Purpose: NUDT15 genetic polymorphism is known to be associated with frequent hematopoietic toxicities during acute lymphoblastic leukemia (ALL) mercaptopurine therapy. The aim of this study is to test this association in a group of Syrian children with ALL, in addition to quantify the prevalence of the corresponding SNP in patient population. Patients and Methods: This is a retrospective study that included all children with acute lymphoblastic leukemia reaching at least 6 months of maintenance therapy between January 2018 and May 2020 at two recruitment sites in Damascus, Syria. The NUDT15 rs116855232 genetic polymorphism was performed and linked to four clinical factors: mercaptopurine dose intensity, early onset leukopenia, hepatotoxicity and therapy interruption. Results: A total of 92 patients were enrolled (63.04% low-risk, 25% intermediate-risk and 11.96% high-risk). The TC genotype was found in 5 patients (5.4%) and the TT genotype was found in 1 patient (1.08%), with the following allele frequency: C=0.961 and T=0.038. The mercaptopurine dose intensity was 81.98%, 65.85% and 4.99% for the genotypes CC, TC and TT respectively (P: 0.0174). A significant association was found between early onset neutropenia and NUDT15 polymorphism (TC or TT), OR: 6.82 (95% CI: 1.22-38.11, P: 0.043). No association was found between NUDT15 polymorphism and therapy interruption or hepatotoxicity. Conclusion: Our study confirms that NUDT15 rs116855232 polymorphism is associated with mercaptopurine hematopoietic toxicity but not with hepatotoxicity or therapy interruption in a population of Syrian children with ALL. The incidence seems to be higher than neighboring countries.

Background: Cerebral Sinus Venous Thrombosis (CSVT) is one of many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, consensus management, no recommendations exist to target the population at risk. Methods: This is a retrospective chart review of 229 consecutive patients diagnosed with ALL and aged 1–21 years, treated at the Children’s Cancer Institute (CCI) between October 2007 and February 2017. Results: The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high risk disease, maximum Triglyceride (TG) level of > 615 mg/dL, presence of mediastinal mass, and larger body surface area. With multivariate analysis, the only statistically significant risk factors were maximum TG level, body surface area (BSA), presence of mediastinal mass, and risk stratification (intermediate/high risk). Conclusion: Our study was able to unveil TG level of > 615 mg/dL, mediastinal mass, and a larger body surface area as novel risk factors that have not been previously discussed in the literature.