Dose-Intense Etoposide and Cyclophosphamide without Stem Cell Transplantation for the Treatment of Primary Refractory and Relapsed Acute Myeloid Leukemia

34 consecutive patients with PIF or Rel-AML treated with dose-intense EC between 10/2004-12/2011 were evaluated. All patients received initial induction therapy with daunorubicin 45–90mg/m2 IV bolus d1–3 and cytarabine 100mg/m2 CI d1–7, and consolidation with HIDAC for 1–3 courses if CR was achieved. Treatment: 27 patients (79%) received etoposide 3gm/m2 by continuous infusion over 48–72hours followed by cyclophosphamide 50mg/kg iv infusion daily for 3 or 4 days. The remaining 7 patients received reduced etoposide 1.8–2.4gm/m2. The decision to use a given dose of EC was left to the discretion of the treating physician. Chi-Square, Fischers Exact Test and Cox regression analysis were bused for statistical analysis.Patient demographics can be seen in Table 1. Most patients had rel-AML (62%), previous exposure to high or intermediate-dose cytarabine (75%), were < 60 years old (70%), had intermediate or unfavorable cytogenetics (92%), and received at least 1 salvage regimen (in addition to induction and consolidation) prior to dose-intense EC (65%). Patient outcomes are seen in Table 2. Overall, CR was achieved in 32% of patients. Median duration of CR after DI-EC treatment was 5 months. Figure 1 shows overall survival curve. No significant difference in response was found for patient's age >60years (p<0.3085), gender (p<0.1345), exposure to high or intermediate dose cytarabine (p<0.4254), the number of salvage regimens received prior to EP (p<0.1672), or etoposide dose intensity (p<0.5172). Rel-AML patients had significantly higher CR rates compared to PIF (p<0.0145). Subset analysis shows unfavorable karyotype (Figure 2) to be associated with a poorer response (p<0.0223). Grade 3–4 GI toxicity was observed in 19(59%) patients, which was not associated with etoposide dose level (p<0.99) Microbiologically confirmed infections occurred in 26(76%) patients but was not associated with etoposide dose. Treatment related mortality was observed in 6(18%) patients.Dose intense EP therapy was moderately effective in achieving CR, especially in heavily pre-treated rel-AML patients. The regimen was successful as a temporizing treatment prior to allogeneic HSCT. Infection rates are high and warrant close surveillance and early aggressive antibiotic therapy.No relevant conflicts of interest to declare.