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Prothrombotic risk factors in children with acute lymphoblastic leukemia treated with delayed E. coli asparaginase
C Mauz-Körholz1, R Junker, U Göbel
1Department of Paediatric Haematology and Oncology, Heinrich-Heine University Medical Centre, Düsseldorf, Germany.
Insights
Prothrombotic risk factors did not increase thrombosis risk in childhood leukemia patients on the COALL protocol. Thrombosis events occurred in children without these inherited risk factors, suggesting treatment regimen influences risk.
Area of Science:
- Pediatric Hematology
- Oncology
- Thrombosis Research
Background:
- Hereditary prothrombotic risk factors are linked to venous thrombosis in children receiving E. coli asparaginase and steroids.
- The COALL study protocol treats childhood acute lymphoblastic leukemia (ALL).
Purpose of the Study:
- To investigate the role of prothrombotic risk factors in children with ALL treated under the COALL study protocol.
- To determine if inherited thrombophilia influences thrombosis risk in this specific pediatric ALL treatment context.
Main Methods:
- Prospective investigation of 108 consecutively recruited childhood ALL patients.
- Assessed prevalence of key prothrombotic risk factors: Factor V G1691A, Prothrombin G20210A, MTHFR TT677, Protein C, Protein S, Antithrombin deficiencies, and elevated Lipoprotein (a).
- Monitored for venous thromboembolism (VTE) events during treatment.
Main Results:
- Prevalence of tested prothrombotic risk factors was comparable to healthy Caucasian populations and other leukemia cohorts.
- Three out of 108 children (2.8%) experienced venous thromboembolism.
- None of the children who developed VTE carried any of the investigated prothrombotic risk factors.
Conclusions:
- Hereditary prothrombotic risk factors may not significantly contribute to thrombosis in childhood ALL patients treated with the COALL regimen.
- The treatment regimen itself might play a more critical role in the development of thrombosis than inherited coagulation disturbances.
- Further research is needed to elucidate the complex interplay between treatment, coagulation, and thrombosis in pediatric ALL.
Abstract:
Hereditary prothrombotic risk factors have been shown to increase the risk of venous thrombosis in children treated with the combination of E. coli asparaginase and steroids. In the present study the role of prothrombotic risk factors in children with ALL treated according to the COALL study protocol was investigated in 108 consecutively recruited childhood patients. The prevalence rates of prothrombotic risk factors [factor V G1691A mutation, the prothrombin G20210A variant, the TT677 methylenetetrahydrofolate reductase genotype, deficiencies of protein C, protein S, antithrombin, elevated lipoprotein (a)] in this cohort were within the range reported for healthy Caucasians, and comparable to previously reported data for other leukemic patients. Venous thromboembolism occurred in 3 of the 108 children (induction n = 1; reinduction n = 2: 2.8%), and none of these children carried a prothrombotic risk factor. The results of the present study, suggest that the role of hereditary and acquired disturbances of coagulation in the development of thromboses might depend on the treatment regimen.