We describe potential problems that may limit the usefulness of peripheral blood stem cells (PBSC) to facilitate the delivery of multiple cycles of high-dose chemotherapy. These include (1) cumulative myelotoxicity and (2) recurrent episodes of febrile neutropenia and a requirement for frequent platelet transfusions as a result of the stubborn persistence of a minimum of 7-9 days of absolute neutropenia and even longer durations of severe thrombocytopenia, despite utilization of PBSC. However, some of these problems may be overcome by shortening the duration of administration of the high-dose regimen with subsequent earlier reinfusion of the stem cell product. The adverse consequences of severe neutropenia could be overcome by the development of prophylactic neutrophil transfusions. These concepts are discussed with presentation of some preliminary data.