Pathogenesis, Treatment, and Future Directions for Rare T-Cell Leukemias

T-cell large granular lymphocytic leukemia (T-LGLL) and T-cell prolymphocytic leukemia are rare hematologic malignancies. T-LGLL is caused by pro-inflammatory states, such as rheumatoid arthritis and other autoimmune diseases. T-LGLL causes severe neutropenia, anemia, and in more aggressive presentations, bone marrow failure and aplastic anemia. However, there have only been three prospective studies ever conducted in this disease, and no new therapies have been developed for 30 years. There is an urgent need for a thorough understanding of the pathogenesis of T-LGLL, it’s connection to rheumatologic/autoimmune disease states, and novel therapeutics. T-PLL is a rare, highly aggressive T-cell leukemia, that is only curable with allogeneic stem cell transplantation. There are limited therapies available, with alemtuzumab, a CD52-directed monoclonal antibody being the most effective agent. However, for elderly patients, or those with refractory or relapsed T-PLL, there are no effective salvage agents. There is an urgent need to understand the pathogenesis of T-PLL and identify potential targets for novel therapeutics.

There is a lack of understanding of the pathogenesis of rare T-cell leukemias that leads to a lack of therapeutics for these diseases. With this series of articles, we aim to present recent advances in theses leukemias, with a focus on pathogenesis, therapeutic trials, and future therapeutic approaches. Articles types will include primarily original research articles, including basic, translational, and clinical trial research. We likewise welcome some review-type articles on the pathogenesis of T-PLL, and on the overlap of T-LGLL with autoimmune disease/malignant disease.