title: Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16).
abstract: Patients with core binding factor acute myeloid leukemia (CBF-AML) benefit from more intensive chemotherapy, but whether both the t(8;21) and inv(16)/t (16;16) subtypes requires intensification remained to be determined. In the 2 successive studies (AML-BFM-1998 and AML-BFM-2004), 220 CBF-AML patients were treated using the same chemotherapy backbone, whereby reinduction with high-dose cytarabine and mitoxantrone (HAM) was scheduled for these cohorts only in study AML-BFM-1998 but not in AML-BFM-2004 against the background to minimize overtreatment. Five-year overall survival (OS) and event-free survival (EFS) were significantly higher and the cumulative incidence of relapse (CIR) lower in t(8;21) patients treated with HAM (n = 78) compared with without HAM (n = 53): OS 92% ± 3% versus 80% ± 6%, p(logrank)0.047, EFS 84% ± 4% versus 59% ± 7%, p(logrank)0.001, and CIR 14% ± 4% versus 34% ± 7%, p((gray))0.006. These differences were not seen for inv(16) (n = 43 and 46, respectively): OS 93% ± 4% versus 94% ± 4%, EFS 75% ± 7% versus 71% ± 9% and CIR 15% ± 6% versus 23% ± 8% (not significant). The subtype t(8;21), but not inv(16), was an independent predictor of worse outcome without HAM reinduction. Based on our data, a 5-year OS of > 90% can be expected for CBF-AML, when stratifying t(8;21), but not inv(16), patients to high-risk chemotherapy, including HAM reinduction.
authors.affiliation: Pediatric Hematology/Oncology, University Hospital Muenster, Muenster, Germany;
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bourquin
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dworzak
authors.forename: Christine
authors.initials: C
authors.lastname: von Neuhoff
authors.forename: Annette
authors.initials: A
authors.lastname: Sander
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Andrea
authors.initials: A
authors.lastname: Teigler-Schlegel
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Selim
authors.initials: S
authors.lastname: Corbacioglu
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002648:Child; D007446:Chromosome Inversion / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050660:Core Binding Factors / Q000235:genetics; D003561:Cytarabine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D012008:Recurrence; D014178:Translocation, Genetic / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D050660:Core Binding Factors; D003561:Cytarabine; D008942:Mitoxantrone