AB0183 T-CELL LARGE GRANULAR LYMPHOCYTE LEUKEMIA IN PATIENTS WITH FELTY’S SYNDROME

Background:Felty’s syndrome (FS) is a rare subtype of seropositive rheumatoid arthritis (RA) and is characterized by neutropenia and splenomegaly. Some researchers suggest that FS and T-cell large granular leukemia (T-LGLL) may have common pathogenetic relationships [1].Objectives:to characterize the clinical and laboratory manifestations of FS, to evaluate the frequency of T-LGLL and Sjogren’s syndrome (SS) in this group of patients with RA, neutropenia and splenomegaly (pts).Methods:We observed 18 pts with ACCP-positive (100%) and RF-positive (94.5%) RA diagnosed according to ACR 2010 criteria, who also had neutropenia and hepatosplenomegaly. All 18 pts underwent T-LGLL diagnostics using blood smears and phenotyping of peripheral lymphocytes for the presence of granular lymphocytes, determination of T-cell clonality using the rearrangement of the γ-chain of the T-cell receptor of lymphocytes by PCR, histological/immunohistochemical study of bone marrow biopsy specimens for the presence of LGL invasion studies, as well as the study of 4 spleens after splenectomy. SS was diagnosed in 8 out of 18 pts (44.5%) according ACR 2016 criteria.Results:Twelve (66.6%) of 18 pts with RA, neutropenia and splenomegaly were diagnosed with T-LGLL, the patients were divided in 2 groups: FS (6 pts) and RA+T-LGL (12 pts). Pts with FS debuted with arthritis of small hand joints, extremely rarely with extra-articular manifestations, mainly at a young age (36.5±3.9 years), and developed neutropenia after 10 years of RA. Pts with T-LGLL debuted at a younger age (39,5±4,5 and 51,5 + 7,8 years, respectively), had a longer course of RA before the development of neutropenia (14.3±3.3 and 5±1.5 years, respectively, p=0.03), and more often had extra-articular manifestations at the onset of the disease. RA activity did not differ between groups and in most cases was characterized by a mild course of articular syndrome. Though the course of RA+T-LGLL group was characterized by low (50%) and moderate (33%) DAS28-CRP activity and active synovitis in only 41.5% of pts, severe joint deformities (stage III and IV) developed in 58.5% of pts. Pts with T-LGLL showed a higher incidence of hepatomegaly (75% and 16.5%, respectively, p=0.02) and more severe neutropenia (p=0.02). The development of severe leukopenia (<1x109) and massive hepatosplenomegaly was observed only in pts with T-LGLL, which required splenectomy in 4 cases. SS was more often detected in the FS group than in the RA+T-LGLL group (83.5% and 25%, respectively, p = 0.02).Conclusion:Clinical and laboratory manifestations of FS and T-LGLL are extremely close, therefore, pts who are diagnosed with FS should be examined to exclude T-LGLL.References:[1]Liu, Xin, and Thomas P Loughran Jr. “The spectrum of large granular lymphocyte leukemia and Felty’s syndrome.” Current opinion in hematology vol. 18,4 (2011): 254-9. doi:10.1097/MOH.0b013e32834760fb.Disclosure of Interests:None declared

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Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor Vβ-specific monoclonal antibodies

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.1995.tb02271.x ◽

2008 ◽

Vol 101 (1) ◽

pp. 18-24 ◽

Cited By ~ 21

Author(s):

S. J. BOWMAN ◽

M. BHAVNANI ◽

G. C. GEDDES ◽

V. CORRIGALL ◽

A. W. BOYLSTON ◽

...

Keyword(s):

Monoclonal Antibodies ◽

T Cell ◽

T Cell Receptor ◽

Cell Receptor ◽

Large Granular Lymphocyte ◽

Felty's Syndrome ◽

Felty’S Syndrome ◽

T Cell Receptor Vβ ◽

Syndrome Analysis

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Clonal drift demonstrates unexpected dynamics of the T-cell repertoire in T-large granular lymphocyte leukemia

Blood ◽

10.1182/blood-2011-02-338517 ◽

2011 ◽

Vol 118 (16) ◽

pp. 4384-4393 ◽

Cited By ~ 34

Author(s):

Michael J. Clemente ◽

Marcin W. Wlodarski ◽

Hideki Makishima ◽

Aaron D. Viny ◽

Isabell Bretschneider ◽

...

Keyword(s):

Flow Cytometry ◽

T Cell ◽

Cell Receptor ◽

Large Granular Lymphocyte ◽

T Cell Repertoire ◽

Cell Repertoire ◽

Large Granular Lymphocyte Leukemia ◽

Tcr Repertoire ◽

Serial Measurements ◽

Β Chain

AbstractT-cell large granular lymphocyte leukemia (T-LGLL) is characterized by chronic lymphoproliferation of cytotoxic T lymphocytes (CTLs) and is associated with lineage-restricted cytopenias. Introduction of T-cell receptor (TCR) variable β-chain (Vβ) monoclonal antibodies has facilitated identification and enumeration of clonal CTLs by flow cytometry. A highly skewed TCR Vβ repertoire identified by flow cytometry is strongly associated with monoclonal CDR3 regions by quantitative sequencing and positive TCRγ rearrangement assays. Therefore, Vβ expansions can serve as surrogate markers of CTL clonality to assess clonal kinetics in T-LGLL. We analyzed the TCR repertoire in 143 patients, 71 of which were available for serial measurements over 6 to 96 months. Although the majority (38/71, 54%) maintained a consistent monoclonal expansion, many (26/71, 37%) unexpectedly displayed a change in the dominant clone, whereby the original CTL clone contracted and another emerged as demonstrated by Vβ typing. Our results demonstrate that the T-cell repertoire is more dynamic in T-LGLL than recognized previously, illustrating the heterogeneity of disorders under this categorization.

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The case of T-cell large granular lyphocyte leukemia presented as transfusion dependent anemia with sustained response to cyclosporine a therapy: Case report

Medicinski pregled ◽

10.2298/mpns1612376z ◽

2016 ◽

Vol 69 (11-12) ◽

pp. 376-378 ◽

Cited By ~ 1

Author(s):

Vanja Zeremski ◽

Aleksandar Savic ◽

Vesna Cemerikic-Martinovic ◽

Ivana Milosevic ◽

Marina Dragicevic ◽

...

Keyword(s):

Case Report ◽

T Cell ◽

Cell Receptor ◽

Large Granular Lymphocyte ◽

Large Granular Lymphocytes ◽

Large Granular Lymphocyte Leukemia ◽

T Cell Receptor Genes ◽

Cyclosporine Therapy ◽

Dose Oral ◽

Granular Lymphocytes

Case report. A 41-year-old man presented with anemia, lymphocytosis and splenomegaly. T-cell large granular lymphocyte leukemia was diagnosed based on lymphocytosis of T-cell large granular lymphocytes, characteristic immunophenotype (CD3+, CD8+, CD16+, CD57+) of the lymphocytes and clonally rearranged T-cell receptor genes. Therapy indication was transfusion-dependent anemia. Initial cyclosporine therapy and low-dose oral methotrexate failed to control anemia and lymphocytosis. Yet, a complete clinical and hematological response (without molecular remission) was achieved and sustained when cyclosporine was reintroduced into the therapy. Conclusion. Our case confirms that cyclosporine therapy is effective in treating T-cell large granular lymphocyte leukemia and suggests that indefinite treatment may not be needed to maintain the response.

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Comparison of somatic STAT3 and STAT5b gene mutations between Felty's syndrome and T-cell large granular lymphocytic leukemia with rheumatoid arthritis

10.21203/rs.3.rs-64791/v1 ◽

2020 ◽

Author(s):

Vadim R. Gorodetskiy ◽

Yulia V. Sidorova ◽

Natalia A. Kupryshina ◽

Vladimir I. Vasilyev ◽

Natalya A. Probatova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

Somatic Mutations ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Felty's Syndrome ◽

Large Granular Lymphocytic Leukemia ◽

Felty’S Syndrome ◽

T Cell Clonality ◽

Cell Clonality

Abstract Objectives Approximately 15% of patients with T-cell large granular lymphocytic leukemia (T-LGLL) have rheumatoid arthritis (RA). RA-associated T-LGLL with low large granular lymphocyte counts (aleukemic presentation) and Felty's syndrome (FS) have indistinguishable clinical presentations. These disorders are distinguished by T-cell clonality which is observed in T-LGLL but not in FS. Activating somatic mutations in the signal transducer and activator of transcription 3 (STAT3) and 5 (STAT5b) genes are involved in T-LGLL pathogenesis; however, the prevalence of these mutations in FS is unknown.Methods Based on the rearrangements of T-cell receptor (TCR) gamma and beta genes according to the BIOMED-2 protocol, we examined T-cell clonality in 81 patients with RA and unexplained neutropenia. We stratified these patients by the presence or absence of T-cell clonality, respectively, into 2 groups: RA-associated T-LGLL (56 patients) and FS (25 patients). Allele-specific TaqMan Real-Time polymerase chain reaction assay was employed to detect point somatic mutations in STAT3 and STAT5b genes in each group.Results Mutations of the STAT3 gene were detected in none of the 24 cases of FS and in 22 of 56 cases of RA-associated T-LGLL (39%) (p < 0.001). No mutation of the STAT5b gene was detected in any of the patients in each group.Conclusions Although further data are needed, our results suggest that activating somatic mutations in STAT3 and STAT5b genes are not involved in the pathogenesis of FS.

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