title: Clinical Studies of Ex Vivo Expansion to Accelerate Engraftment After Umbilical Cord Blood Transplantation: A Systematic Review.
abstract: Cell dose limits greater use of umbilical cord blood (UCB) in hematopoietic cell transplantation. The clinical benefits of ex vivo expansion need clarity to understand its potential impact. A systematic search of studies addressing UCB ex vivo expansion was conducted. Fifteen clinical studies (349 transplanted patients) and 13 registered trials were identified. The co-infusion of an expanded unit and a second unmanipulated unit (8 studies), the fractional expansion of 12% to 60% of a single unit (5 studies), and the infusion of a single expanded unit (2 studies) were reported. More recently, published studies and 12 of 13 ongoing trials involve the use of novel small molecules in addition to traditional cytokine cocktails. Higher total cell number was closely associated with faster neutrophil engraftment. Compared with historical controls, neutrophil engraftment was significantly accelerated in more recent studies using small molecules or mesenchymal stromal cells (MSC) co-culture, and in some cases, platelet recovery was also statistically improved. Recent studies using nicotinamide and StemRegenin-1 reported long-term chimerism of the expanded unit. No significant improvement in survival or other transplant-related outcomes was demonstrated for any of the strategies. Ex vivo expansion of UCB can accelerate initial neutrophil engraftment after transplant. More recent studies suggest that long-term engraftment of ex vivo expanded cord blood units is achievable. Results of larger randomized controlled trials are needed to understand the impact on patient outcomes and health care costs.
authors.affiliation: Center for Transfusion Research, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kiernan
authors.affiliation: Center for Transfusion Research, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Pauline
authors.initials: P
authors.lastname: Damien
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Madeline
authors.initials: M
authors.lastname: Monaghan
authors.affiliation: Medical Library Services, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Risa
authors.initials: R
authors.lastname: Shorr
authors.affiliation: Center for Transfusion Research, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Lauralyn
authors.initials: L
authors.lastname: McIntyre
authors.affiliation: Center for Transfusion Research, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dean
authors.initials: D
authors.lastname: Fergusson
authors.affiliation: Center for Transfusion Research, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Tinmouth
authors.affiliation: Center for Transfusion Research, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: daallan@ohri.ca.
authors.forename: David
authors.initials: D
authors.lastname: Allan
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002648:Child; D046528:Chimerism; D002986:Clinical Trials as Topic; D018920:Coculture Techniques; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D015925:Cryopreservation; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006085:Graft Survival; D017048:Health Care Costs; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D016896:Treatment Outcome
chemical_list: D016207:Cytokines
keywords: Hematopoietic stem cell engraftment; Hematopoietic stem cell expansion; Transplantation; Umbilical cord blood