IMPROVED SURVIVAL IN PEDIATRIC ACUTE MYELOID LEUKEMIA: A REPORT FROM AML-BFM TRIALS 1987-2011.
(Abstract release date: 05/19/16)
EHA Library. Rasche M. 06/11/16; 135238; S482
Dr. Mareike Rasche
Contributions
Contributions
Abstract
Abstract: S482
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A2
Background
Prognosis of children with acute myeloid leukemia (AML) improved within the recent decades. Study groups worldwide performed prospective randomized trials to select more effective and/or less toxic drugs. Several approaches such very high dosages of cytarabine versus high cumulative dosages of anthracyclins or performance of allogeneic stem cell transplantation (HSCT) versus chemotherapy only led to rather similar results in terms of event-free (EFS) and overall survival (OS).
Aims
Therefore we asked if the improvement of survival is dependent from particular therapy elements identified in randomized trials or rather a correlation with time. This would implicate that factors such as intensity, supportive care or risk group stratification have a much higher impact than the selection of a specific drug.
Methods
In total, 1873 children (0 to 18 yrs) enrolled to the AML-BFM trials from 1987 until 2011 were included (excluding Down’s Syndrome and acute promyeloblastic leukemia). The AML-BFM Study group recruited on population-based trials all children with AML from Germany and since 1998 from Czech Republic, Austria and Switzerland. Outcome data were analyzed not only per trial but per 2- and 3-year-periods respectively (Kaplan-Meier).
Results
The 5–year EFS and OS (1987 to 2011) increased from 41±3% to 51±2% and 49±3% to 72±2%, respectively. The table shows EFS and OS of 3 year periods. The comparison to the AML-BFM trial episodes indicate that a stepwise increase in long-term survival was achieved –according to protocols- by more intensive chemotherapy from 1987-1997. Analysis of 2 and 3-yr-periods shows changes within these study protocols dependent on particular therapy elements and amendments (Figure 1). After 1998 the following years rather show a continuous improvement but only in OS. An increasing gap between EFS and OS (period 1987-1989: 9%; 2008-2010: 24%) was observed. A relevant and unexpected increase in OS was observed in 2001/02. At this time point there was no change in first line protocol, but in addition an international relapse protocol was implemented. The survival after relapse increased from 17±3 up to 44±3%.
Conclusion
Since 1987, several changes influenced AML therapy. The intensity of treatment increased until the AML-BFM 98 trial, in supportive care mainly the general introduction of antimycotics (recommendation 1993) might be the most relevant change. Since 1995 OS improved continuously until 2008, whereas EFS did not change significantly. Although, the slightly reduced relapse rate might suggest that 2nd line treatment becomes more difficult due to the selection of the more resistant AML, from the data it is clear that the efficacy of 2nd line therapy improved.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Pediatric
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A2
Background
Prognosis of children with acute myeloid leukemia (AML) improved within the recent decades. Study groups worldwide performed prospective randomized trials to select more effective and/or less toxic drugs. Several approaches such very high dosages of cytarabine versus high cumulative dosages of anthracyclins or performance of allogeneic stem cell transplantation (HSCT) versus chemotherapy only led to rather similar results in terms of event-free (EFS) and overall survival (OS).
Aims
Therefore we asked if the improvement of survival is dependent from particular therapy elements identified in randomized trials or rather a correlation with time. This would implicate that factors such as intensity, supportive care or risk group stratification have a much higher impact than the selection of a specific drug.
Methods
In total, 1873 children (0 to 18 yrs) enrolled to the AML-BFM trials from 1987 until 2011 were included (excluding Down’s Syndrome and acute promyeloblastic leukemia). The AML-BFM Study group recruited on population-based trials all children with AML from Germany and since 1998 from Czech Republic, Austria and Switzerland. Outcome data were analyzed not only per trial but per 2- and 3-year-periods respectively (Kaplan-Meier).
