title: Incidence and risk factors for Central Nervous System thrombosis in paediatric acute lymphoblastic leukaemia during intensive asparaginase treatment: a single-centre cohort study.
abstract: Central Nervous System (CNS) thrombosis is a complication of acute lymphoblastic leukaemia (ALL) treatment that is potentially associated with significant morbidity and neurological sequelae. Its presumably multifactorial aetiology is poorly characterized. We conducted a single-centre, retrospective cohort study on 346 ALL paediatric patients (1-16 years old) treated with asparaginase intensive Dana Farber Cancer Institute (DFCI) protocols from 1998 to 2011. The incidence, risk factors and outcome of CNS thrombosis were evaluated. CNS thrombosis occurred in 3·8% (13/346) of the patients (95% confidence interval 2·0-6·3%). Twelve events were diagnosed during intensification, all of which resolved within 2 weeks without neurological sequelae or significant impact in survival. Obesity (body mass index above 95th percentile) and asparaginase formulation were the only factors associated with CNS thrombosis, with an increase in the odds of event in obese patients [odds ratio (OR) = 3·37; P = 0·064] and a reduction in patients receiving Erwinia asparaginase (OR = 0·12; P = 0·018). No association could be demonstrated for age, gender, DFCI risk-group, ALL phenotype, steroid or doxorubicin use, central venous line use or CNS radiotherapy. CNS thrombosis is a rare but manageable adverse event without significant sequelae or detrimental effects in survival. Increased awareness is recommended in obese patients particularly during intensive asparaginase use.
authors.affiliation: Paediatric Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Lisbon, Portugal.
authors.forename: Ximo
authors.initials: X
authors.lastname: Duarte
authors.affiliation: Clinical Research Unit, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Lisbon, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Esteves
authors.affiliation: Paediatric Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Lisbon, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Neto
authors.affiliation: Paediatric Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Lisbon, Portugal.
authors.forename: Filomena
authors.initials: F
authors.lastname: Pereira
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage; D002490:Central Nervous System / Q000098:blood supply*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009765:Obesity / Q000150:complications; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase
keywords: acute lymphoblastic leukaemia; asparaginase; central nervous system thrombosis; risk factors, paediatric oncology