Therapy of Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults1. Over the past twenty years, the studies on the pathogenesis and prognosis of AML have made considerable progress. Clinically, patients with AML typically present with signs or symptoms of bone marrow failure, although sometimes they can present with symptoms of leukostasis with pulmonary or neurological dysfunction. Rarely, patients will present with primary extramedullary disease, which should be approached in the same way as systemic AML. A certain number of factors can be involved in the etiology of AML: as an example, exposure to ionizing radiation and long-term exposure to benzene are known risk factors. AML could be part of the natural history of patients with congenital disorders of DNA repair, such as the Fanconi's anemias; also the myeloproliferative disorders (MPD) and myelodysplastic syndromes (MDS). AML is a heterogeneous disease; standard treatments may be applied to biologically distinct subgroups, resulting in different treatment outcomes. However, less than one-third of all adult patients with AML can be cured even to this date. The treatment of refractory, relapsed and elderly AML remains a major challenge. In recent years, new regimens and novel agents are being studied in an effort to improve complete remission (CR) rate and overall survival. The concept of risk-adapted therapy allows for recognition of this biologic diversity by incorporating key biologic features, such as cytogenetic and molecular markers, when formulating treatment regimens and investigating emerging targeted therapies based on disease characteristics. Although AML has been the focus of significant laboratory and clinical investigation, it remains difficult to treat, perhaps partly because of the fundamental nature of the disorder, which requires substantial institutional resources to adequately deal with the complications of bone marrow failure and sustain patients through periods of intensive therapy. Several large studies have helped categorize chromosomal abnormalities into good-, intermediate-, and poor-risk groups2-5. This hierarchical system of karyotype classification is predictive value across different age groups in de novo and secondary AML. It was also found to retain prognostic significance across the different treatment modalities of chemotherapy and autologous and allogeneic bone marrow transplantation. Generally, the poor-risk or unfavorable group includes those with complex karyotypes (> 3-5 abnormalities), chromosome 5 or 7 abnormalities, or chromosome 3q abnormalities. The results for these patients are dismal, with standard chemotherapy causing some to advocate