title: Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group.
abstract: OBJECTIVE
  While gemtuzumab ozogamicin (GTMZ) is commonly used in the treatment of acute myeloid leukemia (AML) in combination with standard chemotherapy agents, the pediatric maximum-tolerated dose (MTD) of GMTZ in combination with chemotherapy has not been determined.
  
  
  METHODS
  The Children's Oncology Group AAML00P2 trial sought to define the MTD of GMTZ in combination with cytarabine and mitoxantrone and cytarabine and l-asparaginase chemotherapy regimens.
  
  
  RESULTS
  The MTD for GMTZ in combination with cytarabine and mitoxantrone was 3 mg/m(2) while the MTD in combination with cytarabine and l-asparaginase was 2 mg/m(2). Toxicities observed in both treatment regimens were typical of those seen in the relapsed AML setting and consisted primarily of infectious complications. The overall remission response rate (mean +/- SE) was 45% +/- 15% and the 1 year event-free survival and overall survival estimates were 38% +/- 14% and 53% +/- 15%, respectively.
  
  
  CONCLUSIONS
  This trial determined the pediatric MTD for GMTZ with two commonly used AML chemotherapy combinations. Based on these results, an ongoing phase III trial conducted within the Children's Oncology Group is evaluating the effect of GMTZ when added to standard AML therapy.
authors.affiliation: Children's Hospital of Philadelphia, Center for Clinical Epidemiology/Biostatistic, 3615 Civic Center Blvd, 916G ARC, Philadelphia, PA 19104-4318, USA. raplenc@mail.med.upenn.edu
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Lange
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hurwitz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wells
authors.forename: Irwin
authors.initials: I
authors.lastname: Bernstein
authors.forename: Patrick
authors.initials: P
authors.lastname: Buckley
authors.forename: Kathleen
authors.initials: K
authors.lastname: Krimmel
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
authors.forename: Eric L
authors.initials: EL
authors.lastname: Sievers
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D000079982:Gemtuzumab; D008942:Mitoxantrone; D001215:Asparaginase