OUTCOMES OF OLDER PATIENTS EXPERIENCING REDUCED INTENSITY CONDITIONING ALLOGRAFT: RESULTS OF THE NCRI AML16 TRIAL
(Abstract release date: 05/21/15)
EHA Library. Russell N. 06/12/15; 103185; S126
Prof. Nigel Russell
Contributions
Contributions
Abstract
Abstract: S126
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 11:30 to 12.06.2015 11:45
Location: Room Lehar 1 + 2
Background
Reduced Intensity conditioning (RIC) is increasingly offered to older patients who are to undergo a stem cell transplant. We have previously shown that a RIC allograft, particularly from a sibling donor is beneficial in intermediate risk patients between the ages of 45-64, and may have advantages over myeloablative conditioning in patients aged 35-44. Based on this analysis of the UK NCRI AML15 trial in younger patients, the current recommendation within the NCRI AML trials is to transplant intermediate risk patients with a RIC allograft if a sibling is available excluding those who are NPM1+/ FLT3 wt.
Aims
We here present similar analyses from the UK NCRI AML16 trial extending this experience to older patients.
Methods
The UK NCRI AML16 trial ran from 2006-2012 and randomised patients, generally aged 60+, suitable for intensive chemotherapy between Daunorubicin/Ara-C (DA) and Daunorubicin/Clofarabine (DClo), both with or without Mylotarg, or between DA with or without etoposide and with or without ATRA. Patients could be randomised between 2 or 3 courses of therapy and maintenance or not with azacitidine. Because only 4/225 transplants took place in patients over the age of 70, attention was restricted to patients who were aged less than 70 years, achieved remission, and did not have core binding factor leukaemia. A total of 963 patients were studied, with transplant in first remission given to 162 patients (sibling allograft n=51, MUD n=93; other/unknown n=18). Follow-up is complete to 1st January 2014 with median follow-up for survival from CR of 46.3 months. Comparisons of confirmed allogeneic transplant in 1st remission versus not are carried out using Mantel-Byar analysis to allow for time to transplant, with patients censored at the time of non-RIC allo transplant.
Results
Among the 144 allografts, 93 had intermediate risk cytogenetics, 19 adverse risk, and 32 were unknown. In transplanted patients, survival from transplant was 36% at 5 years, and while the survival for sibling allografts (42%) was better than that for MUDs (37%) this did not reach statistical significance (p=0.2), and 84% of transplants in adverse risk cytogenetics were from an unrelated donor. In analyses adjusted for Wheatley risk group there was no significant difference in outcome (HR 1.27 (0.80-2.03) p=0.3). When comparing allograft versus no allograft, survival was significantly improved (35% vs 20%, HR 0.75 (0.61-0.93) p=0.006). When stratified by Wheatley risk group, there was no evidence of any interaction (p-value for trend 0.5), and the adjusted hazard ratio, allowing for differences in Wheatley group between transplant and no transplant was 0.76 (0.61-0.94), p=0.008 reflecting the consistent benefit. When considering type of transplant, sibling allograft performed consistently better than MUD in Mantel-Byar analyses across the risk groups (overall sibling 41%, MUD 35%, no SCT 20%; good risk 47% vs 42% vs 26%; standard risk 38% vs 34% vs 25%; poor risk, not reached vs 23% vs 8%).
Summary
The results are consistent with those seen in our analysis of AML15 While, particularly as patients get older, there will be selection for transplant on the basis of fitness, the analysis adjusted for clinical features of the disease shows that RIC transplant in first remission appears an attractive option for older patients with AML. While no significant difference was seen between sibling and MUD allograft, even after adjusting for Wheatley risk, outcomes are better in all Wheatley groups with sibling allografts.
Keyword(s): Acute myeloid leukemia, Reduced intensity transplantation
Session topic: Stem cell transplantation: Clinical 1
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 11:30 to 12.06.2015 11:45
Location: Room Lehar 1 + 2
Background
Reduced Intensity conditioning (RIC) is increasingly offered to older patients who are to undergo a stem cell transplant. We have previously shown that a RIC allograft, particularly from a sibling donor is beneficial in intermediate risk patients between the ages of 45-64, and may have advantages over myeloablative conditioning in patients aged 35-44. Based on this analysis of the UK NCRI AML15 trial in younger patients, the current recommendation within the NCRI AML trials is to transplant intermediate risk patients with a RIC allograft if a sibling is available excluding those who are NPM1+/ FLT3 wt.
Aims
We here present similar analyses from the UK NCRI AML16 trial extending this experience to older patients.
