Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16)
Abstrakt
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) sub-types 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 over-treatment.
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.