Allogeneic cell-mediated immunotherapy at the stage of minimal residual disease following high-dose chemotherapy supported by autologous stem cell transplantation.
Cumulative clinical experience suggests that immunotherapy may be an effective tool for eradicating tumor cells resistant to maximum tolerated doses of chemotherapy and radiation. Immunotherapy is much more effective when applied at the stage of minimal residual disease, especially against slowly growing tumors because development of graft-versus-leukemia, lymphoma, myeloma, or in a broader sense graft-versus-tumor effects renders immunotherapy more time consuming. Hence, eradication of rapidly growing bulky tumors may be difficult or impossible to achieve. Considering the fact that optimal immunotherapy may be accomplished in patients treated at the stage of minimal (MRD) disease, in patients with hematological malignancies and chemosensitive solid tumors a stage of MRD may be best achieved following administration of myeloablative high-dose chemotherapy or chemoradiotherapy supported by autologous stem cell transplantation (autoSCT). Taken together, immunotherapy following autoSCT may provide an ideal combination for improving the cure rate of otherwise incurable cancers, especially if tumor cells may respond to cytokine-mediated immunotherapy or cell-mediated cytokine-activated immunotherapy. Following lymphocyte depletion in the course of autoSCT, adoptive transfer of alloreactive or tumor-reactive lymphocytes may be much more effective due to the preponderance of anticancer effector cells on the one hand, and elimination or depletion of the patient's regulatory cells that may downregulate anticancer effector mechanisms.