title: Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft.
abstract: Clinical application of umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by low CD34+ cell dose, increased risk of graft failure, and slow hematopoietic recovery. While the cell dose limitation is partially mitigated by using two UCB units, larger-dosed single units would be preferable. We have evaluated the feasibility and safety of StemRegenin-1 (SR-1), an aryl hydrocarbon receptor antagonist that expands CD34+ cells, by placing one of the two units in expansion culture. SR-1 produced a 330-fold increase in CD34+ cells and led to engraftment in 17/17 patients at a median of 15 days for neutrophils and 49 days for platelets, significantly faster than in patients treated with unmanipulated UCB. Taken together, the marked expansion, absence of graft failure, and enhanced hematopoietic recovery support testing of SR-1 expansion as a stand-alone graft and suggest it may ameliorate a limitation of UCB transplant.
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA; Molecular and Cellular Therapeutics Facility, University of Minnesota, Minneapolis, MN 55108, USA. Electronic address: wagne002@umn.edu.
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Claudio G
authors.initials: CG
authors.lastname: Brunstein
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Boitano
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.affiliation: Molecular and Cellular Therapeutics Facility, University of Minnesota, Minneapolis, MN 55108, USA.
authors.forename: David
authors.initials: D
authors.lastname: McKenna
authors.affiliation: Molecular and Cellular Therapeutics Facility, University of Minnesota, Minneapolis, MN 55108, USA.
authors.forename: Darin
authors.initials: D
authors.lastname: Sumstad
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Chap
authors.initials: C
authors.lastname: Le
authors.affiliation: Novartis Institutes for BioMedical Research, Basel 4000, Switzerland.
authors.forename: Julie
authors.initials: J
authors.lastname: Jones
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cooke
authors.affiliation: Novartis Institutes for BioMedical Research, Basel 4000, Switzerland.
authors.forename: Conrad C
authors.initials: CC
authors.lastname: Bleul
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology; D002478:Cells, Cultured; D002648:Child; D036101:Cord Blood Stem Cell Transplantation; D015925:Cryopreservation; D005312:Fetal Blood / Q000166:cytology*; D006085:Graft Survival; D006680:HLA Antigens / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D011687:Purines / Q000737:chemistry*; D013601:T-Lymphocytes / Q000166:cytology; D016615:Telomere / Q000648:ultrastructure; D019172:Transplantation Conditioning; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D006680:HLA Antigens; D011687:Purines; C552240:StemRegenin 1