In the course of active, progressive chronic lymphocytic leukemia (CLL), patients have infiltration of peripheral lymphoid tissue and bone marrow with the malignant, monoclonal B cells coexpressing CD5, CD19 and CD23. This is manifest as lymphocytosis, progressive lymphadenopathy and hepatosplenomegaly, and can be associated with progressive neutropenia, anemia and thrombocytopenia. Up to 25% of patients with CLL, including those with stable disease, develop secondary autoimmune disorders, which can confound cytopenias, complicate the course of their CLL, compromise their quality of life, and in some cases can be fatal. 1 The most common among autoimmune disorders in CLL are autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP) and pure red cell aplasia (PRCA). 2 Indeed, CLL is one of the most common secondary causes of ITP. 3 Historically, it was hypothesized that rapid splenic and hepatic clearance of autoantibody-loaded platelets from the circulation was the primary mechanism for decreased platelet count in ITP. 4 However, recent studies showed that impaired platelet production also contributes to the pathogenesis of ITP. 5 Consistent with these findings, two second-line thrombopoietin receptor (TPO-R) agonists, romiplostim (Nplate, Amgen, Thousand Oaks, CA, USA) and eltrombopag (Promacta, GlaxoSmithKline, Research Triangle Park, NC USA), 6 showed remarkable efficacy in patients with primary ITP. 7, 8 As these trials excluded patients with secondary ITP, the activity of these new drugs in CLL-associated ITP has not been reported. Thus, we present two patients with CLL and secondary ITP who responded to eltrombopag. We identified two patients followed at MD Anderson Cancer Center with CLL and ITP who received the TPO-R agonist eltrombopag (Table 1). A third patient was identified who received eltrombopag, but did not respond. Patient 1 was a 74-year-old female diagnosed with Rai stage 0 CLL in December 1995. She received multiple previous treatment regimens for her CLL, and then developed severe thrombocytopenia in May 2009, 5 months after her third course of combined oxaliplatin, fludarabine, cytarabine and rituximab (OFAR). She was noted to have 17p del in 72% of leukemia cells by fluorescence in situ hybridization (FISH), which is a high-risk feature in CLL. Her platelet count dropped from 89 x103 to 1x 103/μl and she received infrequent platelet transfusions for minor bleeding without improvement in platelet counts. Patient 2 was a 49-year-old male who presented in October 2004 with thrombocytopenia and was concurrently diagnosed with CLL and ITP. He was initially treated with prednisone for his ITP, then with one course of fludarabine with cyclophosphamide and then with single-agent rituximab. Following this, in December 2004, his CLL was in partial remission with residual CLL in his marrow, and his platelets were stable at approximately 100x103/μl. FISH analysis of leukemia cells showed 11q deletion in 16.5% of cells. Subsequently, despite stable CLL by other parameters, over several months his platelet count dropped to 30x 103/μl when treatment for ITP was considered.