Hijacking the Pathway: Perspectives in the Treatment of Mature T-cell Leukemias

Wahnschaffe, Linus; Herling, Marco

doi:10.1097/hs9.0000000000000573

Cited by 4 publications

(7 citation statements)

References 36 publications

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“…Whether MTX or CP should be given as first line therapy is not clear. To clarify this situation, a phase II randomized trial comparing first-line MTX versus CP ( NCT01976182 ) is ongoing ( 26 ).…”

Section: Case Reportsmentioning

confidence: 99%

“…Considering the pathogenesis of LGL leukemia, various specific inhibitors were evaluated in T-LGLL. Tofacitinib, a JAK3-specific inhibitor, showed in T-LGLL patients an improvement of RA symptoms and a hematological response in 6/9 (67%) cases ( 26 , 41 ). BNZ-1 a multi-cytokine inhibitor that inhibits interleukin (IL)-2, IL-15 and IL-9 signaling showed promising results in reducing cytokine mediated cell survival being investigated in a phase I/II trial ( 42 ).…”

Section: Case Reportsmentioning

confidence: 99%

“…Constitutive activation of STAT3 is often related to STAT3 gain of function mutations in 30-40% of T-LGLL (24,25). STAT5b mutation is less frequent (2%) but highly prevalent in the rare subset of CD4+ T-LGL (1,(26)(27)(28)(29). Therefore, mutations in STAT3 and STAT5b were included in the 2017 WHO classification of LGL disease (3,12).…”

Section: Introductionmentioning

confidence: 99%

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T-Cell Large Granular Lymphocyte Leukemia: An Interdisciplinary Issue?

et al. 2022

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Section: Case Reportsmentioning

confidence: 99%

Section: Case Reportsmentioning

confidence: 99%

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T-Cell Large Granular Lymphocyte Leukemia: An Interdisciplinary Issue?

et al. 2022

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“…It is assumed that prolonged stimulation in this context may cause LGL clonal expansion, associated with the deregulation of several pro- and anti-apoptotic signaling pathways. Recent studies point to the constitutional activation of STAT3, and more rarely of STAT 5b, as a key concept in the etiopathogenesis of LGL [ 6 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

T-large Granular Lymphocytic Leukemia: A Rare Diagnosis in a Young Woman With Fever, Necrotic Skin Lesions and Cytopenias

Ferreira,

Paulo,

Ramos

et al. 2024

Cureus

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T-large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder. The diagnosis is established by identifying an abnormally high number of clonal granular T lymphocytes in the peripheral blood and eventually in the bone marrow, in cases with medullary infiltration. The majority of patients present with symptoms related to neutropenia and this condition may be associated with autoimmune diseases in up to a third of cases. The authors describe the case of a 26-year-old patient admitted with subacute high fever and bullous dermatitis with necrotic lesions with central bullae. Analytically, she presented anemia and leukopenia with severe neutropenia of 200 cells/L. Skin lesions were compatible with ecthyma and the skin biopsy revealed aspects compatible with leukocytoclastic vasculitis. The myelogram and bone biopsy revealed hypoplasia of the myeloid line and a pathological T population of CD8+, TIA-1+ and granzyme B+, which were associated with compatible flow cytometry (CD3+, T-cell receptor (TCR) Alpha-Beta+, CD5+, CD2+, with loss of CD7 antigen expression) established the diagnosis of T-LGLL. The patient had a favorable evolution, with cytopenias almost returning to normal after two months. She began follow-up at a Hematology Reference Center, remaining asymptomatic without specific treatment considering the indolent course of the disease.

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“…Treatment-defining prospective trials are hardly available. For a summary of tested strategies see ( 15 ). Furthermore, there is a great deal of uncertainty regarding the optimal timing of treatment initiation.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Large Granular Lymphocyte Leukemia (LGLL)—A Case Series of Challenging Presentations

Pflug

Littauer

Beverungen³

et al. 2022

Front. Oncol.

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Large granular lymphocyte leukemia (LGLL) represents a rare group of diseases with considerable difficulties in their correct diagnostic workup and therapy. The major challenges lie in their distinction from reactive (including autoimmune) lymphoproliferations. Moreover, monoclonal LGL proliferative diseases are in fact a heterogeneous group of disorders, as recognized by the three subtypes in the current WHO classification. It distinguishes two chronic forms (the focus of this case series), namely T-LGLL and chronic lymphoproliferative disorders of Natural Killer cells (CLPD-NK) as well as aggressive NK-cell leukemia. In the clinical routine, the variable presentations and phenotypes of T-LGLL and CLPD-NK are underappreciated. The relevant differential diagnoses range from benign reactive T-cell expansions to other mature T-cell leukemias to highly aggressive γδ-lymphomas. T-LGLL or CLPD-NK patients suffer from a wide variety of symptoms often including, but not limited to, cytopenias or classical autoimmune phenomena. They receive treatments ranging from mere supportive measures (e.g. antibiotics, growth factors, transfusions) over strategies of immunosuppression up to anti-leukemic therapies. The diagnostic pitfalls range from recognition of the subtle T-cell proliferation, repeated establishment of monoclonality, assignment to a descript immunophenotypic pattern, and interpretations of molecular aberrancies. Here, we report a series of selected cases to represent the spectrum of LGLL. The purpose is to raise awareness among the scientifically or practically interested readers of the wide variety of clinical, immunological, and phenotypic features of the various forms of LGLL, e.g. of T-cell type, including its γδ forms or those of NK-lineage. We highlight the characteristics and courses of four unique cases from two academic centers, including those from a prospective nationwide LGLL registry. Each case of this instructive catalogue serves to transport a key message from the areas of (chronic inflammatory) contexts in which LGLL can arise as well as from the fields of differential diagnostics and of various treatment options. Implications for optimization in these areas are discussed.

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Hijacking the Pathway: Perspectives in the Treatment of Mature T-cell Leukemias

Cited by 4 publications

References 36 publications

T-Cell Large Granular Lymphocyte Leukemia: An Interdisciplinary Issue?

T-Cell Large Granular Lymphocyte Leukemia: An Interdisciplinary Issue?

T-large Granular Lymphocytic Leukemia: A Rare Diagnosis in a Young Woman With Fever, Necrotic Skin Lesions and Cytopenias

Case Report: Large Granular Lymphocyte Leukemia (LGLL)—A Case Series of Challenging Presentations

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