title: Mitoxantrone and cytarabine induction, high-dose cytarabine, and etoposide intensification for pediatric patients with relapsed or refractory acute myeloid leukemia: Children's Cancer Group Study 2951.
abstract: OBJECTIVE
  To evaluate the response rate, survival, and toxicity of mitoxantrone and cytarabine induction, high-dose cytarabine and etoposide intensification, and further consolidation/maintenance therapies, including bone marrow transplantation, in children with relapsed, refractory, or secondary acute myeloid leukemia (AML). To evaluate response to 2-chlorodeoxyadenosine (2-CDA) and etoposide (VP-16) in patients who did not respond to mitoxantrone and cytarabine.
  
  
  METHODS
  Patients with relapsed/refractory AML (n = 101) and secondary AML (n = 13) were entered.
  
  
  RESULTS
  Mitoxantrone and cytarabine induction achieved a remission rate of 76% for relapsed/refractory patients and 77% for patients with secondary AML, with a 3% induction mortality rate. Cytarabine and etoposide intensification exceeded the acceptable toxic death rate of 10%. The response rate of 2-CDA/VP-16 was 8%. Two-year overall survival was estimated at 24% and was better than historical control data. Patients with secondary AML had similar outcomes to relapsed or refractory patients. Initial remission longer than 1 year was the most important prognostic factor for patients with primary AML (2-year survival rate, 75%), whereas for patients with primary AML, with less than 12 months of initial remission, survival was 13% and was similar to that of refractory patients (6%).
  
  
  CONCLUSIONS
  Mitoxantrone and cytarabine induction is effective with reasonable toxicity in patients with relapsed/refractory or secondary AML. The cytarabine and etoposide intensification regimen should be abandoned because of toxicity. Patients with relapsed AML with initial remissions longer than 1 year have a relatively good prognosis.
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA. rjwells@mdanderson.org.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wells
authors.forename: Mary T
authors.initials: MT
authors.lastname: Adams
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Jonathan
authors.initials: J
authors.lastname: Buckley
authors.forename: Allen B
authors.initials: AB
authors.lastname: Buxton
authors.forename: Kathryn
authors.initials: K
authors.lastname: Dusenbery
authors.forename: Alan
authors.initials: A
authors.lastname: Gamis
authors.forename: Margaret
authors.initials: M
authors.lastname: Masterson
authors.forename: Terry
authors.initials: T
authors.lastname: Vik
authors.forename: Phyllis
authors.initials: P
authors.lastname: Warkentin
authors.forename: James A
authors.initials: JA
authors.lastname: Whitlock
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone