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(Drug information on cytarabine), and a substantial proportion may even be cured with such an approach. 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, 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, 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). Immunophenotypic changes have been frequently noted at relapse, and therefore, flow cytometry should again be performed at that time.
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 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.