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The aim of this study was to retrospectively analyse clinical characteristics of chronic GVHD (cGVHD) and requirements for immunosuppressive treatment (IST) in patients receiving reduced-intensity stem cell transplantation (RIST). About 29 patients who underwent RIST between September 1999 and April 2003 were evaluable for cGVHD; they were compared to an age-matched cohort of 29 patients who received conventional stem cell transplantation (CST).A total of 26 patients in the RIST group and 24 in the CST group developed cGVHD, which was graded as limited disease in 15 (52%) and 12 (41%) cases, respectively, and as extensive disease in 11 (38%) and 12 (41%) cases, respectively. Kaplan-Meier estimates of the risk of cGVHD at 1 year after transplant were 96 and 82%, respectively (p = 0.4). The median day of onset of cGVHD was 117 (range 93-220) in RIST group and 112 (range 77-225) in CST group. The skin was the most common target organ, involving 22 (84%) patients in the RIST group and 17 (71%) in the CST group. The probability of withdrawal from systemic IST at 3 years was 63 and 52% in the two groups, respectively, (p = 0.7). By multivariate analysis, RIST was the only, independent, prognostic factor for the development of refractory cGVHD (p = 0.01).In conclusion, we did not find major differences between patients receiving RIST and CST respect to timing, clinical characteristics and incidence of cGVHD. Refractory disease was more frequently observed in patients receiving RIST, although the probability of withdrawal from systemic IST was not significantly different between the two groups.