BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD.

Myelosuppression, graft-versus-host disease (GVHD), and relapse remain major causes of morbidity after stem cell transplantation for relapsed lymphoma. In this phase 1/2 study, we tested the safety and efficacy of escalating doses of bendamustine (70, 90, 110, and 130 mg/m2 per day for 3 days), coupled with our historical fixed doses of fludarabine and rituximab (BFR), as a nonmyeloablative allogeneic conditioning regimen for patients with relapsed lymphoma (n = 41) and chronic lymphocytic leukemia (CLL) (n = 15). Ten patients entered the phase 1 study; none experienced a dose-limiting toxicity. Forty-six additional patients were then treated in the phase 2 study at the maximum dose of 130 mg/m2 per day for 3 days. The proportions of transplants from matched siblings or unrelated donors were 54% and 46%. Remarkably, 55% of patients did not experience severe neutropenia. Forty-nine patients (88%) did not require platelet transfusion. The incidence of acute grade II-IV GVHD was 11%. The 2-year rate of extensive chronic GVHD was 26%. After a median follow-up duration of 26 months (range, 6-50 months), the 2-year overall and progression-free survival rates were 90% and 75%. In conclusion, our new BFR regimen is safe and effective for relapsed CLL and lymphoma patients.