INTERLEUKIN-2-ACTIVATED HEMATOPOIETIC STEM-CELL TRANSPLANTATION FOR BREAST-CANCER - INVESTIGATION OF DOSE LEVEL WITH CLINICAL CORRELATES

Incubating hematopoietic stem cells with IL-2 in vitro for 24 h genera tes cytotoxic T cells. When infused into patients, these cells may sti mulate a graft-versus-tumor (GVT) effect. This clinical trial was desi gned to assess the ability of IL-2 activated peripheral blood stem cel ls (PBSC) to reconstitute hematopoiesis, to investigate dose levels an d dose-limiting toxicities of IL-2, and to evaluate clinical results a nd preliminary laboratory effects using a combination of IL-2-activate d autologous PBSC followed by IL-2 after transplantation. Sixty-one wo men with stage II-IV breast cancer were treated, After the administrat ion of carboplatin (200 mg/m(2)/day for 3 days) and cyclophosphamide ( 2 g/m(2)/day for 3 days), patients received autologous PBSC that were cultured in IL-2 for 24 h followed by parenteral administration of IL- 2 beginning the day of transplantation. Three escalating doses of IL-2 were evaluated with increasing duration up to 4 weeks. Of the 57 pati ents receiving IL-2 after tranplantation, 19 patients (33.3%) were una ble to complete the planned course of IL-2 therapy due to persistent f evers (n = 9), diarrhea (n = 2), pulmonary capillary leak syndrome (n = 3), development of a rash (n = 1), atrial fibrillation (n = 1), or p atient's request (n = 3). One death occurred during hospitalization. E ngraftment of neutrophils occurred on day 11.5 (mean; range 8-21 days) and platelets on day 11.7 (mean; range 7-33 days). The maximal tolera ted dose of IL-2 was 6 x 10(5) IU/m(2)/day for 4 weeks. Disease-free s urvival rates for all stages were comparable to current reports in the literature, Preliminary laboratory evaluations include FACScan analys is of the IL-2 activated PBSC demonstrating an increased percentage of CD3(+), CD25(+), HLA-DR+ T cells. Phenotypically similar cells were p resent in peripheral blood samples of patients when tested 15 days aft er transplantation. This study demonstrates successful engraftment wit h IL-2-activated PBSC after high-dose chemotherapy for women with stag e II-IV breast cancer. The regimen is feasible and, although toxicitie s are common, they are manageable and correlate with increasing dose a nd duration of IL-2.