Received: 20 January 2017 Revised: 16 May 2017 Accepted: 30 May 2017 DOI: 10.1002/pbc.26694 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology RESEARCH ARTICLE Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management Khaled M. Ghanem 1 Raghida M. Dhayni 1 Carol Al-Aridi 1 Nidale Tarek 1 Hani Tamim 2 Anthony K. C. Chan 3 Raya Saab 1 Miguel R. Abboud 1 Hassan El-Solh 1 Samar A. Muwakkit 1 1 Department of Pediatrics and Adolescent Medicine, Hematology Oncology Service, Chil- dren’s Cancer Center of Lebanon, American University of Beirut, Beirut, Lebanon 2 Department of Internal Medicine, American University of Beirut, Beirut, Lebanon 3 Department of Pediatrics, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada Correspondence Samar Muwakkit, Department of Pediatrics and Adolescent Medicine, Hematology Oncology Service, Children’s Cancer Center of Lebanon, American University of Beirut Medical Center, Clemenceau Street. BLD 56, 1st floor PO Box 11-0236, Beirut, Lebanon. E-mail: sm03@aub.edu.lb Abstract Background: Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of child- hood acute lymphoblastic leukemia (ALL) therapy. No available consensus exists regarding its risk factors and appropriate management due to the rarity of cases. Procedures: Out of 209 ALL patients aged 1–21 years treated at the Children’s Cancer Center of Lebanon between May 2002 and May 2015, 13 developed CSVT during therapy. Patient charac- teristics, clinical management, and outcomes were studied. Results: The incidence of CSVT was 6.2% (95% confidence interval [CI]: 3.4–10.4). Using univari- ate analysis, increased risk of CSVT was observed with age >10 years (odds ratio [OR]: 3.56, 95% CI: 1.13–11.2), T-cell immunophenotype (OR: 4.14, 95% CI: 1.16–14.7), and intermediate/high risk disease (OR: 3.4, 95% CI: 1.03–11.7). The only statistically significant risk factor by multi- variate analysis was the treatment as per the intermediate-/high-risk protocol (HR: 15.6, 95% CI: 1.43–171.3). Most cases (77%) occurred in the postinduction phases of treatment while receiving a combination of asparaginase and dexamethasone rather than prednisone. Treatment with low molecular weight heparin (LMWH) for a minimum of 3 months and until significant radiological improvement is observed resulted in 100% survival rate. All but one patient had complete neuro- logical recovery. Conclusions: CSVT is an important complication of childhood ALL therapy. Postinduction com- bined asparaginase and dexamethasone intensive treatment for intermediate-/high-risk patients was the most important risk factor. Treatment with LMWH for a minimum of 3 months, and until asparginase therapy is over, with major radiological improvement seems to be effective and feasible. KEYWORDS asparaginase, cerebral sinus venous thrombosis, childhood ALL, steroids 1 INTRODUCTION Thrombosis is a potential complication during the treatment course of childhood acute lymphoblastic leukemia (ALL) with varying reported incidence of 1–37% in different patient populations and treatment protocols. 1 The effect of thrombosis on outcome is not limited to its Abbreviations: 6-MP, 6-mercaptopurine; ALL, acute lymphoblastic leukemia; ASP, asparaginase; AT, antithrombin; CI, confidence interval; CSVT, cerebral sinus venous thrombosis; CT, computed tomography; EFS, event-free survival; ICH, intracranial hemorrhage; IM, intramuscularly; LMWH, low molecular weight heparin; NOPHO, Nordic Society of Pediatric Hematology and Oncology; OS, overall survival own complications but extends to its possible negative impact on ALL treatment. 2 Cerebral sinus venous thrombosis (CSVT) is one of the most risky sites of involvement due to a considerable mortality rate of 8–13% and possible long-term neurological sequelae. 3 There is no strong evidence behind our current clinical practice due to the rarity of cases and the difficulty to implement prospective studies. Many previ- ous studies have tried to define high-risk groups and to suggest pro- phylaxis and treatment strategies without consistent results. In this manuscript, we report our single-institution clinical experience with diagnosis, management, and outcome of CSVT as a complication of childhood ALL treatment over a period of 13 years. Pediatr Blood Cancer. 2017;e26694. c  2017 Wiley Periodicals, Inc. 1 of 6 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.26694