Pilot trial of interleukin-2 with granulocyte colony Stimulating factor for the mobilization of progenitor cells in advanced breast cancer patients undergoing high-dose chemotherapy: Expansion of immune effectors within the stem-cell graft and post-stem-cell infusion

J. A. Sosman*, P. Stiff, S. M. Moss, P. Sorokin, B. Martone, R. Bayer, K. Van Besien, S. Devine, W. Stock, D. Peace, Y. Chen, C. Long, D. Gustin, M. Viana, R. Hoffman

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Purpose: To evaluate whether administration of interleukin-2 (IL-2) with granulocyte colony-stimulating factor (G-CSF) improves mobilization of immune effector cells into the stem-cell graft of patients undergoing high-dose chemotherapy and autografting. Patients and Methods: We performed a trial of stemcell mobilization with IL-2 and G-CSF in advanced breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, thiotepa, and carbopatin and stem cells followed by IL-2. The trial defined immune, hematologic, and clinical effects of IL-2 in this setting. Results: Of 32 patients enrolled, nine received G-CSF alone for mobilization. Twenty-one of 23 patients mobilized with IL-2 plus G-CSF had stem cells collected with more mononuclear cells than those receiving G-CSF (19.3 v 10.4 × 108/kg; P = .006), but fewer CD34+ progenitor cells (6.9 v 22.0 × 106/kg; P = .049). The IL-2 plus G-CSF-mobilized patients had greater numbers of activated T (CD3+/CD25+ cells (P = .009). natural killer (NK; CD56+) cells (P = .007), and activated NK (CD56 bright+ cells (P = .039) than those patients mobilized with G-CSF. NK (P = .042) and lymphokine activated killer (LAK) (P = .016) activity was increased in those mobilized with IL-2 + G-CSF, whereas G-CSF-mobilized patients had a decline in cytolytic activity. In the third week posttransplantation, immune reconstitution was superior in those mobilized with IL-2 plus G-CSF based on greater numbers of activated T cells (P = .003), activated NK cells (P = .04), and greater LAK activity (P = .003). The 16 of 21 IL-2 + G-CSF-mobilized patients with adequate numbers of stem cells (> 1.5 × 106 CD34+ cells/kg) collected engrafted rapidly posttransplantation. Conclusion: The results demonstrate that G-CSF + IL-2 can enhance the number and function of antitumor effector cells in a amobilized autograft without impairing the hematologic engraftment, provided that CD34 cell counts are more than 1.5 × 106 cells/kg. Mobilization of CD34+ stem cells does seem to be adversely affected. In those mobilized with IL-2 and G-CSF, post-stem-cell immune reconstitution of antitumor immune effector cells was enhanced.

Original languageEnglish (US)
Pages (from-to)634-644
Number of pages11
JournalJournal of Clinical Oncology
Volume19
Issue number3
DOIs
StatePublished - Feb 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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