Original Manuscript

Leukemia (2003) 17, 869–875. doi:10.1038/sj.leu.2402909

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

M Mohty1, K Bilger1, E Jourdan2,16, M Kuentz3, M Michallet4, J H Bourhis5, N Milpied6, L Sutton7, J P Jouet8, M Attal9, P Bordigoni10, J Y Cahn11, A Sadoun12, N Ifrah13, D Guyotat14, C Faucher1, N Fegueux2, J Reiffers15, D Maraninchi1 and D Blaise1

  1. 1Institut Paoli-Calmettes, Marseille, France
  2. 2Centre Hospitalier Universitaire (CHU) de Montpellier, Montpellier, France
  3. 3CHU Henri Mondor, Créteil, France
  4. 4CHU Edouard Herriot, Lyon, France
  5. 5Institut Gustave Roussy, Villejuif, France
  6. 6CHU Hôtel-Dieu, Nantes, France
  7. 7CHU de la Pitié Salpetrière, Paris, France
  8. 8CHU Huriez, Lille, France
  9. 9CHU de Toulouse, Toulouse, France
  10. 10CHU de Nancy, Nancy, France
  11. 11CHU de Besançon, Besançon, France
  12. 12CHU de Poitiers, Poitiers, France
  13. 13CHU d'Angers, Angers, France
  14. 14CHU de Saint-Etienne, Saint-Etienne, France
  15. 15CHU de Bordeaux, Bordeaux, France

Correspondence: Dr D Blaise, Unité de Transplantation et de Thérapie Cellulaire (UTTC), Institut Paoli-Calmettes and Université de la Méditerranée, 232 Bd. Ste Marguerite, 13273 Marseille Cedex 09, France. Fax: +33 491 223579

16Current address: Service de Médecine Interne B, CHU de Nimes, Nimes, France

Received 25 November 2002; Accepted 16 January 2003.

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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 times 106/kg), as compared to 62% (95% CI, 48–76%) in patients receiving a 'high' CD34+ cell dose (>8.3 times 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.

Keywords:

CD34+ stem cells, chronic GVHD, leukemia, allogeneic myeloablative transplantation

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