Contributions
Abstract: PB1642
Type: Publication Only
Background
Combined chemotherapy increased over time cure rate in patients with acute lymphoblastic leukemia (ALL). Among other things, one of the direct adverse effects of chemotherapy is affecting hemostasis inducing thrombosis or bleeding. Hemostasis can also be affected indirectly by the appearance of infections secondary immunosuppression. It has been found that L Asparaginase induces thrombotic events by reducing antithrombin III, protein C, protein S and by inducing endothelial damage. Thrombotic events may result as a direct effect of the disease, may be the effect of chemotherapy or may be related with prothrombotic status of the patient.
Aims
To evaluate incidence and severity of thrombotic or bleeding events in paediatric patients with ALL during chemotherapy.
Methods
We considered all patients hospitalized for ALL in the Pediatrics Department of Clinical Institute Fundeni during 2010-2017 and received chemotherapy according to protocol ALL BFM 1995 and ALL BFM 2002, established after framing in the risk group.
Results
Over a period of 8 years in our department 280 patients with ALL received L-asparaginase in the induction phase. Neurological manifestation suggestive for bleeding or thrombotic events occurred in 9/280 (3,21 %) patients. 2 patients were treated according protocol ALL BFM 1995 and 7 patients were treated according to protocol ALL BFM 2002. M/F ratio was 4/5. Patients had at diagnosis between 3 and 15 years (median age 9 years). All patients had thrombotic events after starting administration of L Asparaginase during induction. Most had clinical symptoms after the fourth dose of L Asparaginase. Clinical manifestations were accompanied by hypofibrinogenemia (<100 mg/dl) especially in patients who experienced bleeding. The patients who experienced thrombosis had decreased levels of antithrombin III, protein C and increased D dimer levels. The diagnosis of cerebral venous sinus thrombosis (CVST) is typically based on clinical suspicion and imaging confirmation. At 5 of these patients neuroimaging test (CT and MR imaging) documented CVST after developing neurological symptoms; one of the patients suffered major complication (extended brain injury) and died. All patients with ALL and thrombotic events received low-molecular weight heparin (LMWH) for 3 to 6 months. A follow-up CT or MRI at 3 to 6 months after diagnosis was made to assess for recanalization of the occluded cortical vein/sinuses. Survival in the patients with CVST was 84.61%. 1 patient with ALL and hemostasis alteration had intracerebral hemorrhage (ICH) with rapid progressive neurological deterioration to death. 1 patient had pulmonary embolism associated with clotting disorders and severe sepsis and he died. 2 patients had clinical manifestation (headache, confusion and seizures) and clotting disorders (decreased levels of antithrombin III, protein C, fibrinogen and increased D dimer levels), but with normal brain imaging. Survival in the cohort was 77,7%.
Conclusion
Thrombotic events have occured in all patients during induction. Clinical manifestation were depending on location, size and duration of thrombosis, from headaches, seizures or focal neurological deficits. Severe sepsis association was an additionally risk factor for thrombotic and bleeding events in patients with ALL. Screening for genetic prothrombotic defects diagnosis prior to initiating chemotherapy may represent a way to reduce thrombotic or bleeding events and appropriate management of hemostasis disorders that occur during the treatment.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Thrombosis, Asparaginase, ALL
Abstract: PB1642
Type: Publication Only
Background
Combined chemotherapy increased over time cure rate in patients with acute lymphoblastic leukemia (ALL). Among other things, one of the direct adverse effects of chemotherapy is affecting hemostasis inducing thrombosis or bleeding. Hemostasis can also be affected indirectly by the appearance of infections secondary immunosuppression. It has been found that L Asparaginase induces thrombotic events by reducing antithrombin III, protein C, protein S and by inducing endothelial damage. Thrombotic events may result as a direct effect of the disease, may be the effect of chemotherapy or may be related with prothrombotic status of the patient.
Aims
To evaluate incidence and severity of thrombotic or bleeding events in paediatric patients with ALL during chemotherapy.
Methods
We considered all patients hospitalized for ALL in the Pediatrics Department of Clinical Institute Fundeni during 2010-2017 and received chemotherapy according to protocol ALL BFM 1995 and ALL BFM 2002, established after framing in the risk group.
Results
Over a period of 8 years in our department 280 patients with ALL received L-asparaginase in the induction phase. Neurological manifestation suggestive for bleeding or thrombotic events occurred in 9/280 (3,21 %) patients. 2 patients were treated according protocol ALL BFM 1995 and 7 patients were treated according to protocol ALL BFM 2002. M/F ratio was 4/5. Patients had at diagnosis between 3 and 15 years (median age 9 years). All patients had thrombotic events after starting administration of L Asparaginase during induction. Most had clinical symptoms after the fourth dose of L Asparaginase. Clinical manifestations were accompanied by hypofibrinogenemia (<100 mg/dl) especially in patients who experienced bleeding. The patients who experienced thrombosis had decreased levels of antithrombin III, protein C and increased D dimer levels. The diagnosis of cerebral venous sinus thrombosis (CVST) is typically based on clinical suspicion and imaging confirmation. At 5 of these patients neuroimaging test (CT and MR imaging) documented CVST after developing neurological symptoms; one of the patients suffered major complication (extended brain injury) and died. All patients with ALL and thrombotic events received low-molecular weight heparin (LMWH) for 3 to 6 months. A follow-up CT or MRI at 3 to 6 months after diagnosis was made to assess for recanalization of the occluded cortical vein/sinuses. Survival in the patients with CVST was 84.61%. 1 patient with ALL and hemostasis alteration had intracerebral hemorrhage (ICH) with rapid progressive neurological deterioration to death. 1 patient had pulmonary embolism associated with clotting disorders and severe sepsis and he died. 2 patients had clinical manifestation (headache, confusion and seizures) and clotting disorders (decreased levels of antithrombin III, protein C, fibrinogen and increased D dimer levels), but with normal brain imaging. Survival in the cohort was 77,7%.
Conclusion
Thrombotic events have occured in all patients during induction. Clinical manifestation were depending on location, size and duration of thrombosis, from headaches, seizures or focal neurological deficits. Severe sepsis association was an additionally risk factor for thrombotic and bleeding events in patients with ALL. Screening for genetic prothrombotic defects diagnosis prior to initiating chemotherapy may represent a way to reduce thrombotic or bleeding events and appropriate management of hemostasis disorders that occur during the treatment.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Thrombosis, Asparaginase, ALL