Managing minimal residual malignant disease

So-called complete remission of acute leukemia and other tumors frequently leaves minimal residual disease cells, sometimes causing an inflammatory response and often relapse. Although the remaining cells often have long generation times or may even be in G0 condition, they may form a new tumor mass. This can be explained by cell kinetics alone, or by an escape from immunologic or other control mechanisms, or by a new promoting event. Maintenance chemotherapy beyond the first 6 months seemed only to have an effect where induction chemotherapy was weak and palliative, but not since it has become intensive and sometimes curative: it only increases the relapse incubation time, not the survival. Relapse cells may be refractory to cytostatics previously not given, in part because of alternative metabolic pathways or enzyme induction, in part because of tumor cell progression, and any chemotherapy seems to be able to play a significant role in this progression. The result is a relatively high residual tumor mass and a short duration of rare second remissions. Adjuvant immunotherapy, despite controversies about its results, seems to work in some tumors, but the statistical methods applied and the monitoring have been criticized. The strategy proposed for potentially 'curable' tumors (leukemias, lymphomas, embryomas) with short cell generation times is therefore intensive remission induction aiming at the smallest possible residual disease cell number. It is conceivable that this induction might mean accepting risks comparable to those accepted for transplant patients. Manipulation of the bioimmunological response can be effective even against cells in the G0 phase. New methods are proposed to manage residual disease of solid tumors with long generation times, and only maintenance chemotherapy active on cells with a long generation time is suggested.