Castleman disease (CD) is an uncommon non-clonal lymphoproliferative disorder with unknown etiology.No standard therapy is recommended for relapsed/refractory CD patients,thus requiring development of novel experimental approaches.Our cohort of three adult patients with multicentric CD (MCD) were treated with refractory to traditional chemotherapy ienalidomide-containing regimens (10-25 mg lenalidomide perorally administered on days 1-21 in 28-day cycle) as second-to fourth-line treatment.Partial remission was achieved in first plasma-cell CD patient,who relapsed seven months after autologous hematopoietic stem cell transplantation and then failed to respond to four cycles of chemotherapy.Partial remission was obtained in second patient with CD and polyneuropathy,organomegaly,endocrinopathy,monoclonal gammopathy,and skin changes syndrome.Third case showed complete remission with complete disappearance of pleural effusion and ascites and normalization of platelet count.To conclude,encouraging clinical responses were achieved in cohort of three patients with lenalidomide-based regimen,though long-term efficacy remains to be observed.We propose further investigation of therapeutic potential of this drug in treating MCD.