Peripheral Blood Stem Cell Transplantation: Predictions from Studies in the Mouse

Abstract

Early investigations in mice and dogs demonstrated that transplantable hematopoietic stem cells exist in the peripheral blood, albeit at a much lower frequency than in the borne marrow [1–4]. This has led to the initiation of clinical trials using autologous peripheral blood stem cell (PBSC) transplantation as an alternative to bone marrow stem cell (BMSC) transplantation [5–7] in patients with a variety of malignancies. Patients who benefit most from this treatment are those whose marrow is infiltrated with tumor cells or who have hypoplastic marrows due to extensive prior chemo- and/or radiotherapy [8–10] and those who might not tolerate marrow harvests under general anesthesia [6, 11]. Autologous PBSC transplants have been shown to produce a more rapid recovery of granulocyte counts and immune function than autologous BMSC transplants [7,12], resulting in shorter hospital stays. Although results from clinical trials of PBSC autografting have been encouraging, they must be viewed as short-term since the first successful transplants were performed just 5 years ago. The ability of PBSC alone to provide long-term hematopoietic support and disease-free survival in humans is unknown. Clinical evaluation is made difficult by the long time needed to monitor hematopoietic support in humans, the poor prognosis of these patients, and the often irregular and incomplete ablation of recipient marrow with current high dose, cytotoxic, preparative regimens. Concerns about the quality of hematopoietic reconstitution after PBSC transplantation need to be addressed in future experimental and clinical investigations.