title: Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia.
abstract: OBJECTIVE
  Myeloablative allogeneic stem cell transplantation (SCT) has been successful in the treatment of childhood acute myeloid leukemia (AML), but may be associated with significant toxicity and recurrent disease. Reduced-intensity allogeneic SCT may offer a less toxic approach to patients with AML. Targeted immunotherapy with gemtuzumab ozogamicin has been shown to be safe, well tolerated in children, and, as a single agent, gemtuzumab ozogamicin has induced responses in 30% of patients with recurrent CD33+ AML. There are no safety data with gemtuzumab ozogamicin post allogeneic SCT in children. Therefore, we explored the feasibility and toxicity of targeted immunotherapy following reduced-intensity allogeneic SCT in children with CD33+ AML.
  
  
  METHODS
  Eight patients with CD33+ AML received a reduced-intensity allogeneic SCT following fludarabine 30 mg/m2 for 6 days and busulfan 3.2 mg/kg (<4 years, 4 mg/kg/d) for 2 days. Donor sources included six 6/6 HLA-matched related peripheral blood stem cells, one 6/6 sibling cord blood, and one 4/6 unrelated cord blood.
  
  
  RESULTS
  Day 30 and day 60 donor chimerisms in seven of eight evaluable patients were 96 +/- 2% (n = 7) and 94 +/- 3% (n = 6), respectively. Five of six patients (too early for one patient) received two doses of gemtuzumab ozogamicin and one patient received only one dose. After each dose, all patients developed grade 4 neutropenia, with recovery on median days 16 and 13, respectively, after dose 1 and dose 2. Grade 4 thrombocytopenia was only observed in 2 of 11 gemtuzumab ozogamicin courses. No patients have developed dose-limiting toxicity secondary to gemtuzumab ozogamicin.
  
  
  CONCLUSIONS
  The administration of gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with average risk AML is feasible and well tolerated with minimal toxicity. The maximal tolerated dose has yet to be determined for gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with CD33+ AML. Additional studies in a larger group of patients will be required to adequately assess the safety of this approach.
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York 10032, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Roman
authors.forename: Erin
authors.initials: E
authors.lastname: Cooney
authors.forename: Lauren
authors.initials: L
authors.lastname: Harrison
authors.forename: Olga
authors.initials: O
authors.lastname: Militano
authors.forename: Karen
authors.initials: K
authors.lastname: Wolownik
authors.forename: Ria
authors.initials: R
authors.lastname: Hawks
authors.forename: Sandi
authors.initials: S
authors.lastname: Foley
authors.forename: Prakash
authors.initials: P
authors.lastname: Satwani
authors.forename: Elif
authors.initials: E
authors.lastname: Unal
authors.forename: Monica
authors.initials: M
authors.lastname: Bhatia
authors.forename: Brigid
authors.initials: B
authors.lastname: Bradley
authors.forename: Gustavo
authors.initials: G
authors.lastname: Del Toro
authors.forename: Diane
authors.initials: D
authors.lastname: George
authors.forename: James
authors.initials: J
authors.lastname: Garvin
authors.forename: Carmella
authors.initials: C
authors.lastname: van de Ven
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000293:Adolescent; D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis*; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D000079982:Gemtuzumab; D006086:Graft vs Host Disease / Q000517:prevention & control; D006650:Histocompatibility Testing; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D010865:Pilot Projects; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
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; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine