Individualized leukapheresis of hematopoietic cells for cellular therapies

Abstract: Hematopoietic stem and progenitor cells from blood (HSC) are collected by leukapheresis from patients after mobilization with G-CSF +/- chemotherapy to be used in autologous transplantation. The established method to measure the content of HSC in peripheral blood and HSC collections is by their expression of the CD34-antigen. The optimal dose of HSC for transplantation is today considered to be >5x 106 CD34+ cells /kg bodyweight for prompt hematological recovery of all three lineages whereas a dose of 2-5 x106 /kg Can lead to delayed recovery of platelets. To optimize and individualize each leukapheresis in regard of timing, the procedure in itself, the volume processed and the number of harvests needed to reach target numbers of CD34+ cells would be beneficial for both patients and the leukapheresis center as well as cost-saving. The leukapheresis technology is used to collect other cell types as well, at our center mainly monocytes to be used as a source for dendritic cell (DC) generation. The amount of DCs available for immunotherapy depends on the amount and quality of the monocytes collected. To optimize the leukapheresis procedure for monocyte collection (enrichment and purity as well as the absolute numbers collected) is essential for the final outcome of the numbers and the quality of dendritic cells. In summary, it is demonstrated that: By analysis of on-line samples and manual adjustments of the hematocrit in the collect-line it is possible to increase the yield of CD34+ cells, GM-CFU and mononuclear cells in HSC collections. By analyzing on-line samples during monocyteleukapheresis we can direct the leukapheresis towards optimized monocyte enrichment and decide the volume to be collected to reach target numbers of monocytes. With the prediction of CD34+ yields in patients that mobilizes CD34+ adequately as well as in patients that have a poor mobilization response we can adapt the HSC collections for each individual patient in regards of when to start collections, adjust the volume processed during leukapheresis according to target values of CD34+ cells and avoid unnecessary procedures.