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Treatment of Acute Myelogenous Leukemia

Treatment of Acute Myelogenous Leukemia

Therapeutic strategies are evolving for the treatment
of patients with newly diagnosed acute myelogenous leukemia (AML), as well as
for those with relapsed or refractory disease. Clinical and laboratory studies
have demonstrated that AML is not a single disease, but a heterogeneous group of
diseases with different clinical features and natural histories. There are
variable responses to therapy depending on both the biologic characteristics of
the disease and the clinical characteristics of the patient. Nevertheless,
studies evaluating the outcomes of relatively large numbers of patients with
newly diagnosed AML show that the majority still die of their disease.[1-3]

Older adults with AML fare particularly poorly.[1-3] However, patients with
several subtypes identified by specific cytogenetic abnormalities, including
inv(16) or t(16;16); t(8;21); or t(15;17), have a much more favorable outcome
with contemporary strategies.[4-11] Although much progress has been made in the
treatment of AML patients with favorable karyotypes, the lack of progress in
both older adults and those with unfavorable karyotypes has been disappointing.
These cohorts of patients represent the major challenge for the future.

Dr. Estey, in his concise and comprehensive article, has provided us with the
armamentarium to meet these challenges. His most important message focuses on
the identification of patients with less than favorable prognoses and the
importance of their enrollment into clinical trials that rationally test novel
antileukemic agents and therapeutic strategies. Many of these new agents are
based on the discovery of new molecular and immunophenotypic targets. The number
of new agents available to explore is impressive.

New Agents and New Targets for AML

The anti-CD33 calicheamicin immunoconjugate, gemtuzumab ozogamicin (Mylotarg),
is the first of these new targeted agents approved by the US Food and Drug
Administration for clinical use in AML.[12] The overall remission rate is 30%,
which includes complete remissions by standard definitions plus complete
remissions by all criteria with the exception of incomplete platelet recovery.
Although similar remission rates can be achieved in patients in first relapse
using a variety of other chemotherapy regimens (including high-dose cytarabine
[ara-C]),[13] gemtuzumab ozogamicin represents novel technology: an antibody
linked to a potent cytotoxic agent that can be administered on an outpatient
basis. Furthermore, it appears that this agent is effective not only in patients
with favorable prognostic karyotypes, but also in those with intermediate- or
poor-prognosis cytogenetics.[12]

A second new class of agents is the farnesyl transferase inhibitors,[14]
which have shown encouraging results in a preliminary trial.[15] Dr. Estey
raises the exciting possibility that the bcr-abl tyrosine kinase inhibitor
imatinib mesylate (STI571, Gleevec), which is so effective in patients with
chronic myeloid leukemia,[16] may also play a role in patients with AML because
of its ability to inhibit the tyrosine kinase associated with c-kit.[17,18]

Overview of Prognostic Factors

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