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Allogeneic transplantation of multiple umbilical cord blood units in adults: role of pretransplant-mixed lymphocyte reaction to predict host-vs-graft rejection

Leukemia volume 22, pages 1786–1790 (2008)Cite this article

Reduced-intensity conditioning (RIC) with conventional adult donor allogeneic graft sources is increasingly utilized for patients deemed unable to tolerate fully myeloablative conditioning due to advanced age and/or comorbidity; with the advantages of lower early treatment-related mortality and faster hematopoietic recovery.1 Use of unrelated allogeneic umbilical cord blood (UCB) grafts in the reduced-intensity setting, however, has been limited due to concerns of possible higher rates of primary graft failure.2, 3 Limited cell dose in a single UCB graft provides sound rationale for consideration of multiple UCB unit transplantation in adult patients. Early experience with two unit UCB infusions has included specified requirements for human leukocyte antigens (HLA) matching between UCB units as well as to the patient.4, 5, 6 In UCB multiunit studies to date, there has been no unit characteristic (cell dose, degree of HLA matching and so on) that predicts donor engraftment of one UCB unit over another.

This exploratory phase I prospective clinical trial was designed to determine if a minimum nucleated cell dose (⩾5 × 107 per kg) provided by infusion of multiple (3–5) unrelated donor UCB units would improve rates and kinetics of allogeneic donor engraftment for adult recipients treated with RIC. This strategy was based on a review of UCB engraftment after myeloablative conditioning7 indicating 100% probability of allogeneic donor engraftment in pediatric recipients receiving single UCB graft cell doses exceeding 5 × 107 cells per kg.

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Acknowledgements

This work was supported by the Abraham J & Phyllis Katz Foundation and Donald J & Ruth Weber Goodman Philanthropic Fund.

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Authors and Affiliations

  1. Department of Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA

    L R Fanning, Y Hegerfeldt, M Lesniewski, M Kozik, M Finney, H M Lazarus & M J Laughlin

  2. Department of Biology, Case Western Reserve University, Cleveland, OH, USA

    L R Fanning

  3. Department of Pathology, Case Western Reserve University, Cleveland, OH, USA

    M Tary-Lehmann, R P Weitzel, H J Meyerson & M J Laughlin

  4. Cleveland Clinic Foundation, Cleveland, OH, USA

    J Maciejewski

  5. Cleveland Cord Blood Center, Cleveland, OH, USA

    P Paul & M J Laughlin

  6. Stem Cell Biology Program, University of Louisville, Louisville, KY, USA

    M Z Ratajczak

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Correspondence to M J Laughlin.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Fanning, L., Hegerfeldt, Y., Tary-Lehmann, M. et al. Allogeneic transplantation of multiple umbilical cord blood units in adults: role of pretransplant-mixed lymphocyte reaction to predict host-vs-graft rejection. Leukemia 22, 1786–1790 (2008). https://doi.org/10.1038/leu.2008.55

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