Contributions
Abstract: PB1744
Type: Publication Only
Background
An integral part of the initial treatment of acute promyelocytic leukemia (APL) is a supportive treatment of hemorrhagic diathesis. Early death (ED) either before or during induction treatment remains the most frequent cause of failure in the treatment of APL. The induction death rate within the first month of ATRA treatment ranged between 5%–10% in clinical trials, however in real-life non-selected patients the ED rate ranged between 17%–30%. The most frequent reason of ED is fatal intracranial (57%–62%) or alveolar hemorrhage or both.
Aims
Some adverse prognostic factors are known being in correlation with ED and some are still being studied. We analyzed biologic and laboratory characteristics of patients with APL in relation to ED.
Methods
Eligible patients were adults, at least 18 years of age with de novo APL. Risk group was set according to Sanz et al predicting model. ED was the death from any cause during induction. Patients were treated progressively over the years by the Spanish treatment protocol (LPA96, LPA99, LPA2005) and from the June 2017 by the Intergroup Study Protocol (GIMEMA + DSIL, APL 0406), which means that the induction treatment till June 2017 consists of ATRA and anthracycline for all risk groups and thereafter consists of ATRA and ATO for low and intermediate risk group, while high risk group continues the induction ATRA + anthracycline + cytarabine. All patients were analyzed for: sex, age, leukocytes, thrombocytes, blasts in peripheral blood (PB) and bone marrow (BM), lactate dehydrogenase (LDH), HLA-DR and CD56 expression, fibrinogen, PT and APTT, additional chromosomal abnormalities and PML/RARA type of transcript in relation to ED. For survival evaluation were used log-rank test (Kaplan-Meier) and Fisher exact test was used for early death risk factor analysis.
Results
24 patients with APL were diagnosed and treated from 10/2002 to 1/2018. Two patients died till 12 hours after admission to the hospital (46 years old and 20 years old woman with initial clinical signs of intracerebral bleeding at the time of initial investigation, both started treatment of APL) and they were excluded from the survival assessment. We observed totally six ED (25%), representing 66.7% of total APL deaths. Five (25%) of them due to hemorrhagic event, four (16.7%) patients had intracerebral hemorrhage and 1 patient had intrapulmonary hemorrhage. One patient died of tumor lysis syndrome. 17 (70.8%) patients achieved first complete molecular remission, two patients died in relapse and one woman had primary myelosarcoma of the breasts, APL subtype, she didn´t achieved complete remission and refused any treatment after induction as well and died. At median time of follow-up 46 month (0.16–159 months) the estimated 3-year OS and RFS were 77.0% CI 95% (59.3%–94.7%) and 71.9% CI 95% (52.7%–91.1%) respectively. In univariate analysis the prognostic factor that most influenced survival were the number of leukocytes ≥ 10x109/l (p=0.018), blasts in PB ≥ 70% (p=0.007), PT-INR > 1.5 (p=0.001), APTT ≥ 35s (p=0.014). Risk factors associated with early death were: Le ≥ 10x109/l (p=0.015), blasts in PB ≥ 70% (p=0.001), PT-INR > 1.5 (p=0.001), LDH > 4μkat/l (p=0.002) and presence of bcr3 transcript (p=0.033).
Conclusion
Hemorrhagic events are the main cause of ED. Quick transport to hematologic center treating APL, recognizing high risk patients and supportive treatment are crucial for favorable outcome. Outcome of APL patients in our center is comparable to the results reported as real life data or from cancer registries.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Acute Promyelocytic Leukemia, Hemorrhage, Survival, Treatment-related mortality
Abstract: PB1744
Type: Publication Only
Background
An integral part of the initial treatment of acute promyelocytic leukemia (APL) is a supportive treatment of hemorrhagic diathesis. Early death (ED) either before or during induction treatment remains the most frequent cause of failure in the treatment of APL. The induction death rate within the first month of ATRA treatment ranged between 5%–10% in clinical trials, however in real-life non-selected patients the ED rate ranged between 17%–30%. The most frequent reason of ED is fatal intracranial (57%–62%) or alveolar hemorrhage or both.
Aims
Some adverse prognostic factors are known being in correlation with ED and some are still being studied. We analyzed biologic and laboratory characteristics of patients with APL in relation to ED.
Methods
Eligible patients were adults, at least 18 years of age with de novo APL. Risk group was set according to Sanz et al predicting model. ED was the death from any cause during induction. Patients were treated progressively over the years by the Spanish treatment protocol (LPA96, LPA99, LPA2005) and from the June 2017 by the Intergroup Study Protocol (GIMEMA + DSIL, APL 0406), which means that the induction treatment till June 2017 consists of ATRA and anthracycline for all risk groups and thereafter consists of ATRA and ATO for low and intermediate risk group, while high risk group continues the induction ATRA + anthracycline + cytarabine. All patients were analyzed for: sex, age, leukocytes, thrombocytes, blasts in peripheral blood (PB) and bone marrow (BM), lactate dehydrogenase (LDH), HLA-DR and CD56 expression, fibrinogen, PT and APTT, additional chromosomal abnormalities and PML/RARA type of transcript in relation to ED. For survival evaluation were used log-rank test (Kaplan-Meier) and Fisher exact test was used for early death risk factor analysis.
Results
24 patients with APL were diagnosed and treated from 10/2002 to 1/2018. Two patients died till 12 hours after admission to the hospital (46 years old and 20 years old woman with initial clinical signs of intracerebral bleeding at the time of initial investigation, both started treatment of APL) and they were excluded from the survival assessment. We observed totally six ED (25%), representing 66.7% of total APL deaths. Five (25%) of them due to hemorrhagic event, four (16.7%) patients had intracerebral hemorrhage and 1 patient had intrapulmonary hemorrhage. One patient died of tumor lysis syndrome. 17 (70.8%) patients achieved first complete molecular remission, two patients died in relapse and one woman had primary myelosarcoma of the breasts, APL subtype, she didn´t achieved complete remission and refused any treatment after induction as well and died. At median time of follow-up 46 month (0.16–159 months) the estimated 3-year OS and RFS were 77.0% CI 95% (59.3%–94.7%) and 71.9% CI 95% (52.7%–91.1%) respectively. In univariate analysis the prognostic factor that most influenced survival were the number of leukocytes ≥ 10x109/l (p=0.018), blasts in PB ≥ 70% (p=0.007), PT-INR > 1.5 (p=0.001), APTT ≥ 35s (p=0.014). Risk factors associated with early death were: Le ≥ 10x109/l (p=0.015), blasts in PB ≥ 70% (p=0.001), PT-INR > 1.5 (p=0.001), LDH > 4μkat/l (p=0.002) and presence of bcr3 transcript (p=0.033).
Conclusion
Hemorrhagic events are the main cause of ED. Quick transport to hematologic center treating APL, recognizing high risk patients and supportive treatment are crucial for favorable outcome. Outcome of APL patients in our center is comparable to the results reported as real life data or from cancer registries.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Acute Promyelocytic Leukemia, Hemorrhage, Survival, Treatment-related mortality