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Treatment of Acute Myelogenous Leukemia

Treatment of Acute Myelogenous Leukemia

There have been significant advances in our
understanding of the biology of acute myelogenous leukemia (AML), and to a
lesser extent, in its treatment. Dr. Estey has provided an excellent overview of
the current state of the clinical management of the disease. He has described
both the standard therapeutic approaches, including allogeneic hematopoietic
stem cell transplantation, as well as the role of investigational therapy. The
present state of clinical research in AML is reviewed in some detail in the
context of the broad clinical investigation of the disease at the M. D. Anderson
Cancer Center. Dr. Estey makes a strong argument for the early consideration of
investigational therapy, focusing on patients for whom "standard"
therapy is demonstrably inadequate.

Cytogenetics at Presentation

Several points raised by Dr. Estey regarding clinical practice deserve
particular emphasis. The first is that cytogenetics must be routinely performed
at presentation of AML. It is clear that the prognosis of the disease correlates
closely with the cytogenetics,[1,2] and importantly, the karyotype can have a
profound effect on the choice of treatment (particularly in consolidation). For
example, patients with the more favorable t(8;21) karyotype derive substantial
benefit from consolidation with repeated cycles of high-dose cytarabine, and a
substantial proportion may even be cured with such an approach.[3] How much
"high-dose" cytarabine is actually required, however, remains an open
question.

It is also clear that AML with a complex karyotype, or with -5/-7 monosomies,
has a poor prognosis regardless of therapy, thereby justifying early
consideration of investigational therapy. Moreover, the cytogenetics should also
be confirmed again at relapse because they are important in determining the
prognosis following salvage therapy,[4] and changes in karyotype (usually the
acquisition of an adverse karyotype) are commonly noted.

Flow Cytometry and Documentation of CR

Baseline flow cytometry should also be performed. Although less helpful in
determining prognosis,[5] immunophenotype is sometimes helpful in establishing
the diagnosis (particularly for undifferentiated AML). In addition, it may be
important clinically to note the expression of CD33, the target antigen for
gemtuzumab ozogamicin (Mylotarg).[6] Immunophenotypic changes have been
frequently noted at relapse, and therefore, flow cytometry should again be
performed at that time.[7]

Finally, Dr. Estey appropriately emphasizes the importance of achieving and
documenting complete remission (CR). Patients who achieve CR only after repeated
courses of therapy have a significantly worse outcome[8] and may be candidates
for novel treatment strategies. Therefore, in addition to the demonstration of
an adequately hypocellular (and leukemia-free) bone marrow following treatment,
CR should be documented separately at the time of recovery following induction
chemotherapy.[9]

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