Patients with acute myeloid leukemia (AML), a cancer of the blood and bone marrow which is also called acute myelogenous leukemia or acute myeloblastic leukemia, receive ten times more chemotherapy than necessary. This was revealed by a team of Dutch hematologists at the 16th Congress of the European Hematology Association in London.

Commenting on these findings,Bob L?wenberg, Professor of Hematology at the Erasmus University Medical Center in Rotterdam, The Netherlands said: “It is expected that this finding will lead to worldwide adjustments in the doses so that patients will experience less side-effects.”

In patients with Acute Myeloid Leukemia (AML) myeloid stem cells usually develop into a type of immature white blood cell called myeloblasts. These myeloblasts are abnormal and do not become healthy white blood cells. In Acute Myeloid Leukemia too many stem cells can also develop into abnormal red blood cells or platelets. These abnormal white blood cells, red blood cells, or platelets are also called leukemia cells or blasts. These leukemia cells may build up in the bone marrow and blood, leaving less room for healthy white blood cells, red blood cells, and platelets. As a result, infection, anemia, or easy bleeding may occur.

Standard therapy
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 randomized multicenter trial that a commonly used high-dose levels of cytarabine (in the range of 2000 -3000 mg/m2 twice daily) are not necessary?, L?wenberg explained.

Dose-response relationship
These high doses appear to be above the plateau of the dose-response relationship. In a direct comparison a schedule with cytarabine at 1,000 mg/m2 showed equivalent results in terms of response- and relapse rates as well as survival but with reduced toxicities.

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This apparent significant reduction in toxicity resulted in shorter hospital stay and a reduction in 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 leukemia.

Molecular diagnosis
Efforts continue to identify genomic alterations that have a role in the development of leukemia and have value in increasing our understanding of the clinical features of the disease. Notes L?wenberg: ?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.?

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