Immune anemias in patients with chronic lymphocytic leukemia treated with chemoimmunotherapy regimen of fludarabine, cyclophosphamide and rituximab as initial therapy

Abstract

6604 Background: Auto-immune hemolytic anemia (AIHA) has been reported with the use of fludarabine in the treatment of chronic lymphocytic leukemia (CLL). Since rituximab has been used to treat AIHA, it was anicipated that rituximab might reduce the incidence of AIHA when combined with fludarabine to treat CLL. We analyzed the incidence of immune anemias in 300 patients (pts) with CLL treated with fludarabine, cyclophosphamide and rituximab (FCR) as initial therapy. Methods: Diagnosis of AIHA was based on clinical evidence of hemolysis (elevated indirect bilirubin, reticulocyte count, lactate dehydrogenase) combined with positive Coomb’s test and/or low haptoglobin level. Pure red cell aplasia (PRCA) was diagnosed based on absence of erythroid precursors in bone marrow aspirate and/or biopsy. Results: 29 of 300 (9.5%) pts with CLL treated on a single-arm study of FCR showed evidence of immune anemias (age range18 to 86 years,median 62 years; 24 male and 5 female). 24 pts had AIHA, 3 had PRCA and 2 pts had positive Coomb’s test only (hemoglobin>10 gm/dL). Higher beta2-microglobin and bone marrow lymphocyte percentage were associated with higher risk of developing AIHA in multivariate analysis. Immune anemia was present in 9 pts prior to FCR treatment, developed in 15 on FCR and in 5 after completion of FCR (1 month to 4 years later). AIHA was detected after a median of 4 cycles (range 1 to 6) in pts who developed it while on therapy. Coomb’s test was positive in 14 pts and negative in 15. Haptoglobin levels were low in 16, normal in 10 and not measured in 3 pts. Coomb’s test was negative in 14 of 16 pts with AIHA and low haptoglobin levels. 9 pts were treated with oral prednisone. Others treatments included cyclosporine, intravenous immunoglobulin, rituximab and splenectomy. 3 of 9 pts who had AIHA prior to starting FCR had sustained correction of anemia with FCR treatment alone. 2 pts had inadequate response to treatment of immune anemia; 1 of them developed myelodysplastic syndrome. Conclusions: The incidence of immune anemias in pts treated with FCR is comparable to other series. Low haptoglobin levels in appropriate clinical context can help to establish the diagnosis of AIHA in the face of negative Coomb’s test. [Table: see text]