Low dose alemtuzumab-associated immune thrombocytopenia in chronic lymphocytic leukemia

The occurrence of alemtuzumab-associated immune thrombocytopenia (ITP) have been previously anecdotally reported in chronic lymphocytic leukemia (CLL) patients. Despite ITP is a common autoimmune complication in CLL, occurring in up to 5% of patients, it has never been reported as a significant event complicating alemtuzumab treatment in clinical trials. Recently, it has been reported a new distinctive form of secondary ITP occurring in 6 out of 215 patients with relapsing-remitting multiple sclerosis treated with alemtuzumab at very low-dose within the context of a randomized, controlled phase II trial (Cuker et al, Blood 2011).We investigated the incidence of ITP in a cohort of 64 consecutive patients treated at our center for relapsed/refractory CLL from 2003 to 2010 with low-dose alemtuzumab (Cortelezzi et al, Leukemia 2009). Alemtuzumab was administered at a dose that is one third weekly (30 vs 90 mg) and half cumulative (540 vs 1080 mg) with respect to the conventional schedule. ITP was diagnosed in 3 patients (4.7%) before alemtuzumab treatment during a median observation time of 76 months (range 6-280) and in 9 patients (14.8%) after alemtuzumab, during a median observation time of 30 months (range 2- 93). ITP developed after a median time from alemtuzumab exposure of 12 months (range 1-42). Concomitant hemolytic anemia (Evans syndrome) was observed in one patient. At ITP diagnosis, median platelet count was 11x109/L (range 3-70). Anti-platelet antibodies (Capture P® Method, ImmucorGamma, Norcross GA, USA) were found in 7 of the 8 patients tested. Only two patients showed a clinically significant bleeding and no patient suffered of severe bleeding events. Of the nine patients developing ITP after alemtuzumab, three progressed to a generalized disease after 3, 4 and 13 months respectively, and were treated with chemo-immunotherapy - one patient achieved a partial remission with ITP resolution, while the other two were treatment refractory and died in progression. In the remaining six patients, ITP was not associated to disease progression and they were treated with corticosteroids with or without intravenous immunoglobulins. Five patients achieved a complete remission, while one patient did not respond. Table 1 summarizes the clinical characteristics of the patients.In our cohort of CLL patients treated with alemtuzumab, the incidence of ITP was striking with 5.7 events/100 patient-year, that is almost three times higher than previously reported in CLLIn conclusion, we report for the first time the association between low-dose alemtuzumab treatment and ITP in a prospective cohort of CLL patients. This data suggested an important role of alemtuzumab induced disregulation of T-lymphocytes in the pathogenesis of ITP. As low-dose alemtuzumab have been advocated by our group to be an effective and less toxic treatment for CLL, and a retrospective practice-based study recently supported this notion, we would suggest to maintain a high level of vigilance and to consider routine monitoring for ITP in patients treated with this agent at low-dose.