Survival improvement over time of 960 s-AML patients included in 13 EORTC-GIMEMA-HOVON trials

Abstract

We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p < 0.001): 7.7% (95% CI: 1.3–21.7%) for patients treated before 1990 (period 1: n = 26), 23.3% (95% CI: 17.1–30.0%) for those treated between 1990 and 2000 (period 2: n = 188) and 36.5% (95% CI: 28.7– 44.3%) for those treated in 2000 or later (period 3: n = 153). In multivariate analysis, male gender (HR = 1.39; p = 0.01), WBC ≥ 25 × 109/L (HR = 2.00; p < 0.0001), age 46-60 years (HR = 1.65; p < 0.001) and poor-risk cytogenetics (HR = 2.17; p < 0.0001) were independently associated with shorter OS, while being treated during period 2 (HR = 0.50, p = 0.003) or period 3 (HR = 0.43; p = 0.0008). Having received high-dose cytarabine (HD-AraC) (n = 48) in the induction chemotherapy (HR = 0.54, p = 0.012) was associated with a longer OS. In contrast, among patients >60 years of age (n = 502), the OS was dismal, and there was no improvement over time.