Chronic myeloid leukemia: standard treatment options.
OBJECTIVE
Treatment options for chronic myeloid leukemia (CML) are discussed.


CONCLUSIONS
In the 1980s busulfan and hydroxyurea were the standards of care. These were subsequently replaced by interferon alpha (IFN alpha) based therapy. Currently, bone marrow transplant survival has improved, making this also a viable option. Five-year progression-free survival averaged above 70% for chemotherapeutic options. Transplant survival at 56 months was approximately 60%; however, these survivors were generally cured of disease. The recognition of the role for BCR-ABL in CML has led to the development of specific kinase inhibitors such as imatinib. Clinical trial evidence has demonstrated a clear superiority of imatinib over interferon plus cytarabine, making this the new standard of care in first-line treatment of CML. Resistance to imatinib has been observed, in addition to relapse. The data suggest that the probability of response may be estimated as early as six months after initiation of imatinib therapy. Although combinations of imatinib with IFN alpha show small improvements compared to imatinib therapy alone, the biggest improvements were seen when imatinib doses were doubled. Unfortunately, not all patients can tolerate this increase in dose. The most common mechanism for imatinib resistance is the presence of a mutated BCR-ABL kinase. Several of these mutants have been cloned and characterized.


CONCLUSIONS
Molecular-targeted BCR-ABL kinase inhibitors, such as imatinib, are now first-line treatment for CML. Allogeneic stem cell transplant is still the only proven curable treatment for CML in patients with an appropriate donor. Next generation BCR-ABL kinase inhibitors hold promise for patients with mutated BCR-ABL kinase that confer resistance to imatinib.
Frame
David
D
University of Michigan Hospital, Department of Pharmacy UHB2D301, Ann Arbor, MI 48109, USA. dframe@med.umich.edu
D004358:Drug Therapy / Q000379:methods* / Q000639:trends; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D016019:Survival Analysis
D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors; D006918:Hydroxyurea