Treatment of acute myeloid leukemia: state-of-the-art and future directions.
Despite major recent advances in the understanding of the molecular biology of the disease, the treatment of acute myeloid leukemia (AML) in adults remains challenging. For the 75% of AML patients older than 60 years, currently available treatments produce significant toxicity with poor overall response rates and survival. In younger patients, standard regimens using cytarabine and an anthracycline for induction followed by some form of intensive postremission therapy can produce response rates of 70% with 5-year relapse-free survival rates of 25% to 40%. Chromosomal analyses define three prognostic categories with favorable, intermediate, and unfavorable risk. In older adults, AML appears to be an intrinsically resistant disorder of proximal pluripotent hematopoietic stem cells. A variety of targeted therapies currently in development include modulators of MDR1-mediated drug resistance, immunotherapeutics, angiogenesis inhibitors, proapoptotic antisense oligonucleotides, and specific small molecule inhibitors of tyrosine kinase and farnesyltransferase. For example, oral farnesyltransferase inhibitors have demonstrated activity and tolerability in patients with refractory AML and are now in phase II testing. Such targeted therapeutics offer the promise of novel antileukemic activity combined with an improved therapeutic index.
Stone
Richard M
RM
Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D007167:Immunotherapy; D007951:Leukemia, Myeloid / Q000628:therapy*; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy
D000970:Antineoplastic Agents