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Keywords:

  • acute myeloid leukaemia;
  • cytarabine;
  • HiDAC;
  • induction chemotherapy

Abstract

Background/Aim

Although induction chemotherapy comprising high-dose cytarabine (HiDAC) in combination with idarubicin and etoposide or ‘ICE’ for adult acute myeloid leukaemia (AML) produces a complete remission rate of nearly 80%, gastrointestinal toxicity is significant. Omission of etoposide may produce similar clinical outcomes with potentially less gastrointestinal toxicity.

Methods

Fifty-three consecutive patients aged 15–60 with newly diagnosed AML, receiving high-dose cytarabine induction at the Alfred Hospital, Melbourne, were retrospectively analysed. Regimens included HiDAC-3 (idarubicin 12 mg/m2 day 1–3, cytarabine 3 gm/m2 bd day 1,3,5,7) or ICE (idarubicin 9 mg/m2 day 1–3, cytarabine 3 g/m2 bd day 1,3,5,7, etoposide 75 mg/m2 day 1–7). Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.03.

Results

Thirty-one patients received HIDAC-3 and 22 patients received ICE induction. HiDAC-3 was better tolerated than ICE in terms of lower frequency of grade 3–4 nausea (0% vs 41%; P < 0.01), grade 3–4 diarrhoea (26% vs 55%; P = 0.05), lower rates of radiologically evident enterocolitis (6% vs 32%; P = 0.03) and less cumulative days of total parenteral nutrition use (1.2 vs 7.3 days; P < 0.01). Times to haematological recovery were similar between the two regimens. Thirty-day mortality was 0% for HiDAC-3 and 9% for ICE. Eighty-four per cent of HiDAC-3-treated patients achieved complete remission after the first cycle of therapy, compared with 77% with ICE. No differences in survival were evident between the two regimens.

Conclusions

HiDAC-3 is a clinically effective induction regimen for adult AML, producing a high rate of first-cycle complete remission with less treatment-related gastrointestinal toxicity than ICE.