title: Gemtuzumab Ozogamicin Reduces Relapse Risk in FLT3/ITD Acute Myeloid Leukemia: A Report from the Children's Oncology Group.
abstract: OBJECTIVE
  Gemtuzumab ozogamicin (GO), a calicheamicin-conjugated mAb against CD33, has been used in the treatment of acute myeloid leukemia (AML). We evaluated the impact of the addition of GO to standard chemotherapy and hematopoietic stem cell transplant (HCT) in patients withFLT3/ITD.
  
  
  METHODS
  We analyzed children withFLT3/ITD-positive AML (n= 183) treated on two consecutive Children's Oncology Group AML trials (NCT00070174andNCT00372593). Outcomes were assessed forFLT3/ITD patients receiving standard chemotherapy with or without GO (GO vs. No-GO, respectively), and the impact of consolidation HCT for high-riskFLT3/ITD patients [highFLT3/ITD allelic ratio (ITD-AR)].
  
  
  RESULTS
  For allFLT3/ITD patients, complete remission (CR) rates for the GO versus No-GO cohorts were identical (64% vs. 64%;P= 0.98). Relapse rate (RR) after initial CR was 37% for GO recipients versus 59% for No-GO recipients (P= 0.02), disease-free survival (DFS) was similar (47% vs. 41%;P= 0.45), with higher treatment-related mortality (TRM) in GO recipients (16% vs. 0%;P= 0.008). Among high-riskFLT3/ITD patients with high ITD-AR, those who received HCT in first CR with prior exposure to GO had a significant reduction in RR (15% vs. 53%;P= 0.007), with a corresponding DFS of 65% versus 40% (P= 0.08), and higher TRM (19% vs. 7%;P= 0.08).
  
  
  CONCLUSIONS
  CD33 targeting with HCT consolidation may be an important therapeutic strategy in high-riskFLT3/ITD AML and its efficacy and associated toxicity warrant further investigation.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington. ktarlock@fredhutch.org.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tarlock
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.affiliation: Department of Statistics, Children's Oncology Group, Monrovia, California.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.affiliation: Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Betsy A
authors.initials: BA
authors.lastname: Hirsch
authors.affiliation: Division of Haematology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
authors.affiliation: Maine Children's Cancer Program, Maine Medical Center, Scarborough, Maine.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Pollard
authors.affiliation: Pediatric Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
authors.affiliation: Hematologics Incorporated, Seattle, Washington.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loken
authors.affiliation: Hematology/Oncology, Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Gamis
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D000079982:Gemtuzumab; D020440:Gene Duplication; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000079982:Gemtuzumab; D051941:fms-Like Tyrosine Kinase 3