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Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation

Leukemia volume 17, pages 869–875 (2003)Cite this article

Abstract

Allogeneic peripheral blood stem cell transplantation (PBSCT) has emerged as an alternative to bone marrow transplantation. PBSCT can be associated with a higher incidence of chronic graft-versus-host disease (cGVHD). In this study, we investigated whether there was a correlation between the composition of PBSC grafts (CD34+ and CD3+ cells) and hematological recovery, GVHD, relapse, and relapse-free survival (RFS) after myeloablative HLA-identical sibling PBSCT. The evolution of 100 acute or chronic leukemia patients was analyzed. Neither hematological recovery, acute or cGVHD, nor relapse, was significantly associated with CD3+ cell dose. Increasing CD34+ stem cells was associated with faster neutrophil (P=0.03) and platelet (P=0.007) recovery. Moreover, 47 of the 78 patients evaluable for cGVHD (60%; 95% CI, 49–71%) developed extensive cGVHD. The probability of extensive cGVHD at 4 years was 34% (95% CI, 21–47%) in patients receiving a ‘low’ CD34+ cell dose (<8.3 × 106/kg), as compared to 62% (95% CI, 48–76%) in patients receiving a ‘high’ CD34+ cell dose (>8.3 × 106/kg) (P=0.01). At a median follow-up of 59 months, this has not translated into a difference in relapse. In patients evaluable for cGVHD, RFS was significantly higher in patients receiving a ‘low’ CD34+ cell dose as compared to those receiving a ‘high’ CD34+ cell dose (P=0.04). This difference was mainly because of a significantly higher cGVHD-associated mortality (P=0.01). Efforts to accelerate engraftment by increasing CD34+ cell dose must be counterbalanced with the risk of detrimental cGVHD.

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Acknowledgements

This work was supported in part by a grant from the French Ministry of Health (PHRC 1996) and a grant from the Ligue Nationale de Lutte Contre le Cancer. In addition, Laboratoires Chugai Pharma France (Paris la Défense) provided some support for this study, but did not participate in either the definition or data analysis. Mohamad Mohty was supported by grants from the SFGM-TC, the ‘Fondation de France’ and the ‘Fondation pour la Recherche Médicale’ (Paris, France). We thank D Buckner for critical reading of the manuscript. We thank the clinical research technicians from each participating center for help in data collection. We thank AG Le Coroller (INSERM U379, Marseille) for help with statistical analysis. We also thank the following members of the SFGM-TC for their active participation: JJ Sotto (Grenoble), M Legros (deceased, Clermont-Ferrand), and V Lapierre (Villejuif).

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Author notes

  1. E Jourdan

    Present address: Service de Médecine Interne B, CHU de Nimes, Nimes, France

Authors and Affiliations

  1. Institut Paoli-Calmettes, Marseille, France

    M Mohty, K Bilger, C Faucher, D Maraninchi & D Blaise

  2. Centre Hospitalier Universitaire (CHU) de Montpellier, Montpellier, France

    E Jourdan & N Fegueux

  3. CHU Henri Mondor, Créteil, France

    M Kuentz

  4. CHU Edouard Herriot, Lyon, France

    M Michallet

  5. Institut Gustave Roussy, Villejuif, France

    J H Bourhis

  6. CHU Hôtel-Dieu, Nantes, France

    N Milpied

  7. CHU de la Pitié Salpetrière, Paris, France

    L Sutton

  8. CHU Huriez, Lille, France

    J P Jouet

  9. CHU de Toulouse, Toulouse, France

    M Attal

  10. CHU de Nancy, Nancy, France

    P Bordigoni

  11. CHU de Besançon, Besançon, France

    J Y Cahn

  12. CHU de Poitiers, Poitiers, France

    A Sadoun

  13. CHU d'Angers, Angers, France

    N Ifrah

  14. CHU de Saint-Etienne, Saint-Etienne, France

    D Guyotat

  15. CHU de Bordeaux, Bordeaux, France

    J Reiffers

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Mohty, M., Bilger, K., Jourdan, E. et al. Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation. Leukemia 17, 869–875 (2003). https://doi.org/10.1038/sj.leu.2402909

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