PREDICTIVE VALUE OF IG/TR AND BCR/ABL1 PCR-BASED MINIMAL RESIDUAL DISEASE MONITORING IN PH+ PEDIATRIC ALL TREATED WITH IMATINIB IN THE ESPHALL STUDY,
(Abstract release date: 05/19/16)
EHA Library. Cazzaniga G. 06/09/16; 135350; LB2239
Disclosure(s): Nothing to disclose
Dr. Giovanni Cazzaniga
Contributions
Contributions
Abstract
Abstract: LB2239
Type: Eposter Presentation
Background
Several studies showed that minimal residual disease (MRD) detection is a strong independent prognostic factor in childhood acute lymphoblastic leukemia (ALL) including Ph+ ALL treated with conventional chemotherapy. Very few data and of difficult interpretation are available on the predictive value of early MRD response in Ph+ ALL treated with tyrosine kinase inhibitors (TKI)s.
Aims
MRD was detected by real-time quantitative PCR of rearranged immunoglobulin/T-cell receptor (IG/TR) genes and/or BCR/ABL1 fusion transcript in the EsPhALL study to investigate its predictive value in patients treated with imatinib.
Methods
In the EsPhALL study, after induction therapy, patients received BFM high risk ALL therapy; imatinib was given intermittently during the intensive treatment phases for a total of 18 weeks or less, usually 10 weeks, if patients underwent hematopoietic stem cell transplantation (HSCT), indicated for large majority of patients. MRD on the bone marrow (BM) was monitored as an ancillary study after induction therapy (TP1), consolidation Phase IB (TP2), HR Block1 (TP3), HR Block2 (TP4), HR Block3, first and second reinduction, and at end of therapy. Quantitative PCR analysis was performed and interpreted according to Euro-MRD network guidelines for both IG/TR and BCR/ABL1.
Results
MRD negativity increases progressively, both by IG/TR (from 10% at TP1 to 57% at TP4) and by BCR/ABL1 (from 13% at TP1 to 30% at TP4). Conversely, the proportion of patients with highly positive MRD by IG/TR decreases from 78% at TP1 to 14% at TP4 and by BCR/ABL1, from 80% at TP1 to 57% only at TP4. The minority of patients IG/TR MRD negative at TP1 (N=9, 10%) had a very favorable outcome with no relapses, whereas patients with high or low MRD positivity had a similarly high 5-year cumulative incidence of relapse (CIR) (SE) of 35.2 (5.9) and 36.4 (15.4), respectively. Achieving MRD negativity at TP2 is also associated with low risk of relapse (5-year CIR (SE) 14.3 (9.8)), whereas achieving negativity only at TP3 or TP4 is associated with a CIR of 36.4 (15.5) and 42.9 (21.6), respectively, similar to that of patients with low or high positivity at any time-point. BCR/ABL1 MRD negativity (although based on small numbers) at TP1 or TP2 is reached less frequently compared with IG/TR MRD, but is associated with a similar very low risk of relapse (one relapse in 8 patients MRD negative at TP1), while patients with low or high positivity have instead a high risk of relapse, again similar to that observed for positive IG/TR MRD. The overall concordance between the two methods is 69%; for patients with positive MRD by both techniques, the estimated mean differences of BCR/ABL1 versus IG/TR results were significantly different from zero, and were consistent according to different TPs with significantly higher positivity by BCR/ABL1. There are also rare cases consistently negative by IG/TR and positive by BCR/ABL1 with a very favorable outcome.
Conclusion
MRD negativity by IG/TR is obtained more frequently than by BCR/ABL1 and it is highly predictive of a very favorable outcome and the earlier the negativity, the better the prognosis. Further investigations are needed to understand the biology in cases with discordant results, and in particular of those negative by IG/TR and positive by BCR/ABL1. The role of MRD in patients treated continuously with TKI inhibitors and without HSCT needs to be explored in current studies.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, BCR-ABL, Minimal residual disease (MRD), Pediatric
Type: Eposter Presentation
Background
Several studies showed that minimal residual disease (MRD) detection is a strong independent prognostic factor in childhood acute lymphoblastic leukemia (ALL) including Ph+ ALL treated with conventional chemotherapy. Very few data and of difficult interpretation are available on the predictive value of early MRD response in Ph+ ALL treated with tyrosine kinase inhibitors (TKI)s.
Aims
MRD was detected by real-time quantitative PCR of rearranged immunoglobulin/T-cell receptor (IG/TR) genes and/or BCR/ABL1 fusion transcript in the EsPhALL study to investigate its predictive value in patients treated with imatinib.
