Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab – incidence and predictors

Abstract

Immune anaemias (IA) [auto-immune haemolytic anaemia (AIHA) and pure red cell aplasia (PRCA)] are complications of chronic lymphocytic leukaemia (CLL). Fludarabine has been associated with AIHA, whereas both rituximab and cyclophosphamide have been used to treat this condition. Combining these agents with fludarabine may reduce the likelihood of AIHA. We report on the incidence, outcome and pretreatment predictors of IA in 300 patients treated with fludarabine, cyclophosphamide and rituximab (FCR). Nineteen patients (6.5%) developed IA [AIHA (5.8%), PRCA (0.7%)] on or after treatment with FCR. Most patients (82.4%) with AIHA had a negative direct antiglobulin test (DAT). Additional markers of haemolysis (indirect hyperbilirubinaemia, reticulocytosis, low haptoglobin and elevated lactate dehydrogenase levels) confirmed the presence of AIHA in these patients. The majority of patients responded to therapies including steroids, ciclosporin, i.v. immunoglobulin, etc. High pretreatment levels of beta-2 microglobulin predicted for development of IA. No haemolytic crisis was observed during FCR therapy in eight patients with AIHA prior to FCR. Thus, the incidence of IA among CLL patients treated with FCR was comparable with historical rates. The diagnosis of AIHA can be considered even if the DAT is negative. Pre-existing AIHA need not preclude front-line FCR therapy.