Peripheral blood stem cell collection from healthy donors for allogeneic transplantation

Abstract

There is great interest in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, based on the good results seen with autologous PBSC infusion. Reasonable caution exists regarding the use of allogeneic PBSC for transplantation because of donor toxicities due to rhG-CSF administration and the risk of graft-versus-host-disease (GVHD) in the recipient because of the large number of T-cell infused. We present preliminary data on allogeneic PBSC collections and transplantation in ten patients affected by advanced leukemia (eight patients), severe aplastic anemia (one patient) and sickle cell anemia (one patient). Seven donors were HLA-identical siblings, while the other three were mismatched for three, two and one locus, respectively. All donors received rhG-CSF at a dose of 12 μg/kg for a mean of 5 days. Leukaphereses were performed with the aim of collecting a minimum of 5 × 10 6/kg (recipient's weight) CD 34+ cells. Collection timing was determined by monitoring CD 34+ cells in the donor's peripheral blood from the second day of rhG-CSF therapy. The PBSC collections yielded a mean of 10.05 × 10 8 MNCs/kg and of 10.48 × 10 6 CD 34+ cells/kg (recipient's weight). PBSC were immediately infused after collection in patients given myeloablative therapy. Engraftment was observed in each patient at a mean of 13.2 days for an absolute neutrophil count (ANC) more than 0.5 × 10 9/L and of 26.5 days for a platelet count of more than 20 × 10 9/L. Eight patients experienced no or moderate acute GVHD, whereas two patients died of grade 4 GVHD, nothwithstanding GVHD prophylaxis with cyclosporine and prednisone. Two other patients died of viral and fungal infections, respectively, despite prophylaxis. The remaining six patients are alive between 58 and 430 days after transplant. Our results document that allogeneic PBSC are capable of engraftment after a myeloablative regimen. Controlled trials are necessary to compare the potential benefits of this approach with the results obtained in allogeneic bone marrow transplantation (BMT).