title: Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93.
abstract: OBJECTIVE
  To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity.
  
  
  METHODS
  A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) 87.
  
  
  RESULTS
  Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P =.01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P =.007; and 44% v 31%, P =.01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM.
  
  
  CONCLUSIONS
  Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.
authors.affiliation: Department of Pediatric Hematology/Oncology, University Children's Hospital, Münster, Germany. ucreutzig@aol.com
authors.forename: U
authors.initials: U
authors.lastname: Creutzig
authors.forename: J
authors.initials: J
authors.lastname: Ritter
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.forename: D
authors.initials: D
authors.lastname: Reinhardt
authors.forename: J
authors.initials: J
authors.lastname: Hermann
authors.forename: F
authors.initials: F
authors.lastname: Berthold
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: H
authors.initials: H
authors.lastname: Jürgens
authors.forename: H
authors.initials: H
authors.lastname: Kabisch
authors.forename: W
authors.initials: W
authors.lastname: Havers
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: U
authors.initials: U
authors.lastname: Kluba
authors.forename: F
authors.initials: F
authors.lastname: Niggli
authors.forename: H
authors.initials: H
authors.lastname: Gadner
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use*; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D008942:Mitoxantrone; D015255:Idarubicin; D003630:Daunorubicin