Graft versus host disease (GvHD) is the most prominent cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (Allo-HCT). Extracorporeal photoimmunotherapy (ECP) is an alternative therapeutic modality in steroid and/or cyclosporin-A refractory GvHD developing after Allo-HCT. The aim of this study was to evaluate whether there was any relation between serum TNF-a levels and the response to ECP in patients with steroid refractory of extensive chronic GvHD. Between March 2001 and August 2003, seven patients (male: 1, female: 6) had ECP for treatment of steroid refractory extensive chronic GvHD. Five age and gender matched healthy volunteers were included in this study as the control group. The age of the patients ranged from 18 to 49 years. All patients were allografted from HLA-identical sibling donors. The median number of ECP sessions was 10 (8-36), consisting of two sequential cycles monthly. For measurement of serum TNF-a levels, blood samples were obtained both prior to ECP (basal) and after the first and second in all patients and in five patients after the 10th session. Serum TNF-a levels (Quantakine HS, R&D system, UK) were measured in peripheral venous blood samples by an ELISA method. ECP was given at a median of 5.8 months (1-14 months) after allo-HCT. No complications were seen during or after the ECP procedures. The median time of an ECP session was 183 minutes. The median volume of Uvadex used per session was 4.40 ml (3.61-5.61). The basal mean level of TNF-a was higher in patients than in the control group (2.47+/-0.83 pg/ml vs. 1.75+/-0.06, p=0.05). The mean TNF-a levels decreased from 2.47+/-0.83 pg/ml to 1.77+/-0.93 pg/ml after the initial session (p=0.045) and from 2.32+/-0.92 pg/ml to 1.69+/-0.93 pg/ml after the second day (p=0.015). After completion of the ECP sessions, extensive chronic GvHD recovered in only three patients. In three clinically responsive patients, the TNF-a levels were significantly reduced after both the second and tenth sessions. In contrast, in two patients not responding to ECP therapy, TNF-a levels were increased. In order to report whether these changes in TNF levels is an early predictor for evaluation of the efficacy of ECP in extensive chronic GvHD, TNF-a levels should be studied in a larger series.