Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation

Abstract

The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti-inflammatory mediators in plasma samples drawn daily during the conditioning of 20 patients. Soluble tumour necrosis factor alpha receptor I (sTNFRI) increased during the conditioning reflecting the type of conditioning given. Antithymocyte globulin (ATG) was the most potent inducer of sTNFRI (288% increase (median) P=0.002), followed by VP-16 (184%, P=0.03), cyclophosphamide (129%, P=0.03) and total body irradiation (148%, P=0.0005). Administration of i.v. busulfan (Busilvex; BU) was not associated with significant changes in sTNFRI levels. At day 0 (the day of stem cell infusion) the sTNFRI levels were not only elevated compared with baseline (188% increase), P<0.0001), they also correlated with the baseline values (r=0.72, P=0.0003). The levels of tumour necrosis factor, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12 stayed at low levels during the conditioning, except from a transient increase in the levels of IL-6, IL-8, IL-10 and IL- receptor antagonist (IL-Ra) seen after ATG infusion. These findings suggest that further investigation of circulating sTNFRI levels may be of interest in studies of prognostic factors in SCT.