A Preclinical Model of Double- versus Single-Unit Unrelated Cord Blood Transplantation

George E. Georges*, Vladimir Lesnikov, Szczepan W. Baran, Anna Aragon, Marina Lesnikova, Robert Jordan, Ya Ju Laura Yang, Murad Y. Yunusov, Eustacia Zellmer, Shelly Heimfeld, Gopalakrishnan M. Venkataraman, Michael A. Harkey, Scott S. Graves, Rainer Storb, Barry E. Storer, Richard A. Nash

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Cord blood transplantation (CBT) with units containing total nucleated cell (TNC) dose >2.5 × 107/kg is associated with improved engraftment and decreased transplant-related mortality. For many adults no single cord blood units are available that meet the cell dose requirements. We developed a dog model of CBT to evaluate approaches to overcome the problem of low cell dose cord blood units. This study primarily compared double- versus single-unit CBT. Unrelated dogs were bred and cord blood units were harvested. We identified unrelated recipients that were dog leukocyte antigen (DLA)-88 (class I) and DLA-DRB1 (class II) allele-matched with cryopreserved units. Each unit contained ≤1.7 × 107 TNC/kg. Recipients were given 9.2 Gy total-body irradiation (TBI) and DLA-matched unrelated cord blood with postgrafting cyclosporine and mycophenolate mofetil. After double-unit CBT, 5 dogs engrafted and 4 survived long term with 1 dominant engrafting unit and prompt immune reconstitution. In contrast, 0 of 5 dogs given single-unit CBT survived beyond 105 days (P = .03, log-rank test); neutrophil and platelet recovery was delayed (both P = .005) and recipients developed fatal infections. This new large animal model showed that outcomes were improved after double-unit compared to single-unit CBT. After double-unit CBT, the nonengrafted unit facilitates engraftment of the dominant unit.

Original languageEnglish (US)
Pages (from-to)1090-1098
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number8
DOIs
StatePublished - Aug 2010

Keywords

  • Cord blood transplantation
  • Dog model
  • Graft failure
  • Immune reconstitution
  • Unrelated donor

ASJC Scopus subject areas

  • Transplantation
  • Hematology

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