Methods
The UK NCRI AML16 trial ran from 2006-2012 and randomised patients, generally aged 60+, suitable for intensive chemotherapy between Daunorubicin/Ara-C (DA) and Daunorubicin/Clofarabine (DClo), both with or without Mylotarg, or between DA with or without etoposide and with or without ATRA. Patients could be randomised between 2 or 3 courses of therapy and maintenance or not with azacitidine. Because only 4/225 transplants took place in patients over the age of 70, attention was restricted to patients who were aged less than 70 years, achieved remission, and did not have core binding factor leukaemia. A total of 963 patients were studied, with transplant in first remission given to 162 patients (sibling allograft n=51, MUD n=93; other/unknown n=18). Follow-up is complete to 1st January 2014 with median follow-up for survival from CR of 46.3 months. Comparisons of confirmed allogeneic transplant in 1st remission versus not are carried out using Mantel-Byar analysis to allow for time to transplant, with patients censored at the time of non-RIC allo transplant.
Results
Among the 144 allografts, 93 had intermediate risk cytogenetics, 19 adverse risk, and 32 were unknown. In transplanted patients, survival from transplant was 36% at 5 years, and while the survival for sibling allografts (42%) was better than that for MUDs (37%) this did not reach statistical significance (p=0.2), and 84% of transplants in adverse risk cytogenetics were from an unrelated donor. In analyses adjusted for Wheatley risk group there was no significant difference in outcome (HR 1.27 (0.80-2.03) p=0.3). When comparing allograft versus no allograft, survival was significantly improved (35% vs 20%, HR 0.75 (0.61-0.93) p=0.006). When stratified by Wheatley risk group, there was no evidence of any interaction (p-value for trend 0.5), and the adjusted hazard ratio, allowing for differences in Wheatley group between transplant and no transplant was 0.76 (0.61-0.94), p=0.008 reflecting the consistent benefit. When considering type of transplant, sibling allograft performed consistently better than MUD in Mantel-Byar analyses across the risk groups (overall sibling 41%, MUD 35%, no SCT 20%; good risk 47% vs 42% vs 26%; standard risk 38% vs 34% vs 25%; poor risk, not reached vs 23% vs 8%).
Summary
The results are consistent with those seen in our analysis of AML15 While, particularly as patients get older, there will be selection for transplant on the basis of fitness, the analysis adjusted for clinical features of the disease shows that RIC transplant in first remission appears an attractive option for older patients with AML. While no significant difference was seen between sibling and MUD allograft, even after adjusting for Wheatley risk, outcomes are better in all Wheatley groups with sibling allografts.
Keyword(s): Acute myeloid leukemia, Reduced intensity transplantation
Session topic: Stem cell transplantation: Clinical 1
Abstract: S126
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 11:30 to 12.06.2015 11:45
Location: Room Lehar 1 + 2
Background
Reduced Intensity conditioning (RIC) is increasingly offered to older patients who are to undergo a stem cell transplant. We have previously shown that a RIC allograft, particularly from a sibling donor is beneficial in intermediate risk patients between the ages of 45-64, and may have advantages over myeloablative conditioning in patients aged 35-44. Based on this analysis of the UK NCRI AML15 trial in younger patients, the current recommendation within the NCRI AML trials is to transplant intermediate risk patients with a RIC allograft if a sibling is available excluding those who are NPM1+/ FLT3 wt.
Aims
We here present similar analyses from the UK NCRI AML16 trial extending this experience to older patients.
Methods
The UK NCRI AML16 trial ran from 2006-2012 and randomised patients, generally aged 60+, suitable for intensive chemotherapy between Daunorubicin/Ara-C (DA) and Daunorubicin/Clofarabine (DClo), both with or without Mylotarg, or between DA with or without etoposide and with or without ATRA. Patients could be randomised between 2 or 3 courses of therapy and maintenance or not with azacitidine. Because only 4/225 transplants took place in patients over the age of 70, attention was restricted to patients who were aged less than 70 years, achieved remission, and did not have core binding factor leukaemia. A total of 963 patients were studied, with transplant in first remission given to 162 patients (sibling allograft n=51, MUD n=93; other/unknown n=18). Follow-up is complete to 1st January 2014 with median follow-up for survival from CR of 46.3 months. Comparisons of confirmed allogeneic transplant in 1st remission versus not are carried out using Mantel-Byar analysis to allow for time to transplant, with patients censored at the time of non-RIC allo transplant.
