Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected

Cytotherapy. 2010 Dec;12(8):1013-21. doi: 10.3109/14653249.2010.515580. Epub 2010 Sep 27.

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 x 10⁶ CD34+ cells/kg (median; range 1.9-6.6 x 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 x 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Capillary Leak Syndrome / etiology
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / physiopathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Interleukin-2 / administration & dosage
  • Leukapheresis
  • Lymphocyte Activation
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Transplantation, Autologous

Substances

  • Interleukin-2
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor