Abstract
Background aims. A phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells. Methods. Interleukin (IL)-2 was administered subcutaneously for 11 days, with granulocyte (G)-colony-stimulating factor (CSF) (5 mcg/kg/day) and granulocyte–macrophage (GM)-CSF (7.5 mcg/kg/day) added for the last 5 days. Leukapheresis was initiated on day 11. Thirteen patients were treated (myeloma n = 11, non-Hodgkin's lymphoma n = 2). Results. Toxicities were minimal. IL-2 was stopped in two patients because of capillary leak (n = 1) and diarrhea (n = 1). Each patient required 2.5 leukaphereses (median; range 1–3) to collect 3.2 × 106 CD34+ cells/kg (median; range 1.9–6.6 × 106/kg). Immune mobilization increased the number of CD3+ CD8+ T cells (P = 0.002), CD56+ natural killer (NK) cells (P = 0.0001), CD8+ CD56+ T cells (P = 0.002) and CD4+ CD25+ cells (P = 0.0001) compared with cancer patients mobilized with G-CSF alone. There was increased lysis of myeloma cells after 7 days (P = 0.03) or 11 days (P = 0.02). The maximum tolerated dose of IL-2 was 1 × 106 IU/m2/day. Conclusions. Immune mobilization is well tolerated with normal subsequent marrow engraftment. As cells within the graft influence lymphocyte recovery, an increased number of functional lymphocytes may result in more rapid immune reconstitution.
Acknowledgments
This study was sponsored in part by a grant from the Hitchcock Foundation, Dartmouth Medical School and the Dartmouth-Hitchcock Medical Center (KRM), Leukemia and Lymphoma Society Translational Research Grant 6061-06 (KRM), Dartmouth College NIH COBRE Award (KRM), R21 CA112761 (KRM, MSE) and R01CA095648 (MSE). The research was also funded through an unrestricted research grant from Bayer Pharmaceuticals.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.