Remission induction therapy: the more intensive the better?

Intensive induction therapy in acute myeloid leukemia (AML) as in some othe r systemic malignancies is a strategy fundamentally different from post-rem ission strategies. Approaches such as consolidation treatment, prolonged ma intenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to sp ecial genetic or kinetic features. In contrast, induction therapy deals wit h naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the in troduction of intensification strategies into the induction phase of treatm ent has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-rem ission treatment with high-dose cytarabine (AraC) or longer treatment, simi lar dose effects have been found in induction treatment both from the incor poration of high-dose AraC and from the double-induction strategy used in p atients tip to 60 years of age. As a particular effect, patients with poor- risk AML according to an unfavorable karyotype, high LDH in serum, or a del ayed response show longer survival following double induction containing hi gh-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been fo und with daunorubicin 60 vs 30 mg/m(2) as part of the thioguanine/AraC/daun orubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-ris k group as a whole. Thus we have been able to demonstrate both in younger a nd older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulati ve toxicity in that repeated courses containing high-dose AraC in the post- remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvem ent in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooper ative Group (AMLCG). "The more intensive the better" is certainly not the w ay to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.