DECREASING EARLY DEATHS IN ACUTE PROMYELOCYTIC LEUKEMIA (APL) IN AN ACADEMIC CENTER IN THE US BY USING A SIMPLIFIED TREATMENT ALGORITHM AND DEDICATED APL EXPERTS.
(Abstract release date: 05/19/16)
EHA Library. Jillella A. 06/09/16; 134553; PB1653
Dr. Anand Jillella
Contributions
Contributions
Abstract
Abstract: PB1653
Type: Publication Only
Background
APL is a highly curable malignancy with reported survival above 90% in many large co-operative group studies. Treatment of low and intermediate risk patients showed an expected survival of 99% with retinoic acid (ATRA)/Arsenic (ATO) combination versus 91 % with ATRA/chemotherapy at 2 years. These spectacular results are not evident in the general population. US SEER data showed that 1 and 5 year relative survival in APL patients is 71% and 65%. Studies from Swedish Cancer Registry and Brazil showed that early deaths (ED) can be approximately 30%. This is in contrast to observation in clinical trials where the early mortality is approximately 5%. Common causes of death are hemorrhagic complications (HC), differentiation syndrome (DS), infection and multi-organ failure (MOF). It is now agreed that the most common cause of treatment failure in APL is ED; and decreasing ED will improve population wide survival in this most curable leukemia. We report our institutional experience that showed a decrease in ED by using a streamlined set of guidelines and expert advice as needed.
Aims
To identify the impact of streamlined guidelines
Methods
We reviewed charts of patients with newly diagnosed APL and treated at our institution between January 2007 and August 2013 (earlier group). We compared these outcomes with those diagnosed from September 2013 to January 2016 (newer group) when we put in place a set of streamlined guidelines to improve ED. In addition to the guidelines, three faculty members with an interest in APL provided input as needed in the management of all newly diagnosed patients.
Results
From 01/2007 to 01/2016, 108 patients were treated; 75 patients managed prior to and 33 after establishment of guidelines. One Jehovah’s Wittness patient was excluded from the newer group for refusing transfusions and subsequently died. Median age was similar at 45 years in both groups (range 19-86 and 21-81 respectively). Patients above 60 years were approximately 30% (23/75 and 10/32) and platelet count (29 and 30) were similar in both groups. In the earlier group, median white cell count (WBC) (4.2 and 2.2) and proportion of high risk (WBC >10,000/ml) patients (36% vs 21%) were higher. In the earlier group, induction regimen consisted of ATRA in combination with anthracycline (50, 66%), arsenic (12, 16%), other chemotherapy (8, 10%) or single agent ATRA in (5, 6%) patients. In contrast in the newer group, ATRA with ATO was the preferred induction regimen in 24 (75%) and anthracycline based treatment was used in 6 (18%) patients. 2 patients received ATRA alone.Overall the ED rate was higher in the earlier group with 19 patients (25%) dying in the first month. The causes of death were DIC (9), DS (7) and infection/MOF (3). 5 patients presented with large intracranial bleeds and were extremely ill. Excluding the patients that were referred late, the mortality was 18%; similar to some single institution studies but more than what is seen in clinical trials.After the institution of our algorithm, mortality was reduced to 9.4% (3/32 ED). Cause of ED was DS (2) and DIC (1). The incidence of severe DS (18% vs 6%) and sepsis (28% vs 16%) were lower in the newer group. The improved outcomes (25% vs 9.3%) is probably multifactorial due to lower number of high risk patients, more frequent arsenic based induction, use of streamlined guidelines and advice by dedicated APL experts.
Conclusion
Our experience shows that a streamlined treatment algorithm along with input from experts will result in better outcomes in this most curable hematological malignancy even at academic centers. We believe our experience warrants large scale implementation of our model and is presently approved as an ECOG/ACRIN trial.
Session topic: E-poster
Keyword(s): APL, Induction
Type: Publication Only
Background
APL is a highly curable malignancy with reported survival above 90% in many large co-operative group studies. Treatment of low and intermediate risk patients showed an expected survival of 99% with retinoic acid (ATRA)/Arsenic (ATO) combination versus 91 % with ATRA/chemotherapy at 2 years. These spectacular results are not evident in the general population. US SEER data showed that 1 and 5 year relative survival in APL patients is 71% and 65%. Studies from Swedish Cancer Registry and Brazil showed that early deaths (ED) can be approximately 30%. This is in contrast to observation in clinical trials where the early mortality is approximately 5%. Common causes of death are hemorrhagic complications (HC), differentiation syndrome (DS), infection and multi-organ failure (MOF). It is now agreed that the most common cause of treatment failure in APL is ED; and decreasing ED will improve population wide survival in this most curable leukemia. We report our institutional experience that showed a decrease in ED by using a streamlined set of guidelines and expert advice as needed.
