High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Tomasz Czerw, Myriam Labopin, Christoph Schmid, Jan J Cornelissen, Patrice Chevallier, Didier Blaise, Jürgen Kuball, Stephane Vigouroux, Frédéric Garban, Bruno Lioure, Nathalie Fegueux, Laurence Clement, Anna Sandstedt, Johan Maertens, Gaëlle Guillerm, Dominique Bordessoule, Mohamad Mohty, Arnon Nagler
Oncotarget 2016 May 10, 7 (19): 27255-66
Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.

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