Autologous CD117+ Progenitor Cell Mobilization for Lung Transplantation

The investigators have developed a new therapy utilizing a stem cell found in the bone marrow that is defined by cell surface expression of the protein "cluster of differentiation antigen 117" (CD117). Studies utilizing these stem cells in a mouse heart transplant model have demonstrated significantly improved survival of transplanted hearts, (as much as more than 5 times that seen with untreated heart transplants). In vitro studies in mice also show that these cells work to inhibit the immune system by inhibiting T cell activation/proliferation by both paracrine (primary) and contact-dependent (lesser) mechanisms. Importantly, these stem cells are taken from the intended transplant recipient (autologous) and since these cells are part of their own body normally (in small numbers); these cells are theoretically without risk to the patient. This is very different from other stem cell therapies, which are taken from the donor and as such put the patient at significant risk of developing potentially life-threatening immune reactions. Because the use of our own stem cells is potentially safe - the rapid study, development, and implementation of autologous CD117 stem cell (SC) therapy in human transplant patients is theoretically possible. Therefore, these cells have high impact potential for the field of tissue and organ transplantation as well as auto-immunity - to potentially improve tissue/cellular engraftment, decrease acute rejection, and/or to promote organ transplant tolerance (lack of rejection despite no concomitant immune-suppression). Prior to full clinical development (efficacy trials in humans), the next step is to develop a safe and efficacious means for obtaining relatively large quantities of these cells from potential human recipients. As bone marrow biopsy for cell capture is not without risk (especially to ill potential lung transplant recipients), the investigators propose to use Plerixafor (Mozobil), a CXC-chemokine receptor 4 (CXCR4)-inhibitor to cause efflux of bone marrow-derived CD117+ cells to the peripheral blood for capture by apheresis/positive selection. If successful, the next step will be to perform initial safety studies in human patients awaiting transplantation and normal controls (not a goal of this initial protocol however). These studies have the potential to lead to large-scale clinical efficacy trials and ultimate indication/implementation for human disease(s).

Primary Outcome Measure: The number of circulating CD117+ cells per milliliter (ml) of peripheral blood at baseline and following Plerixafor (Mozobil) treatment (change in peripheral blood CD117+ cells per ml).

Secondary Outcome Measures:

i.) The number of Plerixafor (Mozobil) related adverse events (AEs). ii.) The number of patients with Plerixafor (Mozobil) related AEs iii.) The number of Plerixafor (Mozobil) related serious adverse events (SAEs). iv.) The number of patients with Plerixafor (Mozobil) related serious adverse events (SAEs).

As listed in the package insert, the most common adverse reactions (≥10%) during hematopoietic stem cell mobilization were: diarrhea (37%), nausea (34%), fatigue (27%), injection site reaction (34%), headache (22%), arthralgia (13%), dizziness (11%), and vomiting (10%). It should be noted that the majority of these occurred in patients also undergoing apheresis.