• To determine the CD34 plus cell content of an AMD3100 mobilized PBPC in comparison to G-CSF mobilized PBPC from the same healthy donor. [ Time Frame: Day 1 (cells are counted over 24 hours after AMD3100) ] [ Designated as safety issue: No ]
  

• 1) Determine the CD34 plus cell mobilization kinetics following subcutaneous dose of AMD3100. 2) Yields of hematopoietic progenitor cells, immune cells, and other cellular subsets collected by apheresis; and 3) safety profile of AMD3100. [ Time Frame: Through day 7 ] [ Designated as safety issue: Yes ]
  

Drug: AMD3100
N/A

Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoetic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment.

Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the peripheral blood stem cell graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be associated with bone pain, headache, myalgia and rarely life threatening side effects like stroke, myocardial infarction and splenic rupture.

AMD3100, is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. CXCR4 is present on CD34+ hematopoetic progenitor cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis. Recently, a published report demonstrated that large numbers of CD34+ cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. Remarkably, the number of CD34+ cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34+ cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization. Although the study population is relatively small, side-effects to this agent have been mild and transient with no serious complications having been reported. The ability to collect a large quantity of PBPC with a single injection of this drug makes this an attractive agent for mobilizing donors of allogeneic PBPC. However, the immunologic profiles of AMD3100 mobilized cells, in terms of lymphocyte content (T cell, B cell, NK cell, immuno-regulatory T cell), T cell polarization status (TH1 versus TH2), status of antigen presenting cells (DC1 versus DC2), alloreactive potential, and preservation of reactivity to infectious agents (e.g. EBV, CMV) are unknown. Consequently, whether AMD3100 mobilized PBPC would be suitable for use as an allograft is uncertain. In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization. The AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes, NK cells, and antigen presenting cells. AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes.