Comparison of two leukapheresis programs for computerized collection of blood progenitor cells on a new cell separator

BACKGROUND : Peripheral blood progenitor cells (PBPCs) can be collected on various cell separators. Two leukapheresis programs (LP-MNC and LP-PBSC-Lym) were evaluated for computerized collection of PBPCs on a new cell separator. STUDY DESIGN AND METHODS : Leukapheresis assisted by the LP-MNC or LP-PBSC-Lym software was performed for the harvesting of PBPCs in 52 oncology patients after chemotherapy plus G–CSF treatment and in 18 healthy subjects after G–CSF mobilization alone. RESULTS : A total of 38 components from 33 donors via LP-MNC and 43 components from 37 donors via LP-PBSC-Lym were collected with a median of one (range, one to two) standard-volume leukapheresis procedures (9.2-13.3 L) per donor. There were no significant differences between the two groups concerning median counts of WBCs, CD34+ cells, CD34+ cell yields per harvest, and CD34+ cell yields of cumulative harvests. The blood cell counts after leukapheresis revealed that the LP-MNC resulted in significantly higher platelet loss than LP-PBSC-Lym (p = 0.024): 35.9 percent (range, 19.2%-66.1%) versus 29.7 percent (11.6%-52.3%). Regarding the CD34+ cell collection efficiency, the LP-MNC program was significantly better than the LP-PBSC-Lym program (p < 0.001): 77.5 percent (range, 35.5%-98.9%) versus 58.3 percent (range, 20.4%-98.9%). However, concentrates collected by the LP-PBSC-Lym program had significantly higher percentages of MNCs (p < 0.001) and CD34+ cells (p = 0.028) than harvests with the LP-MNC program: 90 percent (range, 69%-99%) versus 70 percent (range, 35%-98%) and 1.2 percent (range, 0.2%-7.3%) versus 0.7 percent (range, 0.2%-6.0%), respectively. No leukapheresis-related serious adverse events were seen, and time for hematopoietic engraftment was equivalent to data published in the literature. CONCLUSION : The LP-MNC program shows a significantly better CD34+ cell collection efficiency than the LP-PBSC-Lym program. However, collections with the LP-MNC program result in PBPC components with a lower MNC and CD34+ cell concentrations and a higher apheresis-related loss of patient's platelets

Dose Rate and Fractionation of Total Body Irradiation in Dogs Short and Long Term Effects.

Variations of regimens of total body irradiation (TBI) were investigated in the dog as a preclinical model for bone marrow transplantation. Inactivation of hemopoietic precursor cells (CFU-GM) was studied following irradiation of marrow in vitro, following TBI at sublethal doses in vivo and following autologous transplantation of marrow obtained after sublethal TBI. Inactivation and recovery of CFU-GM as well as restoration of hemopoiesis following autologous transplantation was independent of the dose rate, but nadirs of blood counts were lower following sublethal TBI with the higher dose rate. Acute non-hemopoietic toxicity of TBI depended on the dose, the dose rate and the total treatment time and not on the fractionation regimen. At a total dose of 25 Gy acute mortality was prevented by prophylactic administration of oral, non-absorbable antibiotics. Late mortality was due to degenerative and autoimmune-like disorders with or without infections and to malignant tumors. Evaluation of long-term survival is still preliminary, since surviving dogs of two groups (10 Gy as single dose, 25 Gy as hyperfractionated TBI) have not yet reached the median survival time of their group. So far, long-term survival depended on the total dose (p = 0.05) and, possibly, the fractionation regimen (p = 0.12). The latency period until development of malignant tumors was influenced by the total doses given in the same treatment time (p = 0.05) and by the total treatment time for equal doses (p = 0.04). It was concluded that TBI at a low dose rate may give the best therapeutic ratio of inactivation of hemopoietic precursor cells to acute toxicity. A possible benefit of hyperfractionation on long-term survival due to less toxicity has to be weighed against less effective inactivation of clonogenic hemopoietic precursors and less effective immunosuppression seen in allogeneic transplantation

Immunological characterization of canine hematopoietic progenitor cells.

Canine hematopoietic progenitor cells were characterized by separation with monoclonal antibodies. Depleted and enriched fractions were studied for growth of CFU-GM in semisolid agar and for repopulating capacity of lethally irradiated dogs. CFU growth was not reduced by depletion of marrow using monoclonal antibodies F 3-20-7 (anti-dog Thy-1), MT606 (anti-human CD6), and IOT2a (anti-human DR). CFU growth was variable following treatment with the anti-canine T-cell antibody MdT-P1 and immunomagnetic bead separation. It was regularly enriched when MdT-P1 treatment was followed by immunorosetting with staphylococcal protein A-loaded sheep red blood cells and density gradient separation. Lethally irradiated dogs were reconstituted by autologous marrow depleted of MdT-P1-positive cells using immunorosetting and density gradient centrifugation, whereas immunomagnetic bead-depleted marrow was ineffective. Fluorescence-activated cell sorting showed enrichment of hematopoietic progenitor cells in the weakly MdT-P1-positive fraction