R Foa1. 1. Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Clinica Medica, Torino, Italy.
Abstract
PURPOSE: To discuss the possibility that interleukin-2 (IL-2)-based immunotherapeutic protocols may have a role in the management of acute leukemia. DESIGN: The preclinical results that have led to the clinical use of IL-2 in acute leukemia will be reviewed. The clinical data obtained with the administration of IL-2 to acute leukemia patients in different phases of their disease will be discussed, together with the clinicohematologic and immunologic modifications induced following the infusion of IL-2. Finally, the possibility that limitations associated with the exogenous administration of high-dose IL-2 may be circumvented by engineering techniques aimed at inserting the IL-2 gene directly into the tumor cells, will be addressed. RESULTS: The data indicate that high-dose IL-2 may be administered to acute leukemia patients. Toxicity, recorded in all patients, appears to be controllable using a continuous intravenous (i.v.) infusion protocol based on a daily dose-escalating administration. Complete remissions have been documented in acute myeloid leukemias (AMLs) with a limited, but detectable proportion of residual marrow blasts. Numerous phenotypic and functional changes have been recorded within the immune system of the host. Using retroviral vectors, the IL-2 gene may be productively transduced into human acute leukemia cell lines. CONCLUSION: IL-2 appears to represent a therapeutic option for AML patients with limited/minimal residual disease. The results of the ongoing randomized trials in patients in first or second remission are awaited.
PURPOSE: To discuss the possibility that interleukin-2 (IL-2)-based immunotherapeutic protocols may have a role in the management of acute leukemia. DESIGN: The preclinical results that have led to the clinical use of IL-2 in acute leukemia will be reviewed. The clinical data obtained with the administration of IL-2 to acute leukemiapatients in different phases of their disease will be discussed, together with the clinicohematologic and immunologic modifications induced following the infusion of IL-2. Finally, the possibility that limitations associated with the exogenous administration of high-dose IL-2 may be circumvented by engineering techniques aimed at inserting the IL-2 gene directly into the tumor cells, will be addressed. RESULTS: The data indicate that high-dose IL-2 may be administered to acute leukemiapatients. Toxicity, recorded in all patients, appears to be controllable using a continuous intravenous (i.v.) infusion protocol based on a daily dose-escalating administration. Complete remissions have been documented in acute myeloid leukemias (AMLs) with a limited, but detectable proportion of residual marrow blasts. Numerous phenotypic and functional changes have been recorded within the immune system of the host. Using retroviral vectors, the IL-2 gene may be productively transduced into humanacute leukemia cell lines. CONCLUSION:IL-2 appears to represent a therapeutic option for AMLpatients with limited/minimal residual disease. The results of the ongoing randomized trials in patients in first or second remission are awaited.