Aims
To identify the impact of streamlined guidelines
Methods
We reviewed charts of patients with newly diagnosed APL and treated at our institution between January 2007 and August 2013 (earlier group). We compared these outcomes with those diagnosed from September 2013 to January 2016 (newer group) when we put in place a set of streamlined guidelines to improve ED. In addition to the guidelines, three faculty members with an interest in APL provided input as needed in the management of all newly diagnosed patients.
Results
From 01/2007 to 01/2016, 108 patients were treated; 75 patients managed prior to and 33 after establishment of guidelines. One Jehovah’s Wittness patient was excluded from the newer group for refusing transfusions and subsequently died. Median age was similar at 45 years in both groups (range 19-86 and 21-81 respectively). Patients above 60 years were approximately 30% (23/75 and 10/32) and platelet count (29 and 30) were similar in both groups. In the earlier group, median white cell count (WBC) (4.2 and 2.2) and proportion of high risk (WBC >10,000/ml) patients (36% vs 21%) were higher. In the earlier group, induction regimen consisted of ATRA in combination with anthracycline (50, 66%), arsenic (12, 16%), other chemotherapy (8, 10%) or single agent ATRA in (5, 6%) patients. In contrast in the newer group, ATRA with ATO was the preferred induction regimen in 24 (75%) and anthracycline based treatment was used in 6 (18%) patients. 2 patients received ATRA alone.Overall the ED rate was higher in the earlier group with 19 patients (25%) dying in the first month. The causes of death were DIC (9), DS (7) and infection/MOF (3). 5 patients presented with large intracranial bleeds and were extremely ill. Excluding the patients that were referred late, the mortality was 18%; similar to some single institution studies but more than what is seen in clinical trials.After the institution of our algorithm, mortality was reduced to 9.4% (3/32 ED). Cause of ED was DS (2) and DIC (1). The incidence of severe DS (18% vs 6%) and sepsis (28% vs 16%) were lower in the newer group. The improved outcomes (25% vs 9.3%) is probably multifactorial due to lower number of high risk patients, more frequent arsenic based induction, use of streamlined guidelines and advice by dedicated APL experts.
Conclusion
Our experience shows that a streamlined treatment algorithm along with input from experts will result in better outcomes in this most curable hematological malignancy even at academic centers. We believe our experience warrants large scale implementation of our model and is presently approved as an ECOG/ACRIN trial.
Session topic: E-poster
Keyword(s): APL, Induction
Abstract: PB1653
Type: Publication Only
Background
APL is a highly curable malignancy with reported survival above 90% in many large co-operative group studies. Treatment of low and intermediate risk patients showed an expected survival of 99% with retinoic acid (ATRA)/Arsenic (ATO) combination versus 91 % with ATRA/chemotherapy at 2 years. These spectacular results are not evident in the general population. US SEER data showed that 1 and 5 year relative survival in APL patients is 71% and 65%. Studies from Swedish Cancer Registry and Brazil showed that early deaths (ED) can be approximately 30%. This is in contrast to observation in clinical trials where the early mortality is approximately 5%. Common causes of death are hemorrhagic complications (HC), differentiation syndrome (DS), infection and multi-organ failure (MOF). It is now agreed that the most common cause of treatment failure in APL is ED; and decreasing ED will improve population wide survival in this most curable leukemia. We report our institutional experience that showed a decrease in ED by using a streamlined set of guidelines and expert advice as needed.
Aims
To identify the impact of streamlined guidelines
Methods
We reviewed charts of patients with newly diagnosed APL and treated at our institution between January 2007 and August 2013 (earlier group). We compared these outcomes with those diagnosed from September 2013 to January 2016 (newer group) when we put in place a set of streamlined guidelines to improve ED. In addition to the guidelines, three faculty members with an interest in APL provided input as needed in the management of all newly diagnosed patients.
