title: l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial.
abstract: l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .
authors.affiliation: Institut d'Hemato-Oncologie pédiatrique, Hospices civils de Lyon, Université Claude Bernard, France. carine.halfon-domenech@chu-lyon.fr
authors.forename: Carine
authors.initials: C
authors.lastname: Domenech
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chabaud
authors.forename: Andre
authors.initials: A
authors.lastname: Baruchel
authors.forename: François
authors.initials: F
authors.lastname: Gueyffier
authors.forename: Françoise
authors.initials: F
authors.lastname: Mazingue
authors.forename: Anne
authors.initials: A
authors.lastname: Auvrignon
authors.forename: Selim
authors.initials: S
authors.lastname: Corm
authors.forename: Herve
authors.initials: H
authors.lastname: Dombret
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.forename: Claire
authors.initials: C
authors.lastname: Galambrun
authors.forename: Françoise
authors.initials: F
authors.lastname: Huguet
authors.forename: Faezeh
authors.initials: F
authors.lastname: Legrand
authors.forename: Françoise
authors.initials: F
authors.lastname: Mechinaud
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Irène
authors.initials: I
authors.lastname: Philip
authors.forename: David
authors.initials: D
authors.lastname: Liens
authors.forename: Yann
authors.initials: Y
authors.lastname: Godfrin
authors.forename: Dominique
authors.initials: D
authors.lastname: Rigal
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D019149:Bioreactors; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D001215:Asparaginase