Jaroscak, et al. (2003). Augmentation of umbilical cord blood (Ucb) transplantation with ex-vivo expanded UCB cells: results of a phase I trial using the Aastrom Replicell system.

[Wise Young]

• Jaroscak J, Goltry K, Smith A, Waters-Pick B, Martin PL, Driscoll T, Howrey R, Chao N, Douville J, Burhop S, Fu P and Kurtzberg J (2003). Augmentation of umbilical cord blood (Ucb) transplantation with ex-vivo expanded UCB cells: results of a phase I trial using the Aastrom Replicell system. Blood Summary: Allogeneic stem cell transplantation with umbilical cord blood (UCB) cells is limited by the cell dose a single unit provides recipients. Ex-vivo expansion is one strategy to increase the number of cells available for transplantation. Aastrom Biosciences Inc. developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSC). Cells are expanded in media supplemented with fetal bovine serum, horse serum, PIXY321, flt-3 ligand, and erythropoietin. We performed a phase I trial augmenting conventional UCB transplant with ex-vivo expanded cells. Twenty-eight patients were enrolled on the trial between 10/8/97 and 9/30/98. UCB cells were expanded in the device then administered as a boost to the conventional graft on post transplant day 12. While expansion of total cells and colony-forming units (CFU) occurred in all cases, the magnitude of expansion varied considerably. The median fold increase in nucleated cells was 2.4 (range, 1.0-8.5), in CFU-GM was 82 (range, 4.6-266.4), and in CD34(+) lineage negative (lin(-)) was 0.5 (0.09-2.45). CD3(+) cells did not expand under these conditions. Clinical scale ex-vivo expansion of UCB is feasible, and the administration of ex-vivo expanded cells is well tolerated. Augmentation of UCB transplants with ex-vivo expanded cells did not alter the time to myeloid, erythroid or platelet engraftment in 21 evaluable patients. Recipients of ex-vivo expanded cells continue to have durable engraftment with a median follow-up of 47 months (range, 41-51 ). A randomized phase II study will determine whether augmenting UCB transplants with ex-vivo expanded UCB cells is beneficial. Pediatric and Adult Bone Marrow Transplant Programs, Duke University Medical Center, Durham, NC, USA.