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
- 1Institut Paoli-Calmettes, Marseille, France
- 2Centre Hospitalier Universitaire (CHU) de Montpellier, Montpellier, France
- 3CHU Henri Mondor, Créteil, France
- 4CHU Edouard Herriot, Lyon, France
- 5Institut Gustave Roussy, Villejuif, France
- 6CHU Hôtel-Dieu, Nantes, France
- 7CHU de la Pitié Salpetrière, Paris, France
- 8CHU Huriez, Lille, France
- 9CHU de Toulouse, Toulouse, France
- 10CHU de Nancy, Nancy, France
- 11CHU de Besançon, Besançon, France
- 12CHU de Poitiers, Poitiers, France
- 13CHU d'Angers, Angers, France
- 14CHU de Saint-Etienne, Saint-Etienne, France
- 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.
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.
Keywords:
CD34+ stem cells, chronic GVHD, leukemia, allogeneic myeloablative transplantation
