Leucemia de linfocitos grandes granulares como complicación de artritis reumatoide / Large granular lymphocyte leukemia as a complication of rheumatoid arthritis

La leucemia de linfocitos grandes granulares es una entidad poco frecuente, perteneciente al mismo espectro de trastornos que el síndrome de Felty, que puede presentarse en pacientes con artritis reumatoide de larga evolución. Clínicamente se caracteriza por neutropenia persistente e incremento de la susceptibilidad a infecciones bacterianas, asociado a la presencia en sangre periférica y médula ósea de una expansión clonal de linfocitos atípicos con fenotipo de linfocito T citotóxico, o menos frecuentemente de célula NK; y esplenomegalia. Se diagnostica con mayor frecuencia en pacientes con artritis reumatoide seropositiva con importante daño estructural, manifestaciones extraarticulares y valores persistentemente altos de factor reumatoide y VSG, a pesar de poder presentar escasa actividad inflamatoria articular. Presentamos el caso de un varón de 70 años con artritis reumatoide de larga evolución que desarrolló shock séptico secundario a la infección de una prótesis de cadera por Salmonella spp. Presentaba neutropenia persistente, identificándose en sangre periférica y médula ósea una población monoclonal de linfocitos T aberrantes compatibles con leucemia de linfocitos grandes granulares (AU)

Large granular lymphocyte leukemia is a rare entity belonging to same spectrum of diseases than Felty’s syndrome, which might occur in patients with long-standing rheumatoid arthritis. It is clinically characterized by persistent neutropenia and recurrent bacterial infections associated with the presence in both peripheral blood and bone marrow of clonal expansion of atypic lymphocytes with a cytotoxic T cell phenotype, or less frequently an NK-cell phenotype, as well as splenomegaly. It is more frequently diagnosed in seropositive rheumatoid arthritis, with significant structural damage, extra-articular manifestations and persistently elevated values of ESR, despite them havubg low inflammatory joint activity. We report the case of a 70 year old male with a long-standing rheumatoid arthritis, who developed septic shock secondary to prosthetic hip infection by Salmonella spp. He showed persistent neutropenia, and an aberrant monoclonal T cell population was detected in both peripheral blood and bone marrow, consistent with large granular lymphocyte leukemia (AU)

Neutropenia dynamics in a case of T-LGL lymphoproliferation illustrate rapid turnover of granulocyte progenitors.

OBJECTIVES: To elucidate the natural history of T-cell large granular lymphocyte (T-LGL) lymphoproliferation, we followed changes in associated fluctuating neutropenia for 3 years in an untreated patient presenting with the disease. MATERIALS AND METHODS: We report a nonlinear mathematical analysis of irregular neutrophil fluctuation, using iterative data maps, to detect long-term regulation of the neutrophil population. RESULTS: This geometric analysis indicated that variations of this sequence of neutrophil counts followed bounded deterministic dynamics around a fixed low level equilibrium, a situation similar to that previously observed for cultured mouse early bone marrow progenitor cells. CONCLUSION: These findings illustrate how the deleterious effect of T-LGL on neutrophils is balanced, over periods of years, by pulses of compensatory neutrophil production, potentially accounting for the commonly observed prolonged indolent course of the disease.

Never say die: survival signaling in large granular lymphocyte leukemia.

Large granular lymphocyte (LGL) leukemia is a rare disorder of mature cytotoxic T or natural killer cells. Large granular lymphocyte leukemia is characterized by the accumulation of cytotoxic cells in blood and infiltration in the bone marrow, liver, and spleen. Herein, we review clinical features of LGL leukemia. We focus our discussion on known survival signals believed to play a role in the pathogenesis of LGL leukemia and their potential therapeutic implications.

[Large granular lymphocyte leukemia]. / Leucémies à grands lymphocytes granuleux.

Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK). Both subtypes can manifest as indolent or aggressive disorders. T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis. Rheumatoid arthritis and Felty syndrome are frequent. NK-LGL leukemias can be more aggressive. LGL expansion is currently hypothesized to be a virus (Ebstein Barr or human T-cell leukemia viruses) antigen-driven T-cell response that involves disruption of apoptosis. The diagnosis of T-LGL is suggested by flow cytometry and confirmed by T-cell receptor gene rearrangement studies. Clonality is difficult to determine in NK-LGL but use of monoclonal antibodies specific for killer cell immunoglobulin-like receptor (KIR) has improved this process. Treatment is required when T-LGL leukemia is associated with recurrent infections secondary to chronic neutropenia. Long-lasting remission can be obtained with immunosuppressive treatments such as methotrexate, cyclophosphamide, and cyclosporine A. NK-LGL leukemias may be more aggressive and refractory to conventional therapy.