Peripheral blood stem cells in acute myeloid leukemia: biology and clinical applications.

Clinical application of circulating stem cells for autologous transplantation is steadily expanding. It has become increasingly clear that mobilized peripheral blood progenitor cells (PBSC) induce faster hematopoietic recovery, fewer febrile days, lower transfusion requirement and shorter hospitalization than bone marrow (BM)-derived cells.More recently, rapid and sustained engraftment has also been reported using granulocyte colony-stimulating factor (G-CSF). This review analyzes the most recent advances in this field, addressing clinical and biological issues relevant to the use of autologous PBSC for AML patients. Conclusions: Autologous BMT has been widely used as consolidation therapy in AML patients in first or second remission; however, delayed hematopoietic engraftment occurs in a substantial proportion of patients resulting in significant morbidity and mortality. This is mainly due to the adverse effects of prior intensive chemotherapy on BM harvest, a decrease in the normal stem cell pool in leukemic patients and, perhaps, toxic damage to the marrow microenvironment. Thus, several groups have investigated the use of circulating progenitor cells with the twofold aim of reducing transplant-related toxicity and widening the number of potential candidates for myeloablative therapy with the support of autologous stem cells. As for hematopoietic reconstitution, previous studies have provided evidence that PBSC transplantation may offer some advantages over BM autografting. However, crucial issues such as asynchronous mobilization of normal vs leukemic cells and potential contamination of PBSC collections, timing of PBSC harvest, detection of minimal residual disease, and the role of growth factors to accelerate hematological recovery and optimize stem cell collection have not been fully addressed. In the present paper, the latest advances in his field have been reviewed with special focus on the biology of putative leukemic stem cells; operative guidelines have also been provided for those investigators who wish to design proper clinical trials on PBSC autotransplantation in acute leukemia. Definitive answers regarding the role of PBSC will be coming from a large European randomized trial which is currently comparing peripheral blood stem cell and BM-derived graft.