Enhancement of the anti-tumor activity of a peripheral blood progenitor cell graft by mobilization with interleukin 2 plus granulocyte colony-stimulating factor in patients with advanced breast cancer

Objective. Autologous interleukin 2 (IL-2)-activated natural killer (NK) ce lls kill a broad spectrum of tumor targets, including breast cancer. We hyp othesized that mobilization with IL-2 and granulocyte colony-stimulating fa ctor (G-CSF) for collection of peripheral blood progenitor cells (PBPC) may enhance the anti-tumor activity of the graft in autograft recipients. We d etermined the dose-limiting toxicity and maximum tolerated dose of subcutan eous IL-2 given with G-CSF for PBPC mobilization, the ability of IL-2 + G-C SF mobilized stem cells to reconstitute hematopoiesis, and the in vitro imm unologic function of the graft in patients with advanced breast cancer. Materials and Methods. Forty-three women with stage IIIA/B or metastatic br east cancer underwent ent mobilization of PBPC with IL-2 administered subcu taneously for 14 days along with G-CSF for the latter 7 days. IL-2 was give n in a dose-escalated manner, with the maximum tolerated dose determined to be 1.75 x 10(6) IU/m(2)/day. Fifteen women with stage IIIA/B or metastatic breast cancer underwent G-CSF mobilization alone and ser ccd as a control group. Fifty-two percent of the patients mobilized with IL-2 at the maximum tolerated dose reached the target number of CD34(+) cells for transplantat ion with three aphereses compared to 93% of control patients who were mobil ized with G-CSF alone. Results. There was no significant impact on time to engraftment of neutroph ils or platelets using either mobilization regimen. The addition of subcuta neous IL-2 to mobilization increased the cytotoxicity of IL-2-activated mon onuclear cells front the PBPC product against the breast cancer cell target , MCF-7, and increased the percentage of NK cells and activated T cells in the PBPC product. The enhanced NK cell number was sustained in the early po sttransplant period. IL-2 + G-CSF mobilization is safe, may lead to a more immunologically functional graft without impairing hematologic recovery, an d thus merits further exploration to evaluate the clinical anti-tumor effic acy of these immunocompetent grafts. Conclusions. Limitations of this combined approach to stem cell mobilizatio n include a decrease in the number of CD34(+) cells mobilized with the comb ined cytokines and the short duration of the increased number of anti-tumor effector cells after transplant. (C) 2000 International Society for Experi mental Hematology. Published by Elsevier Science Inc.