Rituximab in Combination with High-Dose Steroids in Advanced, Refractory Chronic Lymphocytic Leukaemia.

High-dose methlyprednislone (HDMP) is active in refractory chronic lymphocytic leukaemia (CLL), and rituximab, although showing limited efficacy as a single agent, is effective when used in combination with other cytotoxic agents. Early relapse (<12 months) after purine-analogue based treatment poses a difficult management problem as older patients may be unable to tolerate treatment intensification. This retrospective audit examines the outcome in patients with advanced, refractory/relapsed CLL treated with a combination of high-dose steroids and rituximab. Eleven patients with CLL were treated with rituximab (375mg/m²) and high-dose steroids between 2003 and 2007. Ten patients had advanced and/or refractory disease and one patient had severe autoimmune haemolytic anaemia complicating early-stage CLL. Median age was 70 (range 54–82) and there were 7 male and 4 female patients. Nine patients had Binet stage C disease. Six of the 7 patients for whom results were available had germ-line variable heavy chain immunoglobuliun genes. Median number of prior treatments was 2 (range 1–6) with 9 patients having already received a fludarabine based-regimen. Six patients received a combination of rituximab and high-dose methylprednisolone (1gm/m² on days 1–5) and 5 patients received a combination of rituximab and high-dose dexamethasone (40mg daily on days 1–4) and. Cycles were repeated every 28 days and the median number of cycles received was 4 (3–6). Antiviral and anti-PCP prophlaxis with aciclovir and co-trimoxazole was routinely prescribed. Response was assessed according to the NCI working group criteria. There was one complete response (CR) and 7 partial responses (PR). Furthermore, 2 of the patients who achieved a PR were successfully salvaged prior to reduced-intensity allogeneic stem-cell transplant and both remain in complete remission (CR) post-transplant. The other 3 patients had minor responses that did not meet NCI response criteria. Median duration of response was 13 months (6–35), excluding the 2 patients who received allogeneic transplants. Three patients required hospital admission with infective complications during treatment. No other significant toxicity was observed. 3 patients have died, none of whom had attained a PR. In conclusion, we found that rituximab in combination with high-dose steroids is a safe and well-tolerated combination in patients with advanced refractory CLL. One patient achieved a CR and we observed a PR in 7/11 patients. Importantly, 2 of these patients were successfully salvaged prior to reduced-intensity conditioning allogeneic stem-cell transplant and both remain in CR at 4 and 12 months respectively post-transplant.