Stem cell self-renewal considerations in bone marrow transplantation

Abstract

Autologous bone marrow transplantation is being used for an increasing number of patients with malignant diseases including Hodgkin's disease, non-Hodgkin's lymphomas, and leukemia. As the success of this procedure improves, there will be continuing concern for the consequences of such treatment. One such concern is the long-term hematopoietic function of recipients following marrow transplantation. There is evidence that bone marrow stem cells are limited in self-renewal capacity. Under circumstances of exposure to certain cytotoxic agents or to great proliferative stress, and following transplantation of marrow into lethally irradiated recipients, bone marrow stem cells undergo a permanent loss of self-renewal capacity. This loss is not initially reflected in peripheral blood counts or in marrow cellularity, but can be determined by a decrease in marrow stem cell content and by assays measuring self renewal. Animal work suggests that survival may be decreased following this loss in self-renewal. In order to limit the adverse effect of this phenomenon, efforts should be made to optimize both the quantity and quality of donor marrow engrafted. This should be possible by transplanting the largest number of marrow cells feasible, and by avoiding prior exposure to cytotoxic agents that are known to damage early stem cells in those patients who are possible candidates for autologous marrow transplantation. The use of lymphokines and peripheral stem cell harvests in transplantation should be carefully monitored as self renewal of engrafted marrow may also be decreased following these new techniques.