Acute Myeloid Leukemia (AML): The Role of Intensive Induction Chemotherapy

Abstract

Intensive induction therapy-in acute myeloid leukemia (AML), as in some other systemic malignancies- is a strategy fundamentally different from post-remission strategies. Approaches like consolidation treatment, prolonged mainte¬nance, and autologous or allogeneic transplantation in the first remission are directed against minimal residual disease with a malignant cell population having survived the induction treatment. In contrast, induction therapy deals with naive tumor cells possibly different in their sensitivity from their counterparts in remission. Therefore, in AML it has been suggested to introduce intensification strategies into the induction part of treatment as a new step after the preceding intensification steps in the post-remission part. As expected from the dose effects observed in post-remission treatment using more AraC or longer treatment, similar dose effects have been found in the induction treatment both by the incorporation of high-dose AraC and by the double induction strategy administered in patients up to 60 years of age. For example, patients with poor risk AML due to an unfavorable karyotype, high LDH in serum, or delayed response, benefited from double induction containing high-dose AraC by a longer survival as compared to that from standard dose AraC. A corresponding dose effect in the induction treatment has been found in patients of 60 years and older receiving daunorubicin 60 vs 30 mg/m2 as part of the TAD regimen with higher dosage. This treatment significantly increased the response and survival rate in older patients who represented a poor risk group as a whole. Thus, we could demonstrate, both in younger and older patients, that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits a cumulative toxicity in that a repetition of courses containing high-dose AraC in the post-remission period is associated with considerable myelotoxicity leading to longlasting aplasias of about 6 weeks. However, after intensive induction treatment, high-dose chemotherapy in remission may become practicable using autologous stem cell rescue and may contribute to a further improvement of the outcome in poor risk as well as average patients with AML. These approaches are currently investigated by the German AMLCG. While there are clear limitations in the intensity of antineoplastic treatment for AML, as for other systemic malignancies, some further intensification may be possible and effective.

Keywords

• double induction
• high-dose AraC
• daunorubicin dosage