The Prognostic Significance of Autoimmune Cytopenias in Patients with Chronic Lymphocytic Leukemia.

Abstract 2361

Poster Board II-338

Clinical staging systems are the backbone for assessing prognosis in patients with chronic lymphocytic leukemia (CLL). Clinical stages, however, are assigned without taking into consideration the mechanisms of the disease. In this regard, the prognosis of patients with advanced (Binet C, Rai III, IV) stage due to immune cytopenia is controversial. To address the prognosis of patients with CLL in advanced clinical stage due to immune mechanisms, we studied two groups of patients with and without autoimmune cytopenia. The first group consisted of 62 patients (39 men, median age 65 yrs; range 33-89) with advanced stage due to autoimmune cytopenia (stage C “immune”). Autoimmune hemolytic anemia (AIHA) was defined as a hemoglobin level <10g/dL and either a positive direct antiglobulin test (n=37) or indirect signs of hemolysis including a high reticulocyte count, low haptoglobin levels, increased LDH and bilirrubin levels (n=7). Immune thrombocytopenia (ITP) was defined as a platelet count < 100.000/mm³ with normal megakaryocytes in bone marrow or no reticulocytopenia, no enlarged spleen and no chemotherapy within the last month from study entry (n=18). The control group included 96 patients (59 men, median age 68 yrs; range 28-90) with stage C disease with no signs of immune-mediated cytopenia. Demographics, clinical characteristics and duration of follow-up were similar in both groups. When considered from the time of diagnosis, patients with stage C “immune” disease had a significantly better survival than those in stage C due to bone marrow infiltration (median survivals: 89 months vs. 45 months; p=0.04). In contrast, the prognosis of 12 patients who developed immune cytopenia during the course of the disease was not different from that of 42 patients who had progressed to stage C with no evidence of autoimmunity, neither when considered from the time of diagnosis (median survivals: 110 months vs. 101 months; p=0.71) nor from the point at which cytopenia (either autoimmune or infiltrative in origin), was detected (median survivals: 51 months vs. 63 months; p=0.102). When the analysis was restricted to the 62 patients with autoimmune cytopenia, no significant differences in survival were observed according to the time at which the autoimmune disorder was detected, i.e. at diagnosis or during the course of the disease (median survivals: 89 months vs.103 months; p=0.38). Of note, 11 out of the 18 patients with stage C “immune” disease at diagnosis responded to corticosteroids and, as a result, switched to stage A, whereas only 8 out of 53 patients with stage C due to bone marrow infiltration had a similar response to chemotherapy. In summary, this study shows that the outcome of patients with CLL who present with advanced clinical stage differs according to the origin of the cytopenia (i.e., immune vs. infiltrative) and emphasizes the importance of determining the origin of the cytopenia when evaluating patients with CLL and “advanced” clinical stage. These results also make a case for including a stage C “immune” group in the prognostic categorization of patients with CLL.