Patients with the most common form of leukaemia (acute myeloid leukaemia) receive ten times more chemotherapy than necessary. This was revealed by a team of Dutch hematologists. 'It is expected that this finding will lead to worldwide adjustments in the doses so that patients will experience less side-effects' says Dr Bob Löwenberg, Professor of Hematology at the Erasmus University Medical Center in Rotterdam, The Netherlands. These recent developments are presented at the 16th Congress of the European Hematology Association in London.

Acute Myeloid Leukemia (AML) is a cancer of blood cells. The standard chemotherapeutic approach in AML is based on the use of anthracyclines and cytarabine. This globally accepted combination of drugs nowadays achieves cure in about 40% of adults with AML in the age range up to 60 years.

"Our recent study has revisited the dose level of cytarabine, one of these cornerstone drugs, and demonstrated in a large prospective randomised multicenter trial that a commonly used high-dose levels of cytarabine (in the range of 2000 -3000 mg/m2 twice daily) are not necessary", says Dr Löwenberg.

These high doses appear to be above the plateau of the dose-response relationship. In a direct comparison a schedule with cytarabine at 1000 mg/m2 showed equivalent results in terms of response- and relapse rates as well as survival but with reduced toxicities.

This apparent significant reduction in toxicity resulted in shorter hospital stay and a reduced requirement for platelet transfusions. Thus the classical high-dose of cytarabine may represent an unnecessary overdose of this important cytostatic agent that also compromises subsequent treatment and the introduction of additional active drugs to the standard combination. These insights are likely to have an impact upon the standard of care of acute myeloid leukaemia.

New developments in molecular diagnosis

Efforts continue to identify genomic alterations that have a role in the development of leukaemia and have value in increasing our understanding of the clinical features of the disease. Dr Löwenberg: "The recent explosion of newly discovered abnormalities also appears useful for improving the accuracy and precision of diagnosis. Genomic technologies allowing for a genome wide analysis have led the way towards the detection of entirely new categories of abnormalities. Successively, two important new gene mutations were identified, ie mutations in the genes of IDH1 and IDH2 (isocitrate dehydrogenases 1 and 2) and DNMT3A (DNA methyltransferase 3A). These gene mutations appear to be notably common in acute myeloid leukemia. The latter gene mutations are present in as many as 20%-30% of cases of acute myeloid leukemia. The mutation in the gene DNMT3A, has a role in gene regulation or epigenetics.

Epigenetic abnormalities during the last year have been shown to follow characteristic and highly specific patterns. These discoveries are likely to offer leads in the development of novel drugs that may interfere with these altered pathways with profound effects on cellular growth."

Source: European Hematology Association