RESUMEN
Large granular lymphocytic (LGL) leukaemia is a rare chronic lymphoproliferative disorder characterized by an expansion of cytotoxic T or NK cells. Despite a usually indolent evolution, most patients will require a treatment over the course of the disease because of cytopenia or symptomatic associated autoimmune disorders. First-line treatment is based on immunosuppressive agents, namely cyclophosphamide, methotrexate and ciclosporin. However, relapses are frequent, and there is no consensus on the management of relapsed/refractory patients. The implication of the JAK/STAT pathway in the pathogenesis of this disease has prompted our group to propose treatment with ruxolitinib. A series of 21 patients who received this regimen is reported here. Ten patients (47.6%) were refractory to the three main immunosuppressive drugs at the time of ruxolitinib initiation. Ruxolitinib yielded an overall response rate of 86% (n = 18/21), including 3 complete responses and 15 partial responses. With a median follow-up of 9 months, the median response duration was 4 months. One-year event-free survival and 1-year overall survival were 57% and 83% respectively. Mild side effects were observed. Biological parameters, notably neutropenia and anaemia, improved significantly, and complete molecular responses were evidenced. This study supports ruxolitinib as a valid option for the treatment of relapsed/refractory LGL leukaemia.
Asunto(s)
Leucemia Linfocítica Granular Grande , Receptores de Antígenos de Linfocitos T gamma-delta , Neoplasias del Bazo , Anciano , Humanos , Genómica/métodos , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/patología , Leucemia Linfocítica Granular Grande/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Linfoma de Células T/genética , Linfoma de Células T/patología , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Neoplasias del Bazo/genética , Neoplasias del Bazo/patologíaRESUMEN
INTRODUCTION: Large granular lymphocytic (LGL) leukemia is a rare lymphoproliferative disorder characterized by an expansion of clonal T or NK lymphocytes. Neutropenia-related infections represent the main clinical manifestation. Even if the disease follows an indolent course, most patients will ultimately need treatment in their lifetime. Interestingly, LGL leukemia is characterized by a high frequency of autoimmune disorders with rheumatoid arthritis being the most frequent. AREAS COVERED: This review covers the pathophysiology, clinic-biological features and the advances made in the treatment of LGL leukemia. A special focus will be made on the similarities in the pathophysiology of LGL leukemia and the frequently associated rheumatic disorders. EXPERT OPINION: Recent advances in the phenotypic and molecular characterization of LGL clones have uncovered the key role of JAK-STAT signaling in the pathophysiology linking leukemic cells expansion and autoimmunity. The description of the molecular landscape of T- and NK-LGL leukemia and the improved understanding of the associated rheumatic disorders open the way to the development of new targeted therapies effective on both conditions.