Future paradigm for autologous bone marrow transplantation: tumor purging and ex vivo production of normal stem and progenitor cells.
A major concern in autologous bone marrow transplantation (ABMT) is the possible contamination of the graft with tumor cells. Transplantation of malignant cells, along with normal hematopoietic stem and progenitor cells, may contribute to relapse of disease. Therefore, a growing strategy is to subject autologous marrow to some type of purging procedure to eliminate tumor cells selectively. Transplantation of purged marrow, however, often results in a delayed engraftment associated with (specific or nonspecific) loss of normal stem and progenitor cells during manipulations related to the purging process. A new and burgeoning field in the area of clinical bone marrow transplantation is the ex vivo production of stem and progenitor cells. Several advantages accrue to this strategy. First, this technology makes it possible to expand the stem and progenitor cell population of a small volume of bone marrow or mobilized peripheral blood (MPB), thus lessening the initial tumor burden to be purged. Secondly, ex vivo marrow or MPB expansion may overcome the significant problem of delayed engraftment by rebuilding the numbers of normal stem and progenitor cells necessary for both early and durable engraftment. To accomplish these and other objectives, an automated and closed, clinical-scale bioreactor system, based on continuous perfusion technology, is being developed and will soon enter clinical trials.
Rummel
S A
SA
Aastrom Biosciences, Ann Arbor, MI 48106.
Van Zant
G
G
D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007938:Leukemia / Q000473:pathology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy; D012008:Recurrence; D013234:Stem Cells / Q000473:pathology*; D014182:Transplantation, Autologous