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Cord Blood Stem Cells

Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor

Bone Marrow Transplantation volume 44, pages 213–225 (2009)Cite this article

Abstract

Low severity of GVHD, substantial graft vs tumor (GVT) and slow development of protective immunity are well-documented features of cord blood transplants (CBT). We have evaluated the immune reconstitution of adult recipients of single-unit CBT supported by the coinfusion of third party donor (TPD) mobilized hematopoietic stem cells (MHSC), a procedure—‘dual CB/TPD-MHSC transplant’—that results in early recovery of circulating granulocytes, high rates of CB engraftment and full chimerism. Cumulative recovery of natural killer and B cells at or above the median values of normal controls were 1.0 and 0.76 by the sixth and ninth months. Recovery of T cells was much slower, naive cells lagging behind those of memory and effector (committed) immunophenotypes. Serial analyses of signal joint TCR excision circles showed a general pattern of very low levels by the third month after CBT, followed by recovery to levels persistently similar or higher than those observed before transplantation and in normal controls. Our results are consistent with the clinical observations of substantial GVT effect together with low incidence of serious GVHD and slow development of protective immunity and suggest that thymic function contributes substantially to the recovery of T-cell populations in adults receiving dual CB/TPD-MHSC transplants.

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Acknowledgements

We gratefully acknowledge the cooperation of Dr Dagmar Sigurdardottir (University of Tübingen, Germany), Dr MA Muñoz-Fernández (Laboratory of Immuno-molecular Biology, Hospital General Universitario Gregorio Marañón, Madrid, Spain), Dr M Morado and Dr FH Navarro (Service of Hematology and Hemotherapy, Hospital La Paz, Madrid, Spain) and Dr M Ramirez (Hospital Niño Jesús, Madrid, Spain) who respectively provided the Biotinylated CMV-specific monomers, a plasmid including a fragment of 375 bp of the sjTRECs sequence and the samples from children used in this study. We also gratefully acknowledge the technical assistance of Alicia Pérez and the cooperation of the technical and nursing staff of the Department of Hematology of Hospital Universitario Puerta de Hierro. Dr S Querol (ANRI, London) is acknowledged for the MLC testing of post-transplant and TPD lymphocytes. CB Banks acknowledged by supplying the transplanted CB units include: Barcelona (Spain), Dusseldorf (Germany), Madrid (Spain), New York (US), Milan (Italy), London (UK), Valencia (Spain), Galicia (Spain), St Louis (US), Bordeaux (France), Bensançon (France) and Arcadia (US). Professor George Delclos (University of Texas, Houston, USA) is gratefully acknowledged for his critical revision of the article. This work is supported by grants from EC (AlloStem IP, contract No 503319), Spanish FIS (PI03/0961 & PI04/2794), Spanish Government (SAF 2002-12793E & SAF 2004/0037E), Comunidad Autónoma de Madrid (SAF 2005-04552), Gabrielle Rich Leukemia Foundation, Vidacord and AlloStem-AirProducts Universidad Autónoma de Madrid Chair.

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Authors and Affiliations

  1. Department of Hematology, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, Spain

    T Martín-Donaire, M Rico, G Bautista, R Gonzalo-Daganzo, C Regidor, E Ojeda, I Sanjuán, R Forés, E Ruiz, I Krsnik, B Navarro, S Gil, E Magro, R Sánchez, N Pérez-Sanz, N Panadero, J A García-Marco, R Cabrera & M N Fernández

  2. Department of Biostatistics, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, Spain

    I Millán

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  1. T Martín-Donaire
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  2. M Rico
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  18. J A García-Marco
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  19. R Cabrera
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Correspondence to M N Fernández.

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Martín-Donaire, T., Rico, M., Bautista, G. et al. Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor. Bone Marrow Transplant 44, 213–225 (2009). https://doi.org/10.1038/bmt.2009.15

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