Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation

Uday Popat, Rohtesh S. Mehta, Katayoun Rezvani, Patricia Fox, Kayo Kondo, David Marin, Ian McNiece, Betul Oran, Chitra Hosing, Amanda Olson, Simrit Parmar, Nina Shah, Michael Andreeff, Partow Kebriaei, Indreshpal Kaur, Eric Yvon, Marcos De Lima, Laurence J N Cooper, Priti Tewari, Richard E. ChamplinYago Nieto, Borje S. Andersson, Amin Alousi, Roy B. Jones, Muzaffar H. Qazilbash, Qaiser Bashir, Stefan Ciurea, Sairah Ahmed, Paolo Anderlini, Doyle Bosque, Catherine Bollard, Jeffrey J. Molldrem, Julianne Chen, Gabriela Rondon, Michael Thomas, Leonard Miller, Steve Wolpe, Paul Simmons, Simon Robinson, Patrick A. Zweidler-McKay, Elizabeth J. Shpall

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2885-2892
Number of pages8
JournalBlood
Volume125
Issue number19
DOIs
StatePublished - May 7 2015

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