Current and emerging therapies for acute myeloid leukemia

Abstract

Background: Acute myeloid leukemia (AML) is a clonal disease characterized by the proliferation and accumulation of myeloid progenitor cells in the bone marrow, which ultimately leads to hematopoietic failure. The incidence of AML increases with age, and older patients typically have worse treatment outcomes than do younger patients.

Objective: This review is focused on current and emerging treatment strategies for nonpromyelocytic AML in patients aged <60 years.

Methods: A literature review was conducted of the PubMed database for articles published in English. Publications from 1990 through March 2009 were scrutinized, and the search was updated on August 26, 2009. The search terms used were: acute myeloid leukemia in conjunction with treatment, chemotherapy, stem cell transplantation, and immunotherapy. Clinical trials including adults with AML aged > or =19 years were selected for analysis. Conference proceedings from the previous 5 years of The American Society of Hematology, The European Hematology Association, and The American Society for Blood and Marrow Transplantation were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Results: Cytarabine (AraC) is the cornerstone of induction therapy and consolidation therapy for AML. A standard form of induction therapy consists of AraC (100-200 mg/m(2)), administered by a continuous infusion for 7 days, combined with an anthracycline, administered intravenously for 3 days. Consolidation therapy comprises treatment with additional courses of intensive chemotherapy after the patient has achieved a complete remission (CR), usually with higher doses of the same drugs as were used during the induction period. High-dose AraC (2-3 g/m(2)) is now a standard consolidation therapy for patients aged <60 years. Despite substantial progress in the treatment of newly diagnosed AML, 20% to 40% of patients do not achieve remission with the standard induction chemotherapy, and 50% to 70% of first CR patients are expected to relapse within 3 years. The optimum strategy at the time of relapse, or for patients with the resistant disease, remains uncertain. Allogeneic stem cell transplantation has been established as the most effective form of antileukemic therapy in patients with AML in first or subsequent remission. New drugs are being evaluated in clinical studies, including immunotoxins, monoclonal antibodies, nucleoside analogues, hypomethylating agents, farnesyltransferase inhibitors, alkylating agents, FMS-like tyrosine kinase 3 inhibitors, and multidrug-resistant modulators. However, determining the success of these treatment strategies ultimately requires well-designed clinical trials, based on stratification of the patient risk, knowledge of the individual disease, and the drug's performance status.

Conclusions: Combinations of AraC and anthracyclines are still the mainstay of induction therapy, and use of high-dose AraC is now a standard consolidation therapy in AML patients aged <60 years. Although several new agents have shown promise in treating AML, it is unlikely that these agents will be curative when administered as monotherapy; it is more likely that they will be used in combination with other new agents or with conventional therapy.