title: Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System.
abstract: 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 developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSCs). Cells are expanded in media supplemented with fetal bovine serum, horse serum, PIXY321, flt-3 ligand, and erythropoietin. We performed a phase 1 trial augmenting conventional UCB transplants with ex vivo-expanded cells. The 28 patients were enrolled on the trial between October 8, 1997 and September 30, 1998. UCB cells were expanded in the device, then administered as a boost to the conventional graft on posttransplantation day 12. While expansion of total cells and colony-forming units (CFUs) occurred in all cases, the magnitude of expansion varied considerably. The median fold increase was 2.4 (range, 1.0-8.5) in nucleated cells, 82 (range, 4.6-266.4) in CFU granulocyte-macrophages, and 0.5 (range, 0.09-2.45) in CD34+ lineage negative (lin-) cells. 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 months). A randomized phase 2 study will determine whether augmenting UCB transplants with ex vivo-expanded UCB cells is beneficial.
authors.affiliation: Pediatric and Adult Bone Marrow Transplant Programs, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jaroscak
authors.forename: Kristin
authors.initials: K
authors.lastname: Goltry
authors.forename: Alan
authors.initials: A
authors.lastname: Smith
authors.forename: Barbara
authors.initials: B
authors.lastname: Waters-Pick
authors.forename: Paul L
authors.initials: PL
authors.lastname: Martin
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Driscoll
authors.forename: Richard
authors.initials: R
authors.lastname: Howrey
authors.forename: Nelson
authors.initials: N
authors.lastname: Chao
authors.forename: Judy
authors.initials: J
authors.lastname: Douville
authors.forename: Sue
authors.initials: S
authors.lastname: Burhop
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D003470:Culture Media; D018572:Disease-Free Survival; D005312:Fetal Blood; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000401:mortality; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007223:Infant; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003470:Culture Media