Methods
In the EsPhALL study, after induction therapy, patients received BFM high risk ALL therapy; imatinib was given intermittently during the intensive treatment phases for a total of 18 weeks or less, usually 10 weeks, if patients underwent hematopoietic stem cell transplantation (HSCT), indicated for large majority of patients. MRD on the bone marrow (BM) was monitored as an ancillary study after induction therapy (TP1), consolidation Phase IB (TP2), HR Block1 (TP3), HR Block2 (TP4), HR Block3, first and second reinduction, and at end of therapy. Quantitative PCR analysis was performed and interpreted according to Euro-MRD network guidelines for both IG/TR and BCR/ABL1.
Results
MRD negativity increases progressively, both by IG/TR (from 10% at TP1 to 57% at TP4) and by BCR/ABL1 (from 13% at TP1 to 30% at TP4). Conversely, the proportion of patients with highly positive MRD by IG/TR decreases from 78% at TP1 to 14% at TP4 and by BCR/ABL1, from 80% at TP1 to 57% only at TP4. The minority of patients IG/TR MRD negative at TP1 (N=9, 10%) had a very favorable outcome with no relapses, whereas patients with high or low MRD positivity had a similarly high 5-year cumulative incidence of relapse (CIR) (SE) of 35.2 (5.9) and 36.4 (15.4), respectively. Achieving MRD negativity at TP2 is also associated with low risk of relapse (5-year CIR (SE) 14.3 (9.8)), whereas achieving negativity only at TP3 or TP4 is associated with a CIR of 36.4 (15.5) and 42.9 (21.6), respectively, similar to that of patients with low or high positivity at any time-point. BCR/ABL1 MRD negativity (although based on small numbers) at TP1 or TP2 is reached less frequently compared with IG/TR MRD, but is associated with a similar very low risk of relapse (one relapse in 8 patients MRD negative at TP1), while patients with low or high positivity have instead a high risk of relapse, again similar to that observed for positive IG/TR MRD. The overall concordance between the two methods is 69%; for patients with positive MRD by both techniques, the estimated mean differences of BCR/ABL1 versus IG/TR results were significantly different from zero, and were consistent according to different TPs with significantly higher positivity by BCR/ABL1. There are also rare cases consistently negative by IG/TR and positive by BCR/ABL1 with a very favorable outcome.
Conclusion
MRD negativity by IG/TR is obtained more frequently than by BCR/ABL1 and it is highly predictive of a very favorable outcome and the earlier the negativity, the better the prognosis. Further investigations are needed to understand the biology in cases with discordant results, and in particular of those negative by IG/TR and positive by BCR/ABL1. The role of MRD in patients treated continuously with TKI inhibitors and without HSCT needs to be explored in current studies.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, BCR-ABL, Minimal residual disease (MRD), Pediatric
Abstract: LB2239
Type: Eposter Presentation
Background
Several studies showed that minimal residual disease (MRD) detection is a strong independent prognostic factor in childhood acute lymphoblastic leukemia (ALL) including Ph+ ALL treated with conventional chemotherapy. Very few data and of difficult interpretation are available on the predictive value of early MRD response in Ph+ ALL treated with tyrosine kinase inhibitors (TKI)s.
Aims
MRD was detected by real-time quantitative PCR of rearranged immunoglobulin/T-cell receptor (IG/TR) genes and/or BCR/ABL1 fusion transcript in the EsPhALL study to investigate its predictive value in patients treated with imatinib.
Methods
In the EsPhALL study, after induction therapy, patients received BFM high risk ALL therapy; imatinib was given intermittently during the intensive treatment phases for a total of 18 weeks or less, usually 10 weeks, if patients underwent hematopoietic stem cell transplantation (HSCT), indicated for large majority of patients. MRD on the bone marrow (BM) was monitored as an ancillary study after induction therapy (TP1), consolidation Phase IB (TP2), HR Block1 (TP3), HR Block2 (TP4), HR Block3, first and second reinduction, and at end of therapy. Quantitative PCR analysis was performed and interpreted according to Euro-MRD network guidelines for both IG/TR and BCR/ABL1.
