Mobilization of Peripheral Blood Stem Cells from Normal Donors
I. INTRODUCTION Mobilized peripheral blood stem cells (PBSCs) are increasingly used for allogeneic transplantation following myeloablative or nonmyeloblative therapies (1,2). PBSCs earned a well-deserved reputation for supporting rapid and durable trilineage hematological engraftment in transplantation. Other perceived advantages of autologous PBSCs included improved patient tolerance of the harvesting procedure (without general anesthesia) and possibly diminished tumor contamination (3-5). The ability of autologous and syngeneic mobilized PBSCs to provide long-term hematopoietic reconstitution suggested that PBSC grafting might also be successful in allogeneic transplantation. Allogeneic PBSC transplants in animals supported the hypothesis that long-term sustained engraftment was possible (6,7). Syngeneic transplants employing only mobilized PBSCs were successful in patients with malignancies (8). The first patient transplanted with allogeneic PBSCs from a human leukocyte antigen (HLA)–matched sibling donor engrafted, but sustained engraftment could not be evaluated, since the patient died of Aspergillus infection (9). Within the past 4 years, hundreds of patients have been transplanted using mobilized PBSC allografts instead of bone marrow. Reports on these patients have demonstrated that hematopoietic recovery using mobilized allogeneic PBSCs is rapid, complete (all lineages), and durable; the latter being demonstrated by cytogenetics or molecular markers (10-16). Neutrophil (500/µL) and platelet recovery (20,000/µL) is typically between 9 and 15 days (17,18) in HLA-matched sibling transplants, but longer engraftment times for neutrophils (16-33 days) have been reported in HLA-mismatched transplants (19). Only one graft failure was reported in 62 patients who received only mobilized PBSC allografts; in which case, the patient received PBSCs after failing an allogeneic marrow transplanta-
tion from the same donor (19). Thus, similar to the replacement of autologous marrow grafts with mobilized PBSC collections, allogeneic PBSCs from matched sibling donors are increasingly supplanting marrow as the graft of choice for hematopoietic recovery following myeloablative or nonmyeloablative therapies. Allogeneic PBSC transplants using matched unrelated donors are currently under clinical investigation. Intensive efforts have focused on methods to optimize the mobilization and collection of PBSCs from healthy individuals, since widespread successful utilization of allogeneic PBSCs is dependent on a variety of factors, including ethical considerations, which would impel physicians to harvest allogeneic PBSCs using regimens with the least possible risk, discomfort, and expense to the patient/donor, and quality of the grafts, which is determined by the content of primitive as well as committed hematopoietic cells. In this chapter, we will attempt to review the current practices and controversies regarding mobilization of PBSCs from normal donors. Important discussions are directed toward donor eligibility for PBSC versus marrow grafts; the dose and scheduling of cytokine regimens; the leukapheresis procedure, including processing volume and timing; the effects of growth factor administration and leukapheresis on the donor; and issues contributing to the choice between marrow and PBSCs for allogeneic transplantation.