title: Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia.
abstract: Mannose-binding lectin (MBL)-deficient children with cancer may benefit from substitution of the innate immune protein MBL during chemotherapy-induced neutropaenia. We determined the safety and pharmacokinetics of MBL substitution in a phase II study in MBL-deficient children. Twelve MBL-deficient children with cancer (aged 0-12 years) received infusions of plasma-derived MBL once, or twice weekly during a chemotherapy-induced neutropaenic episode (range: 1-4 weeks). Four patients participated multiple times. Target levels of 1.0 microg/ml were considered therapeutic. In total, 65 MBL infusions were given. No MBL-related adverse reactions were observed, and the observed trough level was 1.06 microg/ml (range: 0.66-2.05 microg/ml). Pharmacokinetics were not related to age after correction for body weight. The half-life of MBL, for a child of 25 kg, was 36.4h (range: 23.7-66.6h). No anti-MBL antibodies were measured 4 weeks after each MBL course. Substitution therapy with MBL-SSI twice weekly was safe and resulted in trough levels considered protective.
authors.affiliation: Emma Children's Hospital, Academic Medical Center, Room G8-205, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. f.n.frakking@amc.uva.nl
authors.forename: Florine N J
authors.initials: FN
authors.lastname: Frakking
authors.forename: Nannette
authors.initials: N
authors.lastname: Brouwer
authors.forename: Marianne D
authors.initials: MD
authors.lastname: van de Wetering
authors.forename: Ilona Kleine
authors.initials: IK
authors.lastname: Budde
authors.forename: Paul F W
authors.initials: PF
authors.lastname: Strengers
authors.forename: Alwin D
authors.initials: AD
authors.lastname: Huitema
authors.forename: Inga
authors.initials: I
authors.lastname: Laursen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.forename: Koert M
authors.initials: KM
authors.lastname: Dolman
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D037601:Mannose-Binding Lectin / Q000009:adverse effects* / Q000097:blood / Q000172:deficiency; D009503:Neutropenia / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D018579:Patient Selection; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D037601:Mannose-Binding Lectin