Time To Complete Remission Is Not a Significant Prognostic Factor in AML: A Report on 1,959 Consecutive Patients Registered to 6 Studies of the Eastern Cooperative Oncology Group (ECOG).

Abstract

Prognostic factors for AML at diagnosis include cytogenetics, FLT3 ITD, age, MDR status and white cell count at presentation. Several groups (Blood 2000; 95:72; BJH 1999; 107:69; Haematologica 2004; 89:528) have reported that time to achievement of complete remission (CR) is an independent post-induction prognostic factor in AML. Furthermore, some investigators have classified patients who do not achieve CR with one cycle as primary induction failure. Between 1983 and 1993 1,959 patients were registered to 6 consecutive ECOG studies (E3483, PC486, E1490, E2491/INT0129, E3489 and E3993). These studies were for patients age 18–55 years (E3483, PC486 and E3489); age 56–70 years (E1490); age >56 years (E3993) and with no age limit (E2491/ INT0129). Of these 1,959 patients, 1261 achieved CR (64%) and were available for analysis. All patients received standard induction therapy, consisting of daunorubicin 60 mg/m2 (E3483, PC486 and E1490), or 45 mg/m2 (E2491/ INT0129) or idarubicin 12 mg/m2 (E3489), or a randomization between daunorubicin 45 mg/m2, idarubicin 12 mg/m2 or mitoxantrone 12 mg/m2 (E3993) - all for 3 days - together with cytarabine 100–200 mg/m2 by continuous infusion for 7 days. It should be noted that in the North American Intergroup APL study (E2491/ INT0129) patients who received ATRA in induction are excluded from this analysis. All patients were to receive a second cycle of identical induction therapy if the day 10–14 bone marrow demonstrated unequivocal residual leukemia. Identical study-specific post-remission therapy, including consolidation therapy and/or allogeneic or autologous bone marrow transplantation, was given to all patients who went into CR - irrespective if this was achieved after 1 or 2 cycles. This retrospective analysis compared patients who achieved CR after 1 cycle versus 2 cycles of induction therapy. The data were obtained from the ECOG database that recorded the number of days that patients received induction therapy (≤8 days vs >8 days). The table presents the data for disease-free survival (DFS) and overall survival (OS). These data are based on the Cox model, adjusting for other variables.TotalFailedMedian DFS/OS (mo)5-year DFS/OSp-valueDFS1 cycle40632110.224.4%2 cycles85562911.928.6%0.07OS1 cycle40628723.736.1%2 cycles85558324.135.7%0.7In this large cohort of patients, by multivariate analysis, age, WBC at diagnosis were significant factors for DFS and OS. However, the number of cycles given for induction or the time to achieve a CR in AML patients could not be demonstrated to have any independent prognostic significance. These data suggest that post-remission strategies in AML should not be influenced by the number of cycles required to achieve CR.