The Experience in Treating Elders with AML Using High-Dose AraC.

Introduction

Cytarabine combined with an anthracycline has long been the basis of therapy for acute myeloid leukemia (AML). Complete remission (CR) with standard therapy in patients > 60 has been reported to be 30 - 50%. Studies to improve remission rates have suggested that induction treatment using high-dose cytarabine (HDAraC) in adults age < 60 is safe and may improve survival in some patients. The use of such an aggressive induction regimen in older (>60) patients has not been extensively studied. The objective of this study was to assess tolerability and efficacy of HDAraC in patients 60 years of age or older compared to those age < 60.

Methods

Chart review of all patients that received induction chemotherapy with HDAraC between 2007 and 2013 at University of Louisville was done evaluating for: disease status and performance status at time of diagnosis, adverse effects during induction treatment, and treatment outcomes. HDAraC treatment in patients > 50 involved cytarabine at 1.5 g/m² every 12 hours for 12 doses; for patients < 50, the cytarabine dose was 3g/m² every 12 hours for 12 doses. Cytarabine was combined with 3 daily doses of idarubicin (12 mg/m²) on days 2-4 in all patients. Response was assessed with bone marrow biopsy on day 30 of induction or until neutropenia resolved.

Results

Seventy-seven patients received HDAraC between 2007 and 2013 (42 patients age < 60 and 35 patients age > 60. One patient < 60 and 8 patients > 60 died before day 30 without remission; 35 (83%) patients < 60 achieved CR and 21 (60%) of patients > 60 achieved CR (p=0.038). Adverse events related to induction chemotherapy were statistically significant more common in patients > 60 for respiratory failure (p=0.01), septic shock (p=0.004), bleeding complications (p=0.029), and cardiac toxicity (p=0.001), but not for kidney failure (p=0.302), gastrointestinal complications (p=0.226), neurotoxicity (p=0.105), or neutropenic fever (p=0.205). Overall toxicities, especially death within 30 days, was increased in patients > 60.

Conclusions

HDAraC induction in patients > 60 had a favorable CR rate (60%) compared to reported CR with conventional therapy, but with more toxicity when compared to younger patients. Additional studies involving a larger study group and subset analysis of cytogenetic and molecular markers could identify a specific elder population that may benefit from high-dose treatment. Evaluation of tools like the Comprehensive Geriatric Assessment (CGA) or a modified HCT-CI in this setting are recommended.