OMITTING CYTARABINE FROM CHEMOTHERAPY FOR ACUTE PROMYELOCYTIC LEUKEMIA REDUCES TOXICITY AND NOT EFFICACY
(Abstract release date: 05/18/17)
EHA Library. Gavriilaki E. 05/18/17; 182412; PB1698
Dr. Eleni Gavriilaki
Contributions
Contributions
Abstract
Abstract: PB1698
Type: Publication Only
Background
The introduction of retinoic acid (ATRA) has changed the treatment paradigm in Acute Promyelocytic Leukemia (APL). Combination of ATRA plus anthracycline-based induction (AIDA) without cytarabine (AraC) has shown high efficacy in Spanish and Italian studies. However, early mortality resulting from coagulation disorders remains high. Furthermore, AraC administration during consolidation is questioned and often limited to high-risk patients.
Aims
We aim to compare the efficacy, tolerance and toxicity between 2 consecutive treatment protocols that differed in AraC administration during consolidation.
Methods
We studied clinical characteristics, prognostic factors, response to treatment, tolerance, toxicity and outcomes in APL patients treated in our Department during the last decade. All patients received induction with AIDA (Idarubicin x4, ATRA until remission) and 2-year maintenance therapy. Protocol 1 included 2 cycles of consolidation with anthracyclines/AraC. Protocol 2 was implemented the last 5 years and included 3 cycles of anthracyclines and AraC only in high-risk patients (PETHEMA LPA2005).
Results
APL was diagnosed in 35 patients, of whom 2 patients older than 80 years did not receive treatment and were not included in the analysis. The rest 18 male: 15 female patients aged 37 (10-75) years old presented at diagnosis with: thrombocytopenia (32), leukopenia (22), leukocytosis (6), impaired performance status/PS >2 (10), lactate dehydrogenase >400 IU (17), increased d-dimers (33), low fibrinogen (11), fibirinogen <1 mg/dl (5).
Five patients died during induction from severe differentiation syndrome (2), bleeding (2) and infection (1). In the multivariate analysis, these patients had significantly impaired PS (3, p=0.005), older age (median of 59 years, p=0.014) and lower fibrinogen (median of 0.9 mg/dl, p=0.05).
Among 28 patients eligible for the comparison, all patients achieved complete remission (CR=100%). Protocol 1 (AraC) was applied to 16 patients and 2 to 12 patients. Complete molecular remission was achieved after a median of 2 chemotherapies (1-3). Efficacy could not be compared between protocols because there was only 1 relapse in Protocol 2, refractory to chemotherapy, ATRA, arsenic trioxide and allogeneic transplantation. However, there were significant differences in tolerance and toxicity. Patients in Protocol 1 had significantly higher transfusion needs compared to Protocol 2(p<0.001): 9(2-15) versus 1(0-17) red blood cell and 11(3-32) versus 2(0-10) platelet transfusion. Duration of grade 4 leukopenia was significantly higher in Protocol 1 [16(5-19) versus 9(0-18) days, p=0.002]. The same was true for neutropenia (p=0.04) and resulted to higher infection rates in Protocol 1 (58% versus 17%, p=0.03), including 2 aspergilloses and 1 fatal sepsis. 10-year overall survival probability was 73.1%, with no difference between Protocols.
Conclusion
Our study confirms that early mortality is a significant issue in APL, in particular for older patients. AraC can be safely omitted from treatment of low- and intermediate-risk patients, resulting in significantly reduced toxicity.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): toxicity, Cytarabine, Acute Promyelocytic Leukemia
Abstract: PB1698
Type: Publication Only
Background
The introduction of retinoic acid (ATRA) has changed the treatment paradigm in Acute Promyelocytic Leukemia (APL). Combination of ATRA plus anthracycline-based induction (AIDA) without cytarabine (AraC) has shown high efficacy in Spanish and Italian studies. However, early mortality resulting from coagulation disorders remains high. Furthermore, AraC administration during consolidation is questioned and often limited to high-risk patients.
Aims
We aim to compare the efficacy, tolerance and toxicity between 2 consecutive treatment protocols that differed in AraC administration during consolidation.
Methods
We studied clinical characteristics, prognostic factors, response to treatment, tolerance, toxicity and outcomes in APL patients treated in our Department during the last decade. All patients received induction with AIDA (Idarubicin x4, ATRA until remission) and 2-year maintenance therapy. Protocol 1 included 2 cycles of consolidation with anthracyclines/AraC. Protocol 2 was implemented the last 5 years and included 3 cycles of anthracyclines and AraC only in high-risk patients (PETHEMA LPA2005).
Results
APL was diagnosed in 35 patients, of whom 2 patients older than 80 years did not receive treatment and were not included in the analysis. The rest 18 male: 15 female patients aged 37 (10-75) years old presented at diagnosis with: thrombocytopenia (32), leukopenia (22), leukocytosis (6), impaired performance status/PS >2 (10), lactate dehydrogenase >400 IU (17), increased d-dimers (33), low fibrinogen (11), fibirinogen <1 mg/dl (5).
Five patients died during induction from severe differentiation syndrome (2), bleeding (2) and infection (1). In the multivariate analysis, these patients had significantly impaired PS (3, p=0.005), older age (median of 59 years, p=0.014) and lower fibrinogen (median of 0.9 mg/dl, p=0.05).
Among 28 patients eligible for the comparison, all patients achieved complete remission (CR=100%). Protocol 1 (AraC) was applied to 16 patients and 2 to 12 patients. Complete molecular remission was achieved after a median of 2 chemotherapies (1-3). Efficacy could not be compared between protocols because there was only 1 relapse in Protocol 2, refractory to chemotherapy, ATRA, arsenic trioxide and allogeneic transplantation. However, there were significant differences in tolerance and toxicity. Patients in Protocol 1 had significantly higher transfusion needs compared to Protocol 2(p<0.001): 9(2-15) versus 1(0-17) red blood cell and 11(3-32) versus 2(0-10) platelet transfusion. Duration of grade 4 leukopenia was significantly higher in Protocol 1 [16(5-19) versus 9(0-18) days, p=0.002]. The same was true for neutropenia (p=0.04) and resulted to higher infection rates in Protocol 1 (58% versus 17%, p=0.03), including 2 aspergilloses and 1 fatal sepsis. 10-year overall survival probability was 73.1%, with no difference between Protocols.
Conclusion
Our study confirms that early mortality is a significant issue in APL, in particular for older patients. AraC can be safely omitted from treatment of low- and intermediate-risk patients, resulting in significantly reduced toxicity.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): toxicity, Cytarabine, Acute Promyelocytic Leukemia
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