107: Evidence of successful allogeneic transplantaiton using cryopreserved peripheral blood stem cells from healthy donors

Abstract

Between Sep 2003 and Dec 2005, the BMT program at Princess Margaret Hospiral (Toronto, ON, Canada) performed 105 transplants using cryopreserved PBSCs from allogeneic related donors. The current study was aimed to evaluate the safety of cryopreservation of PBSCs, to compare the clinical outcomes of cryopreserved PBSCT with fresh PBSCT, and to evaluate the influence of cryopreservation on colony forming unit (CFU) assay data of PBSCs incluidng CFU-GM, BFU-E, CFU-MEG and CFU-GEMM. As a control group, 106 patients receiving fresh PBSCTs between Jun 2001 and Aug 2003 was compared.All patients tolerated well to infusion without significant toxicity. The mean viability of thawed products was 71.2±1.0%. The median transplant dose of TNC and CD34+ cells was 8.9×108/Kg and 5.0×106/Kg, while that of CFU-GM, BFU-E, CFU-MEG and CFU-GEMM was 118, 134, 19, 8.4×104/Kg, respectively. No differences in clinical outcomes were noted between cryo- vs. fresh-PBSCT group: engraftment of neutrophil (p=0.178) or platelet (p=0.785), acute GVHD (p=0.113), chronic GVHD (p=0.673), recurrence (p=0.295), non-relapse mortality (p=0.340), and overall survival (p=0.668). The colony forming activity was reduced by 24.6±2.5% for CFU-GM, 30.5±2.5% for BFU-E, 61.4±3.1% for CFU-MEG, and 21.3±2.1% for CFU-GEMM after cryopreservation. The transplant CD34+ cell dose correlates well with transplant dose of CFU-GM (p<0.001), BFU-E (p<0.001), CFU-MEG (p<0.001) and CFU-GEMM (p=0.049), but not with TNC dose. The group receiving higher transplant CD34+ cell dose showed significantly faster engraftment of neutrophil (≥0.5×109/L, p=0.012) and platelet (≥20×109/L, p=0.013 and ≥100×109/L, p=0.009). Moreover, transplant CFU-MEG dose showed good correlation with engraftment of platelet above 20×109/L (p=0.029), 50×109/L (p=0.003), and 100×109/L (p<0.001). In multivariate analysis, higher CFU-MEG dose was strongly correlated with faster engraftment above 100×109/L when taking into account as a continuous (p<0.001) or categorical variables (p=0.040).Conclusion1)Cryopreserved PBSCT is safe in terms of infusion-related toxocitiy, and showed equivalent transplant outcomes to fresh PBSCT.2)CFU-MEG decreases by 60% after cryopreservation, but other CFUs showed similar decrease as viability.3)Transplant CD34+ cell dose correlated well with engraftment of neutrophil and platelet. However, in terms of stable platelet engraftment (≥100×109/L), CFU-MEG dose seemed to be more important factor than CD34+ cell dose. Between Sep 2003 and Dec 2005, the BMT program at Princess Margaret Hospiral (Toronto, ON, Canada) performed 105 transplants using cryopreserved PBSCs from allogeneic related donors. The current study was aimed to evaluate the safety of cryopreservation of PBSCs, to compare the clinical outcomes of cryopreserved PBSCT with fresh PBSCT, and to evaluate the influence of cryopreservation on colony forming unit (CFU) assay data of PBSCs incluidng CFU-GM, BFU-E, CFU-MEG and CFU-GEMM. As a control group, 106 patients receiving fresh PBSCTs between Jun 2001 and Aug 2003 was compared. All patients tolerated well to infusion without significant toxicity. The mean viability of thawed products was 71.2±1.0%. The median transplant dose of TNC and CD34+ cells was 8.9×108/Kg and 5.0×106/Kg, while that of CFU-GM, BFU-E, CFU-MEG and CFU-GEMM was 118, 134, 19, 8.4×104/Kg, respectively. No differences in clinical outcomes were noted between cryo- vs. fresh-PBSCT group: engraftment of neutrophil (p=0.178) or platelet (p=0.785), acute GVHD (p=0.113), chronic GVHD (p=0.673), recurrence (p=0.295), non-relapse mortality (p=0.340), and overall survival (p=0.668). The colony forming activity was reduced by 24.6±2.5% for CFU-GM, 30.5±2.5% for BFU-E, 61.4±3.1% for CFU-MEG, and 21.3±2.1% for CFU-GEMM after cryopreservation. The transplant CD34+ cell dose correlates well with transplant dose of CFU-GM (p<0.001), BFU-E (p<0.001), CFU-MEG (p<0.001) and CFU-GEMM (p=0.049), but not with TNC dose. The group receiving higher transplant CD34+ cell dose showed significantly faster engraftment of neutrophil (≥0.5×109/L, p=0.012) and platelet (≥20×109/L, p=0.013 and ≥100×109/L, p=0.009). Moreover, transplant CFU-MEG dose showed good correlation with engraftment of platelet above 20×109/L (p=0.029), 50×109/L (p=0.003), and 100×109/L (p<0.001). In multivariate analysis, higher CFU-MEG dose was strongly correlated with faster engraftment above 100×109/L when taking into account as a continuous (p<0.001) or categorical variables (p=0.040). Conclusion1)Cryopreserved PBSCT is safe in terms of infusion-related toxocitiy, and showed equivalent transplant outcomes to fresh PBSCT.2)CFU-MEG decreases by 60% after cryopreservation, but other CFUs showed similar decrease as viability.3)Transplant CD34+ cell dose correlated well with engraftment of neutrophil and platelet. However, in terms of stable platelet engraftment (≥100×109/L), CFU-MEG dose seemed to be more important factor than CD34+ cell dose.