Results
MRD negativity increases progressively, both by IG/TR (from 10% at TP1 to 57% at TP4) and by BCR/ABL1 (from 13% at TP1 to 30% at TP4). Conversely, the proportion of patients with highly positive MRD by IG/TR decreases from 78% at TP1 to 14% at TP4 and by BCR/ABL1, from 80% at TP1 to 57% only at TP4. The minority of patients IG/TR MRD negative at TP1 (N=9, 10%) had a very favorable outcome with no relapses, whereas patients with high or low MRD positivity had a similarly high 5-year cumulative incidence of relapse (CIR) (SE) of 35.2 (5.9) and 36.4 (15.4), respectively. Achieving MRD negativity at TP2 is also associated with low risk of relapse (5-year CIR (SE) 14.3 (9.8)), whereas achieving negativity only at TP3 or TP4 is associated with a CIR of 36.4 (15.5) and 42.9 (21.6), respectively, similar to that of patients with low or high positivity at any time-point. BCR/ABL1 MRD negativity (although based on small numbers) at TP1 or TP2 is reached less frequently compared with IG/TR MRD, but is associated with a similar very low risk of relapse (one relapse in 8 patients MRD negative at TP1), while patients with low or high positivity have instead a high risk of relapse, again similar to that observed for positive IG/TR MRD. The overall concordance between the two methods is 69%; for patients with positive MRD by both techniques, the estimated mean differences of BCR/ABL1 versus IG/TR results were significantly different from zero, and were consistent according to different TPs with significantly higher positivity by BCR/ABL1. There are also rare cases consistently negative by IG/TR and positive by BCR/ABL1 with a very favorable outcome.
Conclusion
MRD negativity by IG/TR is obtained more frequently than by BCR/ABL1 and it is highly predictive of a very favorable outcome and the earlier the negativity, the better the prognosis. Further investigations are needed to understand the biology in cases with discordant results, and in particular of those negative by IG/TR and positive by BCR/ABL1. The role of MRD in patients treated continuously with TKI inhibitors and without HSCT needs to be explored in current studies.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, BCR-ABL, Minimal residual disease (MRD), Pediatric
Type: Eposter Presentation
Background
Several studies showed that minimal residual disease (MRD) detection is a strong independent prognostic factor in childhood acute lymphoblastic leukemia (ALL) including Ph+ ALL treated with conventional chemotherapy. Very few data and of difficult interpretation are available on the predictive value of early MRD response in Ph+ ALL treated with tyrosine kinase inhibitors (TKI)s.
Aims
MRD was detected by real-time quantitative PCR of rearranged immunoglobulin/T-cell receptor (IG/TR) genes and/or BCR/ABL1 fusion transcript in the EsPhALL study to investigate its predictive value in patients treated with imatinib.
Methods
In the EsPhALL study, after induction therapy, patients received BFM high risk ALL therapy; imatinib was given intermittently during the intensive treatment phases for a total of 18 weeks or less, usually 10 weeks, if patients underwent hematopoietic stem cell transplantation (HSCT), indicated for large majority of patients. MRD on the bone marrow (BM) was monitored as an ancillary study after induction therapy (TP1), consolidation Phase IB (TP2), HR Block1 (TP3), HR Block2 (TP4), HR Block3, first and second reinduction, and at end of therapy. Quantitative PCR analysis was performed and interpreted according to Euro-MRD network guidelines for both IG/TR and BCR/ABL1.
Results
MRD negativity increases progressively, both by IG/TR (from 10% at TP1 to 57% at TP4) and by BCR/ABL1 (from 13% at TP1 to 30% at TP4). Conversely, the proportion of patients with highly positive MRD by IG/TR decreases from 78% at TP1 to 14% at TP4 and by BCR/ABL1, from 80% at TP1 to 57% only at TP4. The minority of patients IG/TR MRD negative at TP1 (N=9, 10%) had a very favorable outcome with no relapses, whereas patients with high or low MRD positivity had a similarly high 5-year cumulative incidence of relapse (CIR) (SE) of 35.2 (5.9) and 36.4 (15.4), respectively. Achieving MRD negativity at TP2 is also associated with low risk of relapse (5-year CIR (SE) 14.3 (9.8)), whereas achieving negativity only at TP3 or TP4 is associated with a CIR of 36.4 (15.5) and 42.9 (21.6), respectively, similar to that of patients with low or high positivity at any time-point. BCR/ABL1 MRD negativity (although based on small numbers) at TP1 or TP2 is reached less frequently compared with IG/TR MRD, but is associated with a similar very low risk of relapse (one relapse in 8 patients MRD negative at TP1), while patients with low or high positivity have instead a high risk of relapse, again similar to that observed for positive IG/TR MRD. The overall concordance between the two methods is 69%; for patients with positive MRD by both techniques, the estimated mean differences of BCR/ABL1 versus IG/TR results were significantly different from zero, and were consistent according to different TPs with significantly higher positivity by BCR/ABL1. There are also rare cases consistently negative by IG/TR and positive by BCR/ABL1 with a very favorable outcome.
Conclusion
MRD negativity by IG/TR is obtained more frequently than by BCR/ABL1 and it is highly predictive of a very favorable outcome and the earlier the negativity, the better the prognosis. Further investigations are needed to understand the biology in cases with discordant results, and in particular of those negative by IG/TR and positive by BCR/ABL1. The role of MRD in patients treated continuously with TKI inhibitors and without HSCT needs to be explored in current studies.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, BCR-ABL, Minimal residual disease (MRD), Pediatric
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