Treatment of relapsed acute myeloid leukaemia

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia among adults with an incidence that increases with age. Modern induction chemotherapy will result in complete remission in 50-90% of patients with de novo disease, but between 10 and 25% of patients will have primary refractory disease and the majority of those who gain remission will relapse within 3 years of diagnosis. Treatment of relapsed leukaemia is difficult and well-controlled trials in this group of patients are uncommon. Usually, patients are recruited to relatively small phase I and phase II trials examining the potential role for new drug approaches and many combination regimens based around high doses of cytarabine arabinoside, substitution of the anthracyclines mitoxantrone or idarubicin for daunorubicin or using amsacrine have become established. However, these trials are generally unrandomised and produce second CR rates of 10-70% relying on historical controls. This article reviews the results of published randomised trials in relapse and refractory AML. Questions addressed include the role of high dose cytarabine, with or without the addition of etoposide or mitoxantrone, the use of timed sequential chemotherapy regimens, and growth factors as a means to increase leukaemia cell sensitivity and interference with drug resistance proteins.