Hematopoietic Recovery after Allogeneic Transplantation Using G-CSF-Mobilized and Cryopreserved Peripheral Blood Stem Cells (PBSC).

Abstract

Although PBSC is being used more often, the long-term reconstitution kinetics of donor-derived hematopoiesis have not yet been fully determined particularly in PBSC transplantation with a reduced-intensity regimen (RIST). This study focused on the long-term follow-up of hematopoiesis in recipients who underwent allogeneic transplantation with G-CSF-mobilized and cryopreserved PBSC from an HLA-matched related donor from June 1999 to January 2004. A total of 144 patients were analyzed ; 55 received conventional stem cell transplantation (CST) with a myeloablative regimen, whereas 89 received RIST. After PBSC were mobilized by 3 to 5 days of subcutaneous injection of G-CSF at a dose of 10μg/kg/day, leukapheresis was performed using a Spectra (Gambro) or AS104 (Fresenius) cell separator. Apheresed products were centrifuged (270 x g, 20 min) and depleted of platelets. Cells were then cryopreserved with 10% DMSO, 20% autologous plasma and RPMI 1640 using a programmed freezer, and stored in LiqN2 until use. All patients received G-CSF 5μg/kg/day starting from day 6 after transplantation. Hematological data were examined during recovery, at day 100, 1 year and 2 years. The median number of infused CD34+ cells was 3. 9 x 106/kg (range, 1.8–7.8) in CST and 3.5 x 106/kg (1.4–7.8) in RIST. The median number of days to ANC > 0.5 x 109/l and PLT > 50 x 109/l were, respectively, 13 (9–25) and 14 (7–83) in CST, and 11 (1–15) and 12 (1–44) in RIST. There was no engraftment failure, and no significant relationship was observed between the CD34+ cell dose (at least in the range of 2.0 x 106/kg) and the speed of engraftment in either group. Grade II to IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD occurred in 23/55 cases (42%) and 12/43 (28%) in CST, and in 37/89 (42%) and 19/60 (32%) in RIST, respectively. Each blood component in peripheral blood in non-relapsed patients remained essentially within the normal range (WBC >3x109/l, Hb >10g/dl, PLT >1x1011/l) in 21/43 cases (49%) at day 100, in 25/26 (96%) at 1 year, and in 14/14 (100%) at 2 years in the CST group, whereas in the RIST group these values were 24/60 (40%) at day 100, 29/38 (76%) at 1 year, and 15/16 (94%) at 2 years, probably due to increased non-relapse complications including GVHD, etc. These results suggest that a CD34+ cell dose in PBSC of 2.0 x 106/kg before cryopreservation appears to be a good indication for stable long-term hematological recovery for both CST and RIST.