Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival

Objective To investigate the graft-vs-leukemia effect of allogeneic stem cell transplantation after a nonablative conditioning regimen as treatment for patients with chronic lymphocytic leukemia. Patients and Methods Patients were eligible to treatment if they were refractory or recurred after a prior response to fludarabine. Seventeen patients were treated. All patients received a preparative regimen of fludarabine (30 mg/m2 daily for 3 days) and intravenous cyclophosphamide (750 mg/m2 daily for 3 days). Ten patients received rituximab in addition to chemotherapy. The median time from diagnosis to transplant was 67 months. Nine of 17 patients had refractory disease. Results All patients had engraftment of donor cells. Eleven (65%) did not require platelet transfusions. Ten patients with persistent disease underwent immunomanipulation to augment GVL effects including immunosuppression withdrawal and donor lymphocyte infusion with or without rituximab treatment. Seven of these 10 patients had a complete response and 2 had a partial response; 8 of these 9 responders had received rituximab with their immunomanipulation process. The final response was complete remission in 12 and partial remission in 4 patients for an overall response rate of 94%. Overall survival was 100% for patients who received the combined chemo-rituximab conditioning regimen, vs 14% for those who received chemotherapy alone (p = 0.03). Conclusion Our results indicate that a pronounced GVL effect occurs after nonmyeloablative allogeneic hematopoietic transplantation for advanced CLL. This activity might be facilitated by rituximab. Prospective controlled trials are needed to define the role of nonablative allogeneic hematopoietic transplantation for treatment of this disease.