Results
The 5–year EFS and OS (1987 to 2011) increased from 41±3% to 51±2% and 49±3% to 72±2%, respectively. The table shows EFS and OS of 3 year periods. The comparison to the AML-BFM trial episodes indicate that a stepwise increase in long-term survival was achieved –according to protocols- by more intensive chemotherapy from 1987-1997. Analysis of 2 and 3-yr-periods shows changes within these study protocols dependent on particular therapy elements and amendments (Figure 1). After 1998 the following years rather show a continuous improvement but only in OS. An increasing gap between EFS and OS (period 1987-1989: 9%; 2008-2010: 24%) was observed. A relevant and unexpected increase in OS was observed in 2001/02. At this time point there was no change in first line protocol, but in addition an international relapse protocol was implemented. The survival after relapse increased from 17±3 up to 44±3%.
| 3-yr-period | [n] | EFS ±SE [%] | OS ±SE [%] | |
| 1987-1989 | 134 | 43±4% | 52±4% | |
| 1990-1992 | 161 | 39±4% | 47±3% | |
| 1993-1995 | 249 | 52±3% | 58±3% | |
| 1996-1998 | 284 | 48±3% | 58±3% | |
| 1999-2001 | 250 | 50±3% | 64±3% | |
| 2002-2004 | 246 | 51±3% | 65±3% | |
| 2005-2007 | 245 | 52±3% | 74±4% | |
| 2008-2010 | 232 | 46±4% | 70±3% | |
| AML-BFM 87 (1987-1992) | 295 | 41±3% | 49±3% | |
| AML-BFM 93 (1993-1997) | 488 | 50±2% | 57±2% | |
| AML-BFM 98 (1998-2003) | 465 | 49±2% | 63±2% | |
| AML-BFM 2004 (2004-2011) | 625 | 51±2% | 72±2% |
Conclusion
Since 1987, several changes influenced AML therapy. The intensity of treatment increased until the AML-BFM 98 trial, in supportive care mainly the general introduction of antimycotics (recommendation 1993) might be the most relevant change. Since 1995 OS improved continuously until 2008, whereas EFS did not change significantly. Although, the slightly reduced relapse rate might suggest that 2nd line treatment becomes more difficult due to the selection of the more resistant AML, from the data it is clear that the efficacy of 2nd line therapy improved.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Pediatric
Abstract: S482
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A2
Background
Prognosis of children with acute myeloid leukemia (AML) improved within the recent decades. Study groups worldwide performed prospective randomized trials to select more effective and/or less toxic drugs. Several approaches such very high dosages of cytarabine versus high cumulative dosages of anthracyclins or performance of allogeneic stem cell transplantation (HSCT) versus chemotherapy only led to rather similar results in terms of event-free (EFS) and overall survival (OS).
Aims
Therefore we asked if the improvement of survival is dependent from particular therapy elements identified in randomized trials or rather a correlation with time. This would implicate that factors such as intensity, supportive care or risk group stratification have a much higher impact than the selection of a specific drug.
Methods
In total, 1873 children (0 to 18 yrs) enrolled to the AML-BFM trials from 1987 until 2011 were included (excluding Down’s Syndrome and acute promyeloblastic leukemia). The AML-BFM Study group recruited on population-based trials all children with AML from Germany and since 1998 from Czech Republic, Austria and Switzerland. Outcome data were analyzed not only per trial but per 2- and 3-year-periods respectively (Kaplan-Meier).
Results
The 5–year EFS and OS (1987 to 2011) increased from 41±3% to 51±2% and 49±3% to 72±2%, respectively. The table shows EFS and OS of 3 year periods. The comparison to the AML-BFM trial episodes indicate that a stepwise increase in long-term survival was achieved –according to protocols- by more intensive chemotherapy from 1987-1997. Analysis of 2 and 3-yr-periods shows changes within these study protocols dependent on particular therapy elements and amendments (Figure 1). After 1998 the following years rather show a continuous improvement but only in OS. An increasing gap between EFS and OS (period 1987-1989: 9%; 2008-2010: 24%) was observed. A relevant and unexpected increase in OS was observed in 2001/02. At this time point there was no change in first line protocol, but in addition an international relapse protocol was implemented. The survival after relapse increased from 17±3 up to 44±3%.
