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Older age, asparaginase treatment associated with thromboembolism in pediatric ALL
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Thromboembolism appeared to be a common adverse event in children and adolescents receiving treatment for acute lymphoblastic leukemia, according to the results of a prospective study conducted by the Nordic Society of Pediatric Hematology and Oncology.
Based on these findings, the influence of asparaginase on thromboembolism requires further study, according to the researchers.
“Modern treatment of ALL gives OS rates of more than 80%; however, chemotherapy is associated with several toxicities and complications, including venous and arterial thromboembolism,” Ruta Tuckuviene, MD, pediatrician at Aalborg University Hospital in Denmark, and colleagues wrote. “A major objective today is to prevent acute toxicities, which may have an impact on scheduled ALL therapy and which subsequently may have a negative influence on OS in children with ALL.”
Tuckuviene and colleagues sought to observe the cumulative incidence of thromboembolism in children with ALL, as well as the outcomes and risk factors in this patient population.
The researchers conducted a prospective study of children and adolescents from Nordic countries diagnosed with ALL between 2008 and 2013.
All children received treatment according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 protocol, comprised of induction therapy with dexamethasone or prednisone, followed by continued treatment based on risk designation.
The study included data from 1,038 children, 63 of whom experienced thromboembolism (cumulative incidence, 6.1%; 95% CI, 4.8-7.7). Fifty-two of the patients who experienced thromboembolism were receiving asparaginase.
The highest cumulative incidence occurred among patients aged 15 to 17 years (20.5%; 95% CI, 12.6-29.7). Based on these data, age between 15 years and 17 years appeared associated with an increased risk for thromboembolism in a multivariate analysis (adjusted HR = 4; 95% CI, 2.1-7.7).
The researchers further observed a thromboembolism-associated 30-day case fatality rate of 6.4% (95% CI, 1.8-15.5). Thromboembolism-related truncation of asparaginase therapy occurred in 36.2% of patients (n = 21).
Fifty-eight patients with thromboembolism received anticoagulation therapy, two of whom experienced major bleeding. Minor hemorrhaging occurred in two patients.
Children treated with low–molecular-weight heparin did not experience major bleeding.
“Our findings indicate that thromboembolism is a frequent and potentially severe complication of ALL treatment and associated with older age,” Tuckuviene and colleagues wrote. “The possible impact of asparaginase truncation must be evaluated in future studies.” – by Cameron Kelsall
Reference:
Tuckuviene R, et al. J Thromb Haematos. 2016;doi:10.1111/jth.13236.
Disclosure: The researchers report no relevant financial disclosures.