title: Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation.
abstract: Delayed engraftment is a major limitation of cord blood transplantation (CBT), due in part to a defect in the cord blood (CB) cells' ability to home to the bone marrow. Because this defect appears related to low levels of fucosylation of cell surface molecules that are responsible for binding to P- and E-selectins constitutively expressed by the marrow microvasculature, and thus for marrow homing, we conducted a first-in-humans clinical trial to correct this deficiency. Patients with high-risk hematologic malignancies received myeloablative therapy followed by transplantation with 2 CB units, one of which was treated ex vivo for 30 minutes with the enzyme fucosyltransferase-VI and guanosine diphosphate fucose to enhance the interaction of CD34(+) stem and early progenitor cells with microvessels. The results of enforced fucosylation for 22 patients enrolled in the trial were then compared with those for 31 historical controls who had undergone double unmanipulated CBT. The median time to neutrophil engraftment was 17 days (range, 12-34 days) compared with 26 days (range, 11-48 days) for controls (P = .0023). Platelet engraftment was also improved: median was 35 days (range, 18-100 days) compared with 45 days (range, 27-120 days) for controls (P = .0520). These findings support ex vivo fucosylation of multipotent CD34(+) CB cells as a clinically feasible means to improve engraftment efficiency in the double CBT setting. The trial is registered to www.clinicaltrials.gov as #NCT01471067.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Rohtesh S
authors.initials: RS
authors.lastname: Mehta
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Katayoun
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authors.lastname: Rezvani
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Patricia
authors.initials: P
authors.lastname: Fox
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Kayo
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Ian
authors.initials: I
authors.lastname: McNiece
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Betul
authors.initials: B
authors.lastname: Oran
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Chitra
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authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Amanda
authors.initials: A
authors.lastname: Olson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Partow
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authors.lastname: Kebriaei
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Indreshpal
authors.initials: I
authors.lastname: Kaur
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Eric
authors.initials: E
authors.lastname: Yvon
authors.affiliation: Department of Medicine-Hematology and Oncology, Case Western Reserve University, Cleveland, OH;
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
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authors.initials: LJ
authors.lastname: Cooper
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Priti
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authors.lastname: Tewari
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Amin
authors.initials: A
authors.lastname: Alousi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Roy B
authors.initials: RB
authors.lastname: Jones
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Qaiser
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authors.lastname: Bashir
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ciurea
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Sairah
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Paolo
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authors.lastname: Anderlini
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Doyle
authors.initials: D
authors.lastname: Bosque
authors.affiliation: Department of Blood and Marrow Transplantation, Children's National Hospital System and The George Washington University, Washington, DC;
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authors.initials: C
authors.lastname: Bollard
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Molldrem
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Julianne
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Michael
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authors.lastname: Thomas
authors.affiliation: Preclinical Research Department, Targazyme Inc., Carlsbad, OH; and.
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authors.affiliation: Preclinical Research Department, Targazyme Inc., Carlsbad, OH; and.
authors.forename: Steve
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authors.lastname: Wolpe
authors.affiliation: The Centre for Stem Cell Research, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center, Houston, TX.
authors.forename: Paul
authors.initials: P
authors.lastname: Simmons
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Simon
authors.initials: S
authors.lastname: Robinson
authors.affiliation: Department of Medicine-Hematology and Oncology, Case Western Reserve University, Cleveland, OH;
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Zweidler-McKay
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, and.
authors.forename: Elizabeth J
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authors.lastname: Shpall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology* / Q000276:immunology; D015331:Cohort Studies; D019040:E-Selectin / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D019007:P-Selectin / Q000378:metabolism; D017713:Platelet Transfusion; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D019040:E-Selectin; D019007:P-Selectin; D005643:Fucose; D005647:Fucosyltransferases