title: [Improved treatment results in children with AML: Results of study AML-BFM 93].
abstract: BACKGROUND
  In the multicenter trial AML-BFM 93 daunorubicin or idarubicin was randomly applied in all patients during induction in combination with cytarabine and etoposide. After induction all patients were stratified to the standard or high risk group. To improve outcome in high risk patients high dose cytarabine and mitoxantrone (HAM) was introduced. The placing of HAM as either the 2nd or 3rd therapy block was randomized to evaluate the efficacy and toxicity accordingly.
  
  
  METHODS
  471 children with de novo AML entered the trial AML-BFM 93 (161 standard risk, 310 high risk).
  
  
  RESULTS
  Overall, 387 of 471 (82 %) patients achieved remission, 5-year survival, event free survival (EFS), and disease free survival were 60 % SE 3 %, 51 % SE 2 % and 62 % SE 3 %, respectively. Idarubicin-based induction resulted in a significantly better blast cell reduction in the bone marrow on day 15 (25 of 144=17 % patients with > 5 % blasts compared to 46 of 149=31 % patients after daunorubicin, pchi(2)=0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19 % vs. 38 %, pchi(2)=0.007). Cardiotoxicity, WHO grade 1 - 3 shortening fraction reduction after induction occurred in 6 % patients in both arms. In the total group of patients probabilities of five years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin. However, in patients presenting with more than 5 % blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (p logrank 0.06). Outcome in high risk patients was superior in study 93 compared to study 87 (remission rate and 5-year pEFS in study AML-BFM 93 vs. study 87: 78 % vs. 68 %, p=0.007, and 44 % vs. 31 %, p logrank=0.01). The placing of HAM as the 2nd or 3rd therapy block was of minor importance. However, patients who received the daunorubicin treatment during induction benefited from early HAM.
  
  
  CONCLUSIONS
  Compared to study AML-BFM 87 treatment results in study AML 93 improved significantly in high risk patients. This can partly be contributed to the better response on day 15 after idarubicin induction but is mainly due to the introduction of HAM.
authors.affiliation: Universitäts-Kinderkliniken in Deutschland, Münster, Germany. ucreutzig@aol.com
authors.forename: U
authors.initials: U
authors.lastname: Creutzig
authors.forename: F
authors.initials: F
authors.lastname: Berthold
authors.forename: J
authors.initials: J
authors.lastname: Boos
authors.forename: G
authors.initials: G
authors.lastname: Fleischhack
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: A
authors.initials: A
authors.lastname: Gnekow
authors.forename: U
authors.initials: U
authors.lastname: Graubner
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: J
authors.initials: J
authors.lastname: Hermann
authors.forename: P
authors.initials: P
authors.lastname: Imbach
authors.forename: H
authors.initials: H
authors.lastname: Jürgens
authors.forename: H
authors.initials: H
authors.lastname: Kabisch
authors.forename: D
authors.initials: D
authors.lastname: Körholz
authors.forename: C M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: D
authors.initials: D
authors.lastname: Reinhardt
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: J
authors.initials: J
authors.lastname: Ritter
authors.forename: H J
authors.initials: HJ
authors.lastname: Spaar
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects*; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects*; D011379:Prognosis; D012074:Remission Induction; D012306:Risk; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone; D015255:Idarubicin; D003630:Daunorubicin
vernacular_title: Verbesserung der Prognose bei Kindern mit AML: Ergebnisse der Studie AML-BFM 931.