The spectrum of large granular lymphocyte leukemia and Feltyʼs syndrome

Abstract

Purpose of review Patients with chronic large granular lymphocyte (LGL) leukemia often have rheumatoid arthritis, neutropenia and splenomegaly, thereby resembling the manifestations observed in patients with Felty’s syndrome (FS), which is a rare complication of rheumatoid arthritis (RA) characterized by neutropenia and splenomegaly. Both entities have similar clinical and laboratory presentation, as well as common genetic determinant HLA-DR4, indicating they may be part of the same disease spectrum. This review paper seeks to discuss the underlying pathogenesis and therapeutic algorithm of RA, neutropenia and splenomegaly in the spectrum of LGL leukemia and Felty’s syndrome. Recent findings We hypothesize that there may be a common pathogenic mechanism between LGL leukemia and typical FS. Phenotypic and functional data have strongly suggested that CD3+ LGL leukemia are antigen-activated. Aberrations in the T cell repertoire with the emergence of oligoclonal/clonal lymphoid populations have been found to play a pivotal role in pathogenesis of rheumatoid arthritis. The biologic properties of the pivotal T cell involved in rheumatoid arthritis pathogenesis are remarkably similar to those in leukemic LGL. Summary RA-associated T-LGL leukemia and articular manifestations of typical Felty’s syndrome are not distinguishable. A common pathogenetic link between LGL leukemia and RA is proposed.

T Cell Large Granular Lymphocyte Leukaemia with Cutaneous Infiltration

“…3 Frequently, LGL leukaemia is related to autoimmune diseases such as Felty's syndrome and has a chronic and indolent course, with a mean survival of 10 years. 4,5 Occasionally, the behaviour of this form of leukaemia can be more aggressive, especially in cases with a natural killer phenotype. 2 Approximately one-third of patients with LGL leukaemia are clinically asymptomatic, with neutropaenia observed in up to 85% of cases.…”

“…[6][7][8] The indolent course of the disease usually permits a 'wait and see' approach, although indications for treatment include recurrent infections, anaemia, symptomatic splenomegaly or severe B symptoms. 5 Immunosuppressants are the first line of treatment, such as methotrexate, cyclosporine, or cyclophosphamide; these monotherapies are effective in almost 50% of patients by correcting cytopaenia without eradicating the leukaemia cells. 9 However, for those with refractory or highly aggressive forms of the disease, CHOP therapy or a similar chemotherapy regimen is recommended.…”

Białaczki z dużych ziarnistych limfocytów T i komórek naturalnej cytotoksyczności

“…Do najczęściej występujących chorób autoimmunizacyjnych u pacjentów z klonalnymi chorobami limfocytów T-LGL należą reumatoidalne zapalenie stawów (RA, rheumatoid arthritis) (25-30%) i zespół Felty'ego (40%) [43][44][45]. Opisano przypadki białaczki T-LGL z towarzyszącym zespołem Evansa, zespołem Sjögrena, zapaleniem tarczycy typu Hashimoto, chorobą Gravesa-Basedowa, zespołem Cushinga, nadczynnością przytarczyc, stwardnieniem rozsianym, wrzodziejącym zapaleniem jelita grubego, łuszczycą oraz nawracającym zapaleniem naczyniówki [1,3,7,16,21].…”

Large granular lymphocyte cells and immune dysregulation diseases – the chicken or the egg?

“…In fact, T-LGL leukemia patients can show all the features that FS patients have, albeit at varying frequencies, thus making the differential diagnosis between LGL leukemia and FS problematic at times. 3 An additional complication to that of the overlapping clinical features is the fact that both conditions share the presence of LGL cells.…”