Chemo-immunotherapy with bendamustine hydrochloride (BH) and alemtuzumab (ALZ) in T-prolmphocytic leukemia (T-PLL): A clinico-in-vitro correlative study.

Abstract

e18557 Background: T-PLL is a rare, but chemo-resistant malignancy, associated with a dismal median survival of about 7.5 months.The optimal treatment for T-PLL is still unknown. Preliminary data indicated high induction response rate with the human CD52 antibody, ALZ. The median remission duration of 7 months however, is short. Moreover, use of ALZ is frequently complicated by infectious complications, thereby limiting the prolonged use of ALZ as a single agent. The results with conventional chemotherapy are disappointing. There is an unmet need to define better treatment strategies for T-PLL. Methods: A 55-year-old female with advance T-PLL presenting with leukocytosis, bicytopenia, hepatosplenomegaly and lymphadenopathy was treated with ALZ for 3 cycles with only minor response attained. BH at 90mg/m2 for 2 days was subsequently given and resulted in remarkable response, with normalization of blood counts within a week and reduction in size of tumor masses. As T-PLL cell lines are not commercially available, T-PLL cells (CD4+CD8+) from peripheral blood frozen at diagnosis were enumerated by flow cytometry via staining with AnnexinV and 7AAD after incubation with BH, ALZ and the combination of both agents at various achievable serum concentrations for 2, 6 and 24 hours. Results: ALZ alone did not result in any significant cell death at all concentrations and time-points.Incubation with BH at concentration above 30µg/ml for 24 hours resulted in cell death in a concentration dependent manner. Combination of BH and ALZ resulted in a time and concentration dependent increase in cell death contributed by both apoptosis and necrosis (Table). Conclusions: BH is an active agent in T-PLL and synergizes with ALZ in tumor cell killing. This study provides an important proof of principle for frontline clinical trials exploring this novel chemo-immunotherapy combination in treating T-PLL. Total percentage cell death over control with different concentrations of BH and ALZ at 6 and 24 hours. Agents Total % cell death (mean±SD) 6 hours 24 hours 10 µg/ml BH + 5 µg/ml ALZ 5.2±3.1 8.51±0.5 30 µg/ml BH + 10 µg/ml ALZ 7.3±1.9 28.7±3.6 100 µg/ml BH + 30 µg/ml ALZ 13.4±2.2 57.6±1.1