Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management

Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26694. Epub 2017 Jun 29.

Abstract

Background: Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of childhood 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 characteristics, clinical management, and outcomes were studied.

Results: The incidence of CSVT was 6.2% (95% confidence interval [CI]: 3.4-10.4). Using univariate 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 multivariate 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 neurological recovery.

Conclusions: CSVT is an important complication of childhood ALL therapy. Postinduction combined 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.

MeSH terms

  • Adolescent
  • Adult
  • Asparaginase / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Infant
  • Logistic Models
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Retrospective Studies
  • Risk Factors
  • Sinus Thrombosis, Intracranial / drug therapy
  • Sinus Thrombosis, Intracranial / etiology*
  • Young Adult

Substances

  • Heparin, Low-Molecular-Weight
  • Asparaginase