title: An antithrombin replacement strategy during asparaginase therapy for acute lymphoblastic leukemia is associated with a reduction in thrombotic events.
abstract: Thrombosis is a well-recognized complication of asparaginase therapy for acute lymphoblastic leukemia (ALL), associated with the depletion of antithrombin (AT). Following a high incidence of thrombotic episodes during induction therapy for ALL in our tertiary referral center, we prospectively instituted a protocol of AT replacement. Forty-five consecutive adolescents and adults with ALL treated with asparaginase-containing phase I induction protocols were included in this observational study. Fifteen received standard therapy with no replacement; the subsequent 30 were managed with the protocol described. One or more low AT levels (<70 iu/dl) were recorded in 76% of patients in the cohort managed using the protocol, resulting them in receiving an AT replacement. There was a significant reduction in the incidence of thrombosis with this strategy (0/30 vs. 5/15, p < 0.001). We suggest that such a strategy should be studied in a prospective randomized sub-study within the context of a national ALL trial.
authors.affiliation: a Forth Valley Royal Hospital , Larbert , UK ;
authors.forename: Katrina
authors.initials: K
authors.lastname: Farrell
authors.affiliation: b Wishaw General Hospital , Wishaw , UK ;
authors.forename: Andrew
authors.initials: A
authors.lastname: Fyfe
authors.affiliation: c Glasgow Royal Infirmary , Glasgow , UK ;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Allan
authors.affiliation: d Beatson West of Scotland Cancer Centre, Gartnavel General Hospital , Glasgow , UK.
authors.forename: R Campbell
authors.initials: RC
authors.lastname: Tait
authors.affiliation: c Glasgow Royal Infirmary , Glasgow , UK ;
authors.forename: Mike
authors.initials: M
authors.lastname: Leach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D012189:Retrospective Studies; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000991:Antithrombins; D001215:Asparaginase
keywords: Acute lymphoblastic leukemia; antithrombin; asparaginase; thrombosis