Clinical implications of the heterogeneity of hematopoietic progenitors elicited in peripheral blood by anticancer therapy with cyclophosphamide and cytokine(s)

Clinical investigators have found that the hematopoietic system irreversibly damaged by cancer therapy with myeloablative high doses of chemoradiotherapy can be reconstituted by transplantation of autologous hematopoietic progenitors retrieved from peripheral blood. In comparison with patients transplanted with bone marrow, those who receive peripheral blood progenitors undergo shorter periods of neutropenia and thrombocytopenia, require less platelet and erythrocyte transfusions and, most importantly, experience overall reduced treatment-related morbidity. In this article, we speculate that an explanation for this clinical achievement may be that committed hematopoietic progenitors as well as ancestral uncommitted pluripotent stem cells are retrieved from circulation and transplanted after myeloablative cancer therapy. As indicated by studies in rodents, transplantation of hematopoietic progenitors is followed by two phases of engraftment associated with progenitors at different stages of maturation. An initial phase corresponding to early hematopoietic recovery is produced by committed progenitors, and a second sustained engraftment phase is produced by the pluripotent stem cell. Should this multiphase engraftment model be true of humans also, the exceptionally prompt and sustained blood cell count recovery achieved by transplanting blood progenitor cells may reflect transplantation of heterogeneous progenitors such as committed progenitors and pluripotent stem cells producing an early engraftment phase and then sustained hematopoiesis, respectively.