Recombinant Interleukin-2 Treatment Before and After Autologous Stem Cell Transplantation in Hematologic Malignancies: Clinical and Immunologic Effects

Autologous bone marrow transplantation (ABMT) for hematologic malignancies is associated with a high relapse rate. Interleukin-2 (IL-2) administration is a therapy that may prevent relapse if used when the tumor burden is minimal. In this study we administered recombinant IL-2 (rIL-2) therapy to 12 patients affected by hematologic malignancies either before or after autologous stem cell transplantation (ASCT). rIL-2 was given by a 6 day continuous intravenous infusion with escalating doses, up to 18 x 10⁶/m²/day, depending on patient tolerance. The functional immune responses of the patients were assessed as natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activities and in vitro interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) synthesis. During rIL-2 treatment, the expected side effects occurred; only 3 patients, who showed severe cardiovascular toxicity, required suspension of the treatment. All toxicities reversed after the end of the therapy. Immunologic monitoring was carried out the day before starting rIL-2 infusion and then repeated on days 3, 7, and 14 after rIL-2 was discontinued. Following every rIL-2 course, a pronounced increase in CD3⁺, CD8⁺, CD56⁺ cells was found, with a peak value on day 3. The NK and LAK activities showed a significant increase on day 3 (p < 0.001) over pretherapy values; the increase lasted until day 14, although the difference at later time points was not significant. Before transplant the synthesis of both IFN-γ and TNF-α decreased following rIL-2 therapy, whereas higher levels of these lymphokines were found after posttransplant rIL-2 courses. These results extend the studies of immunologic monitoring of patients receiving rIL-2 and demonstrate the clinical feasibility of the pre- and posttransplant rIL-2 administration.