Conclusion
Since 1987, several changes influenced AML therapy. The intensity of treatment increased until the AML-BFM 98 trial, in supportive care mainly the general introduction of antimycotics (recommendation 1993) might be the most relevant change. Since 1995 OS improved continuously until 2008, whereas EFS did not change significantly. Although, the slightly reduced relapse rate might suggest that 2nd line treatment becomes more difficult due to the selection of the more resistant AML, from the data it is clear that the efficacy of 2nd line therapy improved.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Pediatric
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A2
Background
Prognosis of children with acute myeloid leukemia (AML) improved within the recent decades. Study groups worldwide performed prospective randomized trials to select more effective and/or less toxic drugs. Several approaches such very high dosages of cytarabine versus high cumulative dosages of anthracyclins or performance of allogeneic stem cell transplantation (HSCT) versus chemotherapy only led to rather similar results in terms of event-free (EFS) and overall survival (OS).
Aims
Therefore we asked if the improvement of survival is dependent from particular therapy elements identified in randomized trials or rather a correlation with time. This would implicate that factors such as intensity, supportive care or risk group stratification have a much higher impact than the selection of a specific drug.
Methods
In total, 1873 children (0 to 18 yrs) enrolled to the AML-BFM trials from 1987 until 2011 were included (excluding Down’s Syndrome and acute promyeloblastic leukemia). The AML-BFM Study group recruited on population-based trials all children with AML from Germany and since 1998 from Czech Republic, Austria and Switzerland. Outcome data were analyzed not only per trial but per 2- and 3-year-periods respectively (Kaplan-Meier).
Results
The 5–year EFS and OS (1987 to 2011) increased from 41±3% to 51±2% and 49±3% to 72±2%, respectively. The table shows EFS and OS of 3 year periods. The comparison to the AML-BFM trial episodes indicate that a stepwise increase in long-term survival was achieved –according to protocols- by more intensive chemotherapy from 1987-1997. Analysis of 2 and 3-yr-periods shows changes within these study protocols dependent on particular therapy elements and amendments (Figure 1). After 1998 the following years rather show a continuous improvement but only in OS. An increasing gap between EFS and OS (period 1987-1989: 9%; 2008-2010: 24%) was observed. A relevant and unexpected increase in OS was observed in 2001/02. At this time point there was no change in first line protocol, but in addition an international relapse protocol was implemented. The survival after relapse increased from 17±3 up to 44±3%.
| 3-yr-period | [n] | EFS ±SE [%] | OS ±SE [%] | |
| 1987-1989 | 134 | 43±4% | 52±4% | |
| 1990-1992 | 161 | 39±4% | 47±3% | |
| 1993-1995 | 249 | 52±3% | 58±3% | |
| 1996-1998 | 284 | 48±3% | 58±3% | |
| 1999-2001 | 250 | 50±3% | 64±3% | |
| 2002-2004 | 246 | 51±3% | 65±3% | |
| 2005-2007 | 245 | 52±3% | 74±4% | |
| 2008-2010 | 232 | 46±4% | 70±3% | |
| AML-BFM 87 (1987-1992) | 295 | 41±3% | 49±3% | |
| AML-BFM 93 (1993-1997) | 488 | 50±2% | 57±2% | |
| AML-BFM 98 (1998-2003) | 465 | 49±2% | 63±2% | |
| AML-BFM 2004 (2004-2011) | 625 | 51±2% | 72±2% |
Conclusion
Since 1987, several changes influenced AML therapy. The intensity of treatment increased until the AML-BFM 98 trial, in supportive care mainly the general introduction of antimycotics (recommendation 1993) might be the most relevant change. Since 1995 OS improved continuously until 2008, whereas EFS did not change significantly. Although, the slightly reduced relapse rate might suggest that 2nd line treatment becomes more difficult due to the selection of the more resistant AML, from the data it is clear that the efficacy of 2nd line therapy improved.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Pediatric
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