Results
Among the 144 allografts, 93 had intermediate risk cytogenetics, 19 adverse risk, and 32 were unknown. In transplanted patients, survival from transplant was 36% at 5 years, and while the survival for sibling allografts (42%) was better than that for MUDs (37%) this did not reach statistical significance (p=0.2), and 84% of transplants in adverse risk cytogenetics were from an unrelated donor. In analyses adjusted for Wheatley risk group there was no significant difference in outcome (HR 1.27 (0.80-2.03) p=0.3). When comparing allograft versus no allograft, survival was significantly improved (35% vs 20%, HR 0.75 (0.61-0.93) p=0.006). When stratified by Wheatley risk group, there was no evidence of any interaction (p-value for trend 0.5), and the adjusted hazard ratio, allowing for differences in Wheatley group between transplant and no transplant was 0.76 (0.61-0.94), p=0.008 reflecting the consistent benefit. When considering type of transplant, sibling allograft performed consistently better than MUD in Mantel-Byar analyses across the risk groups (overall sibling 41%, MUD 35%, no SCT 20%; good risk 47% vs 42% vs 26%; standard risk 38% vs 34% vs 25%; poor risk, not reached vs 23% vs 8%).
Summary
The results are consistent with those seen in our analysis of AML15 While, particularly as patients get older, there will be selection for transplant on the basis of fitness, the analysis adjusted for clinical features of the disease shows that RIC transplant in first remission appears an attractive option for older patients with AML. While no significant difference was seen between sibling and MUD allograft, even after adjusting for Wheatley risk, outcomes are better in all Wheatley groups with sibling allografts.
Keyword(s): Acute myeloid leukemia, Reduced intensity transplantation
Session topic: Stem cell transplantation: Clinical 1
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 11:30 to 12.06.2015 11:45
Location: Room Lehar 1 + 2
Background
Reduced Intensity conditioning (RIC) is increasingly offered to older patients who are to undergo a stem cell transplant. We have previously shown that a RIC allograft, particularly from a sibling donor is beneficial in intermediate risk patients between the ages of 45-64, and may have advantages over myeloablative conditioning in patients aged 35-44. Based on this analysis of the UK NCRI AML15 trial in younger patients, the current recommendation within the NCRI AML trials is to transplant intermediate risk patients with a RIC allograft if a sibling is available excluding those who are NPM1+/ FLT3 wt.
Aims
We here present similar analyses from the UK NCRI AML16 trial extending this experience to older patients.
Methods
The UK NCRI AML16 trial ran from 2006-2012 and randomised patients, generally aged 60+, suitable for intensive chemotherapy between Daunorubicin/Ara-C (DA) and Daunorubicin/Clofarabine (DClo), both with or without Mylotarg, or between DA with or without etoposide and with or without ATRA. Patients could be randomised between 2 or 3 courses of therapy and maintenance or not with azacitidine. Because only 4/225 transplants took place in patients over the age of 70, attention was restricted to patients who were aged less than 70 years, achieved remission, and did not have core binding factor leukaemia. A total of 963 patients were studied, with transplant in first remission given to 162 patients (sibling allograft n=51, MUD n=93; other/unknown n=18). Follow-up is complete to 1st January 2014 with median follow-up for survival from CR of 46.3 months. Comparisons of confirmed allogeneic transplant in 1st remission versus not are carried out using Mantel-Byar analysis to allow for time to transplant, with patients censored at the time of non-RIC allo transplant.
Results
Among the 144 allografts, 93 had intermediate risk cytogenetics, 19 adverse risk, and 32 were unknown. In transplanted patients, survival from transplant was 36% at 5 years, and while the survival for sibling allografts (42%) was better than that for MUDs (37%) this did not reach statistical significance (p=0.2), and 84% of transplants in adverse risk cytogenetics were from an unrelated donor. In analyses adjusted for Wheatley risk group there was no significant difference in outcome (HR 1.27 (0.80-2.03) p=0.3). When comparing allograft versus no allograft, survival was significantly improved (35% vs 20%, HR 0.75 (0.61-0.93) p=0.006). When stratified by Wheatley risk group, there was no evidence of any interaction (p-value for trend 0.5), and the adjusted hazard ratio, allowing for differences in Wheatley group between transplant and no transplant was 0.76 (0.61-0.94), p=0.008 reflecting the consistent benefit. When considering type of transplant, sibling allograft performed consistently better than MUD in Mantel-Byar analyses across the risk groups (overall sibling 41%, MUD 35%, no SCT 20%; good risk 47% vs 42% vs 26%; standard risk 38% vs 34% vs 25%; poor risk, not reached vs 23% vs 8%).
Summary
The results are consistent with those seen in our analysis of AML15 While, particularly as patients get older, there will be selection for transplant on the basis of fitness, the analysis adjusted for clinical features of the disease shows that RIC transplant in first remission appears an attractive option for older patients with AML. While no significant difference was seen between sibling and MUD allograft, even after adjusting for Wheatley risk, outcomes are better in all Wheatley groups with sibling allografts.
Keyword(s): Acute myeloid leukemia, Reduced intensity transplantation
Session topic: Stem cell transplantation: Clinical 1
{{ help_message }}
{{filter}}