Results
From 01/2007 to 01/2016, 108 patients were treated; 75 patients managed prior to and 33 after establishment of guidelines. One Jehovah’s Wittness patient was excluded from the newer group for refusing transfusions and subsequently died. Median age was similar at 45 years in both groups (range 19-86 and 21-81 respectively). Patients above 60 years were approximately 30% (23/75 and 10/32) and platelet count (29 and 30) were similar in both groups. In the earlier group, median white cell count (WBC) (4.2 and 2.2) and proportion of high risk (WBC >10,000/ml) patients (36% vs 21%) were higher. In the earlier group, induction regimen consisted of ATRA in combination with anthracycline (50, 66%), arsenic (12, 16%), other chemotherapy (8, 10%) or single agent ATRA in (5, 6%) patients. In contrast in the newer group, ATRA with ATO was the preferred induction regimen in 24 (75%) and anthracycline based treatment was used in 6 (18%) patients. 2 patients received ATRA alone.Overall the ED rate was higher in the earlier group with 19 patients (25%) dying in the first month. The causes of death were DIC (9), DS (7) and infection/MOF (3). 5 patients presented with large intracranial bleeds and were extremely ill. Excluding the patients that were referred late, the mortality was 18%; similar to some single institution studies but more than what is seen in clinical trials.After the institution of our algorithm, mortality was reduced to 9.4% (3/32 ED). Cause of ED was DS (2) and DIC (1). The incidence of severe DS (18% vs 6%) and sepsis (28% vs 16%) were lower in the newer group. The improved outcomes (25% vs 9.3%) is probably multifactorial due to lower number of high risk patients, more frequent arsenic based induction, use of streamlined guidelines and advice by dedicated APL experts.
Conclusion
Our experience shows that a streamlined treatment algorithm along with input from experts will result in better outcomes in this most curable hematological malignancy even at academic centers. We believe our experience warrants large scale implementation of our model and is presently approved as an ECOG/ACRIN trial.
Session topic: E-poster
Keyword(s): APL, Induction
Type: Publication Only
Background
APL is a highly curable malignancy with reported survival above 90% in many large co-operative group studies. Treatment of low and intermediate risk patients showed an expected survival of 99% with retinoic acid (ATRA)/Arsenic (ATO) combination versus 91 % with ATRA/chemotherapy at 2 years. These spectacular results are not evident in the general population. US SEER data showed that 1 and 5 year relative survival in APL patients is 71% and 65%. Studies from Swedish Cancer Registry and Brazil showed that early deaths (ED) can be approximately 30%. This is in contrast to observation in clinical trials where the early mortality is approximately 5%. Common causes of death are hemorrhagic complications (HC), differentiation syndrome (DS), infection and multi-organ failure (MOF). It is now agreed that the most common cause of treatment failure in APL is ED; and decreasing ED will improve population wide survival in this most curable leukemia. We report our institutional experience that showed a decrease in ED by using a streamlined set of guidelines and expert advice as needed.
Aims
To identify the impact of streamlined guidelines
Methods
We reviewed charts of patients with newly diagnosed APL and treated at our institution between January 2007 and August 2013 (earlier group). We compared these outcomes with those diagnosed from September 2013 to January 2016 (newer group) when we put in place a set of streamlined guidelines to improve ED. In addition to the guidelines, three faculty members with an interest in APL provided input as needed in the management of all newly diagnosed patients.
Results
From 01/2007 to 01/2016, 108 patients were treated; 75 patients managed prior to and 33 after establishment of guidelines. One Jehovah’s Wittness patient was excluded from the newer group for refusing transfusions and subsequently died. Median age was similar at 45 years in both groups (range 19-86 and 21-81 respectively). Patients above 60 years were approximately 30% (23/75 and 10/32) and platelet count (29 and 30) were similar in both groups. In the earlier group, median white cell count (WBC) (4.2 and 2.2) and proportion of high risk (WBC >10,000/ml) patients (36% vs 21%) were higher. In the earlier group, induction regimen consisted of ATRA in combination with anthracycline (50, 66%), arsenic (12, 16%), other chemotherapy (8, 10%) or single agent ATRA in (5, 6%) patients. In contrast in the newer group, ATRA with ATO was the preferred induction regimen in 24 (75%) and anthracycline based treatment was used in 6 (18%) patients. 2 patients received ATRA alone.Overall the ED rate was higher in the earlier group with 19 patients (25%) dying in the first month. The causes of death were DIC (9), DS (7) and infection/MOF (3). 5 patients presented with large intracranial bleeds and were extremely ill. Excluding the patients that were referred late, the mortality was 18%; similar to some single institution studies but more than what is seen in clinical trials.After the institution of our algorithm, mortality was reduced to 9.4% (3/32 ED). Cause of ED was DS (2) and DIC (1). The incidence of severe DS (18% vs 6%) and sepsis (28% vs 16%) were lower in the newer group. The improved outcomes (25% vs 9.3%) is probably multifactorial due to lower number of high risk patients, more frequent arsenic based induction, use of streamlined guidelines and advice by dedicated APL experts.
Conclusion
Our experience shows that a streamlined treatment algorithm along with input from experts will result in better outcomes in this most curable hematological malignancy even at academic centers. We believe our experience warrants large scale implementation of our model and is presently approved as an ECOG/ACRIN trial.
Session topic: E-poster
Keyword(s): APL, Induction
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