Improvement in pediatric acute myelogenous leukemia (AML) over the past 30 years has been only modest. Although rates of complete remission induction have climbed steadily to 85% or 90%, cure rates remain in the 50% to 60% range. These figures may inspire envy from medical oncologists treating adults with AML, but they lag far behind the successes in treating pediatric acute lymphocytic leukemia (ALL).
In their review of the modern therapy experience in pediatric AML, Drs. Loeb and Arceci have done an admirable job in providing a comprehensive synthesis of the therapeutic experience to date. They summarize the extensive experience of the most important single and multicenter trials, including those of the American, British, Scandinavian, and other European groups, and arrive at several general conclusions.
First, the known active agents—cytarabine, the anthracyclines, etoposide, and the alkylating agents—appear to generate optimal results when applied in both dose- and schedule-intensive strategies during the first several months of therapy. Second, short, intensive therapies (ie, 1 to 2 years) are adequate to cure many patients, whereas prolonged therapies (intensive or not) appear only to add to toxicity without a corresponding improvement in efficacy.
Third, with the notable exception of the Medical Research Council’s MRC AML10 trial, allogeneic bone marrow transplantation has been shown to be more effective than chemotherapy alone, but outcomes after autologous transplantation have generally been found to be the same or worse than those with chemotherapy alone. The emerging role of biological and cytogenetic features in defining different prognostic groups is also highlighted.
In their discussion of new therapies, the authors outline the promise attendant to several newer approaches being studied. These include differentiation induction with retinoids and arsenic trioxide (Trisenox), in both acute promyelocytic (APL) and other FAB subgroups; inhibition of DNA methylation and acetylation and of tyrosine kinase; and several immune-based strategies using exogenous antibodies, tumor vaccines, or cytokine-treated AML blasts as antigen-presenting dendritic cells.
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