title: The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols.
abstract: The optimal management of asparaginase-associated thrombotic complications is not well-defined. We report the features, management and outcome of paediatric (ages 0-18years) and adult (18-50years) patients with acute lymphoblastic leukaemia (ALL) with asparaginase-related venous thromboembolic events (VTE) treated at Dana-Farber Cancer Institute on clinical trials for newly diagnosed ALL between 1991-2008. Of 548 patients, 43 (8%) had VTE, including 27/501 (5%) paediatric and 16/47 (34%) adult patients. Sinus venous thrombosis occurred in 1·6% of patients. Age was the only significant predictor of VTE, with those aged >30years at very high risk (VTE rate 42%). 74% of patients received low molecular weight heparin after VTE. Complications of anticoagulation included epistaxis (9%), bruising (2%) and, in two adult patients, major bleeding. Thirty patients (70%) ultimately received at least 85% of the intended doses of asparaginase. 33% of patients experienced recurrent VTE (paediatric 17% vs. adults 47%, P=0·07). The 48-month event-free survival for patients with VTE was 85±6% compared with 88±2% for those without VTE (P=0·36). This study confirms that, after VTE, asparaginase can be restarted with closely monitored anticoagulation after imaging demonstrates clot stabilization or improvement. With this management strategy, a history of VTE does not appear to adversely impact prognosis.
authors.affiliation: Pediatric Hematology/Oncology, Children's Hospital Boston, Dana-Farber Cancer Institute Harvard Medical School Biostatistics, Dana-Farber Cancer Institute Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Rachael.Grace@childrens.harvard.edu
authors.forename: Rachael F
authors.initials: RF
authors.lastname: Grace
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dahlberg
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Sallan
authors.forename: Jean M
authors.initials: JM
authors.lastname: Connors
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Deangelo
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D001215:Asparaginase