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Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected
Authors:Kenneth R. Meehan  Laleh Talebian  Jillian Wu  John M. Hill  Zbigniew M. Szczepiorkowski  Charles L. Sentman  Marc S. Ernstoff
Affiliation:1. Blood and Marrow Transplant Program, Dartmouth Hitchcock Medical Center, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, New Hampshire, USA;2. Cellular Therapy Center and Blood Bank/Transfusion Medicine Service, Dartmouth Hitchcock Medical Center, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, New Hampshire, USA;3. Department of Immunology and Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, New Hampshire, USA;4. Section of Hematology and Oncology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, New Hampshire, USA
Abstract:Background aimsA phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells.MethodsInterleukin (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).ResultsToxicities 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.ConclusionsImmune 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.
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