Mediastinal Mass, Triglycerides Level Above 1000mg/Dl and Intensive Dexamethasone and Asparaginase Treatment Are Risk Factors for Cerebral Sinus Venous Thrombosis in Children Treated for Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon
Authors: El-Khoury Habib , Ghanem Khaled M , Mubarak Yaacoub , Tarek Nidale , El Solh Hassan , Chan Anthony K.C. , Aridi Carole , Abboud Miguel R. , Saab Raya , Muwakkit Samar A. 
Published: October 2019

Abstract
Background: Cerebral sinus venous thrombosis (CSVT) is a serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No universal consensus exists regarding its risk factors due to rarity of cases. The effect of CSVT on outcome is not limited to its own complications but extends to its possible negative impact on ALL therapy. Age above 10 years, T-cell immunophenotype and risk stratification (intermediate/high risk) were previously shown to be statistically significant risk factors for CSVT in our cohort of patients with an odds ratio of 3.56, 2.32 and 3.40 respectively and a P-Value of 0.03, 0.02 and 0.04 respectively (Ghanem et al. 2017).
Aims and Methods: This is a prospective study of a pediatric cohort of children between 1 and 18 years of age treated for Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon (CCCL) between 2007 and 2017 with a protocol adopted from St Jude TOT XV. The aim of this analysis is to study the effect of decreasing asparginase and dexamethasone doses on the incidence of CSVT in addition to studying the effect of the following potential risk factors: presence of mediastinal mass at diagnosis, triglycerides level above 1000mg/dL and elevated initial blast count.
In 2015, L-asparginase doses were decreased during induction from 10,000IU/m2/dose to 6,000IU/m2/dose and Dexamethasone doses were decreased from 12mg/m2/dose to 8mg/m2/dose for intermediate/high risk patients and from 8mg/m2/dose to 6mg/m2/dose for low risk patients. Patients were divided into two groups: group I for individuals treated between 2007 and 2015 and group I for individuals treated between 2015 and 2017.
Results: A total of 202 patients were recruited (Group I, N=126 and Group II, N=76). The incidence of CSVT was 10.3% in group I and 1.3 % in group II. Univariate analysis showed that, treatment with intensive dexamethasone and asparginase in group I was a significant risk factor for CSVT (OR: 9.3, 95% CI: 1.2 - 72, P=0.03). Initial mediastinal mass (OR: 19.3, 95% CI: 5.4 - 68.6, P<0.0001) and triglycerides level above 1000mg/dL (OR: 3.4, 95% CI: 0.98 - 12, P=0.05) were also associated with increased risk of CSVT. Initial peripheral blast count ≥10,000 (OR: 0.57, 95% CI: 0.19 - 1.7, P=0.31), ≥50,000 (OR: 0.7, 95% CI: 0.14-3.35, P=0.66), and ≥100,000 (OR: 1.53, 95% CI: 0.29-7.82, P=0.61) were not risk factors for CSVT in our cohort.
Conclusion: Decreasing the doses of dexamethasone and asparginase significantly lowered the risk of CSVT in our patient population. Initial mediatinal mass and triglycerides levels above 1000mg/dL during asaparginase therapy were significantly associated with increased risk of developing CSVT. If future studies confirm our findings, mediastinal mass and elevated triglycerides level may be considered amongst other factors predisposing to CSVT and may help identify candidates for thromboprophylaxis in the future.

Disclosures
No relevant conflicts of interest to declare.