Human haemopoietic progenitor cell mobilization

The advent of recombinant growth factors in the late 1980's has ushered in a new era of haematopoietic progenitor cell (HPC) therapy by facilitating the mobilization of bone marrow progenitors into the circulation where they can be collected in large numbers by apheresis. The work of this thesis has defined the minimal and optimal CD34+ cell threshold requirements for engraftment. The frequency of poor mobilization was noted and risk factors determined. It was demonstrated that poor mobilization was usually a feature of bone marrow damage rather than a specific mobilization defect. In addition, studies in normal volunteers indicated that there was wide inter-individual variation in G-CSF induced progenitor cell mobilization which was not due to G-CSF pharmacodynamic variability. The clinical feasibility of CD34+ cell purification was determined and its clinical limitations documented. These purified cells were used clinically to demonstrate that the increased numbers of T-cells and monocytes in a peripheral blood stem cell (PBSC) transplant compared to bone marrow did not account for the more rapid haematological recovery that occurs with PBSC. These studies answer specific clinically relevant questions and form a platform for future studies in "graft engineering"