title: Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia.
abstract: This open-label, dose-escalation study evaluated the safety and efficacy of single-agent gemtuzumab ozogamicin, a humanized anti-CD33 antibody-targeted chemotherapeutic agent, for pediatric patients with multiple relapsed or primary refractory acute myeloid leukemia (AML). Twenty-nine children 1 to 16 years of age (relapsed disease, 19; refractory disease, 10) received gemtuzumab ozogamicin ranging from 6 to 9 mg/m2 per dose for 2 doses (separated by 2 weeks) infused over 2 hours. All patients had anticipated myelosuppression. Other toxicities included grade 3/4 hyperbilirubinemia (7%) and elevated hepatic transaminase levels (21%); the incidence of grade 3/4 mucositis (3%) or sepsis (24%) was relatively low. One patient treated at 9 mg/m2 developed veno-occlusive disease (VOD) of the liver and defined the dose-limiting toxicity. Thirteen patients underwent hematopoietic stem-cell transplantation less than 3.5 months after the last dose of gemtuzumab ozogamicin; 6 (40%) developed VOD. Eight of 29 (28%) patients achieved overall remission. Remissions were comparable in patients with refractory (30%) and relapsed (26%) disease. Mean multidrug resistance-protein-mediated drug efflux was significantly lower in the leukemic blasts of patients achieving remission (P < .005). Gemtuzumab ozogamicin was relatively well tolerated at 6 mg/m2 for 2 doses and was equally effective in patients with refractory and relapsed disease. Further studies in combination with standard induction therapy for childhood AML are warranted.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 2M51, Bunting-Blaustein Cancer Research Bldg, 1650 Orleans St, Baltimore, MD 21231, USA. arcecro@jhmi.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Jane
authors.initials: J
authors.lastname: Sande
authors.forename: Beverly
authors.initials: B
authors.lastname: Lange
authors.forename: Kevin
authors.initials: K
authors.lastname: Shannon
authors.forename: Janet
authors.initials: J
authors.lastname: Franklin
authors.forename: Raymond
authors.initials: R
authors.lastname: Hutchinson
authors.forename: Terry A
authors.initials: TA
authors.lastname: Vik
authors.forename: David
authors.initials: D
authors.lastname: Flowers
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
authors.forename: Mark S
authors.initials: MS
authors.lastname: Berger
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Sherman
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
authors.forename: Irwin
authors.initials: I
authors.lastname: Bernstein
authors.forename: Eric L
authors.initials: EL
authors.lastname: Sievers
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001752:Blast Crisis; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D000079982:Gemtuzumab; D018380:Hematopoietic Stem Cell Transplantation; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D020714:Maximum Tolerated Dose; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000379:methods*; D063268:Sialic Acid Binding Ig-like Lectin 3
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab