INTERLEUKIN-2 THERAPY AFTER BONE-MARROW OR STEM-CELL TRANSPLANTATION FOR HEMATOLOGIC MALIGNANCIES

PURPOSE Autologous or allogeneic bone narrow transplantation (BMT) or stem cell transplantation (SCT) for advanced hematologic malignancies is associated with a high relapse rate, Ir has been postulated that re combinant interleukin-2 (rIL-2) administered as consolidative immunoth erapy early after BMT or SCT, at a time of minimal residual disease, m ight reduce the relapse rate, We review here preliminary results from a series of studies designed to investigate the safety, immunomodulato ry effects, and clinical benefits of rIL-2 therapy following autologou s and allogeneic BMT and SCT, PATIENTS AND METHODS Patients with hemat ologic malignancies underwent autologous or allogeneic BMT or SCT and received rIL-2 by continuous intravenous infusion a median of 33 to 56 days later. In all trials, the rIL-2 regimen consisted of a moderate induction dose for 4 ro 5 days in the hospital, 4 to 6 days of rest, a nd a low maintenance dose for 10 daps in the outpatient setting. A pha se I trial of Roche rIL-2 after autoBMT, a feasibility trial of autolo gous lymphokine-activated killer cells with rIL-2, and another phase I /II trial of Chiron rIL-2 after autoBMT were performed. A similar phas e I trial of IL-2 after alloBMT was also performed in children with ac ute leukemia beyond first complete remission. RESULTS An rIL-2 regimen has been identified that can be tolerated early after transplantation . Administration of this rIL-2 regimen induces marked increases in CD3 +CD8+ T lymphocytes and CD3-CD56+ natural killer cells and enhances th eir antitumor cytolytic activity. Encouraging but somewhat inconsisten t clinical outcomes were noted in phase I/II trials in patients with l ymphoma and acute myeloid leukemia CONCLUSIONS The results of phase I/ II trials are sufficiently encouraging to justify prospectively random ized phase III trials to determine whether rIL-2 after autologous SCT will reduce the rate of posttransplantation relapse and improve surviv al in patients with advanced hematologic malignancies.