AMD 3100 (Mozobil Plerixafor) to Mobilize Stem Cells for Donation
Condition: Healthy
Intervention: AMD3100 (Mozobil plerixafor)
Intervention description: AMD 3100 (Mozobil plerixafor)mobilized peripheral blood hematopoietic progenitor cells from healthy volunteers will be characterized by cellular content and immunological properties.
Intervention MeSH terms: Plerixafor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hematopoietic Stem Cells; Mobilization; Alloreactivity; T Cell Polarization; Dendritic Cells; Plerixafor; Mozobil; Healthy Volunteer (HV)

Summary:

      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 CXC- chemokine receptor 4 (CXCR4). CXCR4 is present on
      cluster of differentiation 34 (CD34)+ hematopoetic progenitor cells and its interaction with
      stromal cell derived factor 1 (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.

      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, natural killer (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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Mobilization and collection of PBPC using G-CSF at least 60 days prior to
                  protocol enrollment (stem cell donors enrolled on Branch transplant protocols or
                  healthy volunteers enrolled on 96-H-0049: Use of granulocyte colony stimulating
                  factor mobilized leukapheresis collections from healthy volunteers).

               2. Ages greater than or equal to 18 years and less than or equal to 80 years.

               3. Normal renal function: creatinine less than 1.5 mg/dl.

               4. Normal liver function: total bilirubin less than 1.5mg/dl, alanine
                  aminotransferase (ALT) 6 -41 U/L, aspartate aminotransferase (AST) 9-34 U/L.

               5. Normal blood count: white blood cell (WBC) 3000-10000/mm(3)

                  granulocytes greater than 1500/mm(3)

                  platelets greater than 150,000/mm(3)

                  hemoglobin (females greater than 11.1 g/dl, males greater than 12.7 g/dl).

               6. Subject must be eligible for normal blood donation and fit to undergo apheresis
                  procedure (antecubital veins must be adequate for peripheral access during
                  apheresis).

               7. Ability to comprehend the investigational nature of the study and provide
                  informed consent.

        EXCLUSION CRITERIA: Any of the Following

          1. Active infection or history of recurrent infection- hepatitis B and C (HBsAg,
             Anti-HBc, Anti-HCV), HIV and human T- lymphocytic virus (HTLV-1).

          2. History of autoimmune disease such as rheumatoid arthritis, systemic lupus
             erythematous.

          3. History of cancer within the past 5 years excluding basal cell or squamous cell
             carcinoma of the skin.

          4. History of any hematologic disorders including thromboembolic disease.

          5. History of cardiac disease such as uncontrolled hypertension, peripheral vascular
             disease, myocardial infarction, cardiac arrhythmias OR related symptoms such as
             tachycardia, chest pain, shortness of breath which have required medical intervention
             OR treatment or a Framingham coronary disease risk prediction score of greater than
             10% 10 year coronary heart disease (CHD) risk.

          6. History of cerebrovascular disease, transient ischemic attack, or stroke.

          7. Pregnant or lactating.

          8. Severe psychiatric illness: mental deficiency sufficiently severe as to make informed
             consent impossible