DE-ESCALATION OF INTENSITY DID NOT AFFECT THE LONG-TERM OUTCOME NEITHER IN T-ALL NOR IN BCP-ALL IF NON-INTERRUPTIVE TREATMENT IS APPLIED: RESULTS OF THE RUSSIAN ALL STUDY GROUP.
(Abstract release date: 05/19/16)
EHA Library. Parovichnikova E. 06/09/16; 132404; E855
Dr. Elena Parovichnikova
Contributions
Contributions
Abstract
Abstract: E855
Type: Eposter Presentation
Background
More aggressive pediatric-like protocols and high portion of allogeneic HSCT are now a standard approach to treatment in adult acute lymphoblastic leukemia (ALL). Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the different approach: de-escalated but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933.
Aims
To assess non-intensive and non-interruptive approach to ALL treatment.
Methods
The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks Pdn/Dexa with 3 instead of 4 Dauno/Vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks –continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications– with 1 day HD MTX (1,5 g/m2)and with 1 d HD ARA-C (2 g/m2), both with L-asp and 3 d dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. For T-ALL patients auto-HSCT after non-myeloablative BEAM conditioning followed by the protocol maintenance was an option as late consolidation. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11), L>100). No central MRD monitoring was performed. Since Apr 2009 till Feb 2016, 298 Ph-negative ALL pts with a median age 28 years (15-55), f/m 137/161 were recruited. In 6 pts phenotype was unknown, B-lineage ALL was diagnosed in - 62,4% (n=182), T-lineage ALL – 36,6% (n=107), biphenotypic - 1% (n=3). In BCP-ALL 31 patients (n=17%) were not qualified by the risk in the data-base; 72,8% (n=110) were in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive). In T-ALL 7 patients (n=8%) were not qualified by the risk in the data-base; 76% (n=76) were in the high risk (HR) group (WBC >100; EGIL TI/II,TIV, LDH > 2N; late CR). The analysis was performed in february 2016.
Results
CR rate in 284 available for analysis pts was 86,7% (n=246), induction death occurred in 9,1% (n=26), resistance was registered in 4,2% (n=12). Late responders constituted 13,1% (n=20) in BCP-ALL and 28,9% (n=24) in T-ALL. In 89 CR T-ALL pts 35 auto-HSCT were performed at a median of 5,8 mo of CR. Allogeneic BMT was performed only in 18 of 256 patients who survived induction (7,0%). Totally 49 pts (19,9%) had relapsed. At 60 mo OS for the whole cohort constituted – 58,9% (BCP-ALL -53,3%, T-ALL-67,5%), DFS – 64.9% (BCP-ALL – 56,2%, T-ALL – 79,5%), relapse probability (RP) – 25% (BCP-ALL -30,6%, T-ALL-15,8%). In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d) age (>30 y) for BCP-ALL became statistically significant for OS and RP, WBC for DFS and RP, risk group for DFS, LDH for RP, t(4;11) for OS, DFS and RP. In T-ALL in a univariate analysis only LDH was significant for OS. In a multivariate analysis no common risk factors were significant non in T-ALL, nor in BCP-ALL.
Conclusion
Our data demonstrate that the de-escalation of intensity but constant non-interruptive treatment is rather effective in adult ALL producing more than 50% OS in BCP-ALL and 65% in T-ALL. We believe that this approach, without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that the compliance of the pts to the protocol should be very strict.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Autologous bone marrow transplant, Chemotherapy
Type: Eposter Presentation
Background
More aggressive pediatric-like protocols and high portion of allogeneic HSCT are now a standard approach to treatment in adult acute lymphoblastic leukemia (ALL). Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the different approach: de-escalated but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933.
Aims
To assess non-intensive and non-interruptive approach to ALL treatment.
Methods
The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks Pdn/Dexa with 3 instead of 4 Dauno/Vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks –continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications– with 1 day HD MTX (1,5 g/m2)and with 1 d HD ARA-C (2 g/m2), both with L-asp and 3 d dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. For T-ALL patients auto-HSCT after non-myeloablative BEAM conditioning followed by the protocol maintenance was an option as late consolidation. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11), L>100). No central MRD monitoring was performed. Since Apr 2009 till Feb 2016, 298 Ph-negative ALL pts with a median age 28 years (15-55), f/m 137/161 were recruited. In 6 pts phenotype was unknown, B-lineage ALL was diagnosed in - 62,4% (n=182), T-lineage ALL – 36,6% (n=107), biphenotypic - 1% (n=3). In BCP-ALL 31 patients (n=17%) were not qualified by the risk in the data-base; 72,8% (n=110) were in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive). In T-ALL 7 patients (n=8%) were not qualified by the risk in the data-base; 76% (n=76) were in the high risk (HR) group (WBC >100; EGIL TI/II,TIV, LDH > 2N; late CR). The analysis was performed in february 2016.
Results
CR rate in 284 available for analysis pts was 86,7% (n=246), induction death occurred in 9,1% (n=26), resistance was registered in 4,2% (n=12). Late responders constituted 13,1% (n=20) in BCP-ALL and 28,9% (n=24) in T-ALL. In 89 CR T-ALL pts 35 auto-HSCT were performed at a median of 5,8 mo of CR. Allogeneic BMT was performed only in 18 of 256 patients who survived induction (7,0%). Totally 49 pts (19,9%) had relapsed. At 60 mo OS for the whole cohort constituted – 58,9% (BCP-ALL -53,3%, T-ALL-67,5%), DFS – 64.9% (BCP-ALL – 56,2%, T-ALL – 79,5%), relapse probability (RP) – 25% (BCP-ALL -30,6%, T-ALL-15,8%). In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d) age (>30 y) for BCP-ALL became statistically significant for OS and RP, WBC for DFS and RP, risk group for DFS, LDH for RP, t(4;11) for OS, DFS and RP. In T-ALL in a univariate analysis only LDH was significant for OS. In a multivariate analysis no common risk factors were significant non in T-ALL, nor in BCP-ALL.
Conclusion
Our data demonstrate that the de-escalation of intensity but constant non-interruptive treatment is rather effective in adult ALL producing more than 50% OS in BCP-ALL and 65% in T-ALL. We believe that this approach, without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that the compliance of the pts to the protocol should be very strict.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Autologous bone marrow transplant, Chemotherapy
Abstract: E855
Type: Eposter Presentation
Background
More aggressive pediatric-like protocols and high portion of allogeneic HSCT are now a standard approach to treatment in adult acute lymphoblastic leukemia (ALL). Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the different approach: de-escalated but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933.
Aims
To assess non-intensive and non-interruptive approach to ALL treatment.
Methods
The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks Pdn/Dexa with 3 instead of 4 Dauno/Vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks –continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications– with 1 day HD MTX (1,5 g/m2)and with 1 d HD ARA-C (2 g/m2), both with L-asp and 3 d dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. For T-ALL patients auto-HSCT after non-myeloablative BEAM conditioning followed by the protocol maintenance was an option as late consolidation. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11), L>100). No central MRD monitoring was performed. Since Apr 2009 till Feb 2016, 298 Ph-negative ALL pts with a median age 28 years (15-55), f/m 137/161 were recruited. In 6 pts phenotype was unknown, B-lineage ALL was diagnosed in - 62,4% (n=182), T-lineage ALL – 36,6% (n=107), biphenotypic - 1% (n=3). In BCP-ALL 31 patients (n=17%) were not qualified by the risk in the data-base; 72,8% (n=110) were in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive). In T-ALL 7 patients (n=8%) were not qualified by the risk in the data-base; 76% (n=76) were in the high risk (HR) group (WBC >100; EGIL TI/II,TIV, LDH > 2N; late CR). The analysis was performed in february 2016.
Results
CR rate in 284 available for analysis pts was 86,7% (n=246), induction death occurred in 9,1% (n=26), resistance was registered in 4,2% (n=12). Late responders constituted 13,1% (n=20) in BCP-ALL and 28,9% (n=24) in T-ALL. In 89 CR T-ALL pts 35 auto-HSCT were performed at a median of 5,8 mo of CR. Allogeneic BMT was performed only in 18 of 256 patients who survived induction (7,0%). Totally 49 pts (19,9%) had relapsed. At 60 mo OS for the whole cohort constituted – 58,9% (BCP-ALL -53,3%, T-ALL-67,5%), DFS – 64.9% (BCP-ALL – 56,2%, T-ALL – 79,5%), relapse probability (RP) – 25% (BCP-ALL -30,6%, T-ALL-15,8%). In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d) age (>30 y) for BCP-ALL became statistically significant for OS and RP, WBC for DFS and RP, risk group for DFS, LDH for RP, t(4;11) for OS, DFS and RP. In T-ALL in a univariate analysis only LDH was significant for OS. In a multivariate analysis no common risk factors were significant non in T-ALL, nor in BCP-ALL.
Conclusion
Our data demonstrate that the de-escalation of intensity but constant non-interruptive treatment is rather effective in adult ALL producing more than 50% OS in BCP-ALL and 65% in T-ALL. We believe that this approach, without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that the compliance of the pts to the protocol should be very strict.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Autologous bone marrow transplant, Chemotherapy
Type: Eposter Presentation
Background
More aggressive pediatric-like protocols and high portion of allogeneic HSCT are now a standard approach to treatment in adult acute lymphoblastic leukemia (ALL). Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the different approach: de-escalated but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933.
Aims
To assess non-intensive and non-interruptive approach to ALL treatment.
Methods
The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks Pdn/Dexa with 3 instead of 4 Dauno/Vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks –continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications– with 1 day HD MTX (1,5 g/m2)and with 1 d HD ARA-C (2 g/m2), both with L-asp and 3 d dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. For T-ALL patients auto-HSCT after non-myeloablative BEAM conditioning followed by the protocol maintenance was an option as late consolidation. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11), L>100). No central MRD monitoring was performed. Since Apr 2009 till Feb 2016, 298 Ph-negative ALL pts with a median age 28 years (15-55), f/m 137/161 were recruited. In 6 pts phenotype was unknown, B-lineage ALL was diagnosed in - 62,4% (n=182), T-lineage ALL – 36,6% (n=107), biphenotypic - 1% (n=3). In BCP-ALL 31 patients (n=17%) were not qualified by the risk in the data-base; 72,8% (n=110) were in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive). In T-ALL 7 patients (n=8%) were not qualified by the risk in the data-base; 76% (n=76) were in the high risk (HR) group (WBC >100; EGIL TI/II,TIV, LDH > 2N; late CR). The analysis was performed in february 2016.
Results
CR rate in 284 available for analysis pts was 86,7% (n=246), induction death occurred in 9,1% (n=26), resistance was registered in 4,2% (n=12). Late responders constituted 13,1% (n=20) in BCP-ALL and 28,9% (n=24) in T-ALL. In 89 CR T-ALL pts 35 auto-HSCT were performed at a median of 5,8 mo of CR. Allogeneic BMT was performed only in 18 of 256 patients who survived induction (7,0%). Totally 49 pts (19,9%) had relapsed. At 60 mo OS for the whole cohort constituted – 58,9% (BCP-ALL -53,3%, T-ALL-67,5%), DFS – 64.9% (BCP-ALL – 56,2%, T-ALL – 79,5%), relapse probability (RP) – 25% (BCP-ALL -30,6%, T-ALL-15,8%). In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d) age (>30 y) for BCP-ALL became statistically significant for OS and RP, WBC for DFS and RP, risk group for DFS, LDH for RP, t(4;11) for OS, DFS and RP. In T-ALL in a univariate analysis only LDH was significant for OS. In a multivariate analysis no common risk factors were significant non in T-ALL, nor in BCP-ALL.
Conclusion
Our data demonstrate that the de-escalation of intensity but constant non-interruptive treatment is rather effective in adult ALL producing more than 50% OS in BCP-ALL and 65% in T-ALL. We believe that this approach, without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that the compliance of the pts to the protocol should be very strict.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Autologous bone marrow transplant, Chemotherapy
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