Rituximab Combining with Fresh Frozen Plasma for the Treatment of Patients with Refractory Advanced CLL.

Abstract 3450

Poster Board III-338

Chronic lymphocytic leukaemia (CLL) is characterized by a progressive accumulation of monoclonal B lymphocytes in the bone marrow, lymphatic organs and blood. Even with the use of newer therapies, many patients with CLL develop progressive, treatment-resistant disease. Rituximab (RTX), a monoclonal antibody, targets CD20 on B lymphocytes and widely used in indolent B cell neoplasms. The lower density of CD20 on CLL cells may play a role, however, the causes of the lesser susceptibility of CLL to RTX remain poorly understood. Complement deficiencies have been identified in many CLL patients and appear to be more pronounced in patients with more advanced disease. Since complement mediated cell lysis is one of the major mechanisms of RTX action, we hypothesized that the therapeutic effect of RTX in CLL may be enhanced by the provision of complement through concurrent administration of fresh frozen plasma (FFP). Between August 2008 and April 2009, twelve patients with refractory advanced CLL were enrolled in this open clinical trial. All had been previously treated with fludarabine and two also failed treatment with RTX. The median age patients was 57 years (range, 48-82 years). According to the Binet staging system, 2 patients were in Binet B, 10 patients in Binet C. Florescence in situ hybridization (FISH) studies identified del(13q14) in 8 patients, and 4 patients with del(13q14) as the sole abnormality. Trisomy 12 was found in 3 patients, del(11q22.3) in 2 paitents, del(17p13) in 2 patients, del(6q23) in 1 patient, and IgH translocation in 1 patient, respectively. By flow cytometry, CD38 was positive in 9 patients, and ZAP-70 positive in 8 patients. Immunoglobulin heavy chain variable gene (IgVH) mutational status was detected by multiplex PCR, and six patients had unmutated VH. Two units of FFP followed with RTX 375 mg/m² as a single agent, repeated every 1-2 weeks up to a total of 2-5 cycles. Complete response (CR) was achieved in 4 patients (33.3%), partial remission (PR) in 6 patients (50.0%). A major improvement of clinical signs and symptoms was achieved in all patients. Lymphocyte counts dropped markedly followed by shrinkage of lymph nodes and spleen and improvement of the anaemia and thrombocytopenia. This could be maintained over 9 months (range, 3-11 months) without progression. Toxicity was minimal and the treatment was well tolerated in all cases. It was show that RTX combining with FFP may provide a useful therapeutic option in patients with refractory advanced CLL.