Evans syndrome (ES) is a rare disease characterized by the simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) and/or immune neutropenia. To better describe the characteristics and outcome of ES in adults, a survey was initiated in 2005. The data from 68 patients (60% of them women) fulfilling strict inclusion criteria for ES are reported. The mean age at time of ITP and/or AIHA onset was 52 plus or minus 33 years, both cytopenias occurred simultaneously in 37 cases (54.5%). ES was considered as "primary" in 34 patients (50%) but was associated with an underlying disorder in half of the cases, including mainly systemic lupus, lymphoproliferative disorders, and common variable immunodeficiency. All patients were given corticosteroids, but 50 of them (73%) required at least one "second-line" treatment, including splenectomy(n ‫؍‬ 19) and rituximab (n ‫؍‬ 11). At time of analysis, after a mean follow-up of 4.8 years, only 22 patients (32%) were in remission off treatment; 16 (24%) had died. In elderly patients, the risk of cardiovascular manifestations related to AIHA seems to be higher than the ITP-related risk of severe bleeding. In conclusion, ES is a potentially life-threatening condition that may be associated with other underlying autoimmune or lymphoproliferative disorders. (Blood. 2009;114:3167-3172)

Treatments for immune thrombocytope-nic purpura (ITP) providing durable plate-let responses without continued dosing are limited. Whereas complete responses (CRs) to B-cell depletion in ITP usually last for 1 year in adults, partial responses (PRs) are less durable. Comparable data do not exist for children and 5-year outcomes are unavailable. Patients with ITP treated with rituximab who achieved CRs and PRs (platelets > 150 10 9 /L or 50-150 10 9 /L, respectively) were selected to be assessed for duration of their response; 72 adults whose response lasted at least 1 year and 66 children with response of any duration were included. Patients had baseline platelet counts < 30 10 9 /L; 95% had ITP of > 6 months in duration. Adults and children each had initial overall response rates of 57% and similar 5-year estimates of persisting response (21% and 26%, respectively). Children did not relapse after 2 years from initial treatment whereas adults did. Initial CR and prolonged B-cell depletion predicted sustained responses whereas prior splenectomy, age, sex, and duration of ITP did not. No novel or substantial long-term clinical toxicity was observed. In summary, 21% to 26% of adults and children with chronic ITP treated with standard-dose rituximab maintained a treatment-free response for at least 5 years without major toxicity. These results can inform clinical decision-making. (Blood. 2012;119(25):5989-5995)

IntroductionImmune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts and may be responsible for mucocutaneous bleeding of variable severity. 1 ITP is usually chronic (Ͼ 6 months) in adults and, after this time, the probability of spontaneous remission is low. Standard management is to initiate steroids, anti-Rh 0 (D) immune globulins, and/or intravenous immunoglobulins (IVIgs) for the more severe forms. [2][3][4][5] The response rate is high but most often transient. That the spleen plays a major role in the removal of damaged platelets has long been known and, to date, splenectomy is still considered the "gold standard" treatment in many countries for the management of chronic ITP with platelet counts less than 30 ϫ 10 9 /L, especially when hemorrhagic complications are present. Approximately two thirds of chronic ITP patients who undergo splenectomy achieve lasting responses. 6 As suggested in the guidelines of the American Society of Hematology (ASH) 7 and the British Committee for Standards in Hematology (BCSH), 8 splenectomy should be considered the main second-line therapy for patients who fail to respond durably to first-line therapy, with persistent platelet counts less than 30 ϫ 10 9 /L. However, increasing numbers of patients are reluctant to undergo splenectomy and physicians are hesitant to recommend it. 9,10 In addition, the risk of overwhelming postsplenectomy infections, although rare, is not predictable and represents a major concern. 11-13 Moreover, some authors reported that, despite initial good responses to splenectomy, the risk of late relapse persists during long-term follow-up 14,15 and severe morbidity resulting from surgery is associated with 11% to 30% postoperative complications requiring prolonged hospitalization or readmission. 11,16 For these reasons, an effective and safe alternative to splenectomy would improve management of chronic ITP.Rituximab is a chimeric, humanized monoclonal antibody directed against the CD20 determinant on B cells. It was initially developed for the treatment of malignant lymphoma but has also been used in autoantibody-mediated disorders, such as rheumatoid arthritis, 17 systemic lupus erythematosus, 18 autoimmune hemolytic anemia, 19 or thrombotic thrombocytopenic purpura. 20 Case reports and several uncontrolled studies described its promising results in ITP patients. Arnold et al 21 conducted a systematic review of published reports on rituximab use in adults with chronic ITP. A complete response, usually observed 3 to 8 weeks after the first infusion, was obtained in 46% of patients. The median response duration was 10.5 months (interquartile range [IQR]: 6.3-17.8 months), but long-term For personal use only. on May 10, 2018. by guest www.bloodjournal.org From responses were not mentioned in all published studies. Arnold et al 21 pointed out the heterogeneity of patients' prior rituximab use and particularly their splenectomy status. Moreover, the short follow-up in some reports and the possible bias due to th...