• Experimental hematology · Nov 2004

    Clinical Trial

    CD8+ T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation.

    • Mohamad Mohty, Sophie Bagattini, Christian Chabannon, Catherine Faucher, Valerie-Jeanne Bardou, Karin Bilger, Norbert Vey, Béatrice Gaugler, Anne-Marie Stoppa, Diane Coso, Patrick Ladaique, Daniel Olive, Patrice Viens, and Didier Blaise.
    • Unité de Transplantation et de Thérapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille, France. mohtym@marseille.fnclcc.fr
    • Exp. Hematol. 2004 Nov 1; 32 (11): 1097-102.

    ObjectiveAcute graft-vs-host disease (aGVHD) remains an important cause of morbidity after reduced-intensity conditioning (RIC) allogeneic transplantation (allo-SCT). It has been shown that antithymocyte globulin (ATG) dose infused during RIC is a major determinant for the likelihood of developing aGVHD. The ATG modulation on aGVHD is likely related to in vivo T-cell depletion.Patients And MethodsWe therefore investigated the relationship between the cellular composition of the allograft and clinical outcome in 57 patients who received allogeneic peripheral blood stem cells from HLA-identical siblings following an ATG-based RIC.ResultsIn a multivariate analysis, the CD8+ T cell dose infused was the only parameter associated with the risk of aGVHD (p=0.031; RR=1.96; 95% CI, 1.1-3.6). When looking at the extremes, patients experiencing grade III-IV aGVHD received a median of 143 x 10(6)/kg CD8+ T cells, while patients without aGVHD received a median of 96 x 10(6)/kg CD8+ T cells (p=0.021). None of the different cell subtypes contained in the allograft was associated with a significant probability of developing chronic GVHD. Patients with grade II aGVHD who received an intermediate dose of CD8+ T cells (median, 111 x 10(6)/kg) had a significantly better overall survival in comparison to patients with grade 0-I or grade III-IV aGVHD (p=0.009).ConclusionIn comparison to myeloablative allo-SCT, these results demonstrate that a cautious monitoring of the number of cells infused, at least in the context of ATG-based RIC, may represent an important predictive indicator of early transplant-related events and outcome after RIC allo-SCT.

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