3 patients relapsed, with an event free survival (EFS) at 5 years of 87±7%. The presence of ≥ 2 CNAs correlated to worse EFS (64±16% vs 100%, p=0.043).
Conclusion
in our series, the presence of CNAs, mainly IKZF1 deletions, were associated with poor prognostic factors like older age, high WBC count and high levels of MRD at early timepoints. We are currently expanding our series to confirm our results. GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Ikaros, Pediatric, Prognostic factor
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