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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4407-4411.
Prepublished online as a Blood First Edition Paper on September 1, 2005; DOI 10.1182/blood-2005-07-2919.
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Submitted July 21, 2005
Accepted August 14, 2005
Inflammatory cytokines and acute graft-versus-host disease after reduced intensity conditioning allogeneic stem cell transplantation
Mohamad Mohty*, Didier Blaise, Catherine Faucher, Norbert Vey, Reda Bouabdallah, Anne-Marie Stoppa, Frederic Viret, Gwenaelle Gravis, Daniel Olive, and Beatrice Gaugler
Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Marseille, France; Unite de Transplantation et de Therapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille, France; Departement d'Hematologie, Institut Paoli-Calmettes, Marseille, France
Unite de Transplantation et de Therapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille, France; Departement d'Hematologie, Institut Paoli-Calmettes, Marseille, France; INSERM UMR 599, Marseille, France
Unite de Transplantation et de Therapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille, France; Departement d'Hematologie, Institut Paoli-Calmettes, Marseille, France
Departement d'Hematologie, Institut Paoli-Calmettes, Marseille, France
Departement d'Oncologie Medicale, Institut Paoli-Calmettes, Marseille, France
Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Marseille, France; INSERM UMR 599, Marseille, France; Universite de la Mediterranee, Marseille, France
Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Marseille, France; INSERM UMR 599, Marseille, France
* Corresponding author; email: mohtym{at}marseille.fnclcc.fr.
This study investigated the role of inflammatory cytokines in acute graft-vs.-host-disease (aGVHD) incidence and severity in 113 patients who received a reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Among all tested cytokines in the first 3 months after allo-SCT, only IL-12p70 levels in the first month, were significantly associated with grade II-IV aGVHD development (P< .0001). IL-12p70 levels were directly correlated to aGVHD severity grade (P< .0001). Prior to aGVHD onset, blood monocytes, the main precursors pool of IL12p70-secreting dendritic cells, recovered more rapidly, in patients with grade II-IV aGVHD (P=.005). Similarly, at the effectors level, there was a more robust reconstitution of naive CD3+CD4+CD45RA+CD27+ T-cells in patients developing grade II-IV aGVHD (P=.006). In multivariate analysis, IL-12p70 level measured in the first month was the strongest predictive factor for aGVHD development (P< .0001). These findings, reconstituting a Th1 loop, support a model where aGVHD reflects a type 1 alloreaction after RIC allo-SCT.
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