OBJECTIVE: The aim of our preliminary study was to evaluate the potential role of (18)F-FDG PET-CT in monitoring response to reduced-intensity conditioning (RIC) transplant in a small series of chronic lymphocytic leukemia (CLL) patients and to compare the results with those obtained by standard criteria. METHODS: We retrospectively analyzed 9 consecutive refractory/relapsed CLL patients, who underwent RIC transplant from March 2004 until May 2009. PET-CT was planned at 6-8 months after transplant to assess response and at a mean of 6 months during follow-up. The mean long-term follow-up period was 38 months (range 12-74 months, median 29 months). RESULTS: The first PET-CT showed abnormal (18)F-FDG uptake in five patients, while by standard criteria eight patients showed persistent disease. At the end of follow-up (mean 38 months), all four patients with previously negative scan were still PET negative and in complete remission by standard criteria. All five patients with previously positive scan were still PET positive: one patient died for disease progression and four are alive with disease. CONCLUSIONS: Our preliminary data, although in a small series of CLL patients, suggest that the metabolic findings revealed at first PET-CT after transplant seem to predict the patient outcome and to assess the metabolic disease status earlier than clinical evaluation by standard criteria. PET-CT performed during follow-up may be useful to early detect disease progression.