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1.
Ann Hematol ; 103(1): 133-140, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37731148

RESUMO

T-large granular lymphocytes (T-LGL) characterized by dim CD5 staining, although not completely understood, have unique roles in the immune system. Expansion of peripheral blood (PB) clonal T-LGL populations is associated with various entities in adults. We have previously demonstrated clonal T-LGL proliferations in pediatric immune dysregulation/inflammatory/proliferative conditions. However, T-LGL populations have not been studied in broader spectrum pathologies. In this study we evaluated sizes and correlates of T-LGL populations in the pediatric and young adult populations with various disease states. Lymphocytes including T-LGL were investigated retrospectively by reviewing PB multiparameter flow cytometric data with various indications over a 4-year period. Associations with clinical, laboratory findings, and T-LGL population sizes were sought. Among 520 cases reviewed, 240 were females and 280 males with a mean age of 9 years (0-33 years); mean T-LGL population constituted 14% (1-67%) in PB T cells. There were significant differences between T-LGL and CD5-bright, regular T cells. T-LGL correlated with CD8 + /DR + (R = 0.570; P < 0.01) and CD8 + /CD11b + (R = 0.597; P < 0.01) expression, indicating activated cytotoxic phenotype. The highest average T-LGL were seen in bone marrow transplant recipients (23.7%), Evans syndrome (23.7%), lymphoma (20.6%), and acute EBV infection (20.4%) cases, all with underlying immune dysregulation pathologies. In pediatric and young adult patients with different clinical conditions, PB T-LGL constitute an average of 14% of the T cells and have a predominantly activated cytotoxic T cell phenotype. Higher relative presence was seen in cases with an immune dysregulation background. These results may serve as a reference for T-LGL research efforts.


Assuntos
Células Matadoras Naturais , Linfócitos T Citotóxicos , Masculino , Feminino , Humanos , Adulto Jovem , Criança , Citometria de Fluxo , Estudos Retrospectivos
2.
Front Med (Lausanne) ; 10: 1238405, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920595

RESUMO

Felty's syndrome was first described in 1924 by the US-American physician Augustus Roi Felty as a triad of rheumatoid arthritis, splenomegaly and leucopenia. Even nearly 100 years later, this rare syndrome is still paralleled by diagnostic and therapeutic challenges and its pathogenesis is incompletely understood. Neutropenia with potentially life-threatening infections is the main problem and several pathomechanisms like Fas-mediated apoptosis, anti-neutrophil antibodies, anti-G-CSF antibodies, neutrophil consumption in the context of NETosis and suppression of granulopoiesis by T-LGLs have been suggested. Felty's syndrome has various differential diagnoses as splenomegaly and cytopenia are common features of different infectious diseases, malignancies and autoimmune disorders. Additionally, benign clonal T-/NK-LGL lymphocytosis is increasingly noticed in Felty's syndrome, which further complicates diagnosis. Today's treatment options are still sparse and are largely based on case reports and small case series. Methotrexate is the mainstay of therapy, followed by rituximab, but there is less evidence for alternatives in the case of adverse reactions or failure of these drugs. This article gives an updated review about Felty's syndrome including its pathogenesis and treatment options.

3.
Front Immunol ; 14: 1087502, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817454

RESUMO

Vaccines against SARS-CoV-2 are the most effective measure against the COVID-19 pandemic. The safety profile of mRNA vaccines in patients with rare diseases has not been assessed systematically in the clinical trials, as these patients were typically excluded. This report describes the occurrence of agranulocytosis within days following the first dose of an mRNA-1273 vaccination against COVID-19 in a previously healthy older adult. The patient was diagnosed with a suspected STAT3 wild-type T-cell large granular lymphocytic leukaemia (T-LGL). Neutropenia was successfully treated with IVIG, glucocorticoids, and G-CSF. In vitro experiments aimed at elucidating the pathways potentially causing the mRNA vaccine-associated neutropenia indicated that the mRNA, but not the adenoviral Ad26.COV2.S vector vaccine, triggered strong IL-6/STAT3 activation in vitro, resulting in excessive T-cell activation and neutrophil degranulation in the patient but not in controls. mRNA-1273 activated TLR-3 suggesting TLR mediated IL-6/STAT3 pathway activation. To complete the primary series of COVID-19 immunization, we used a single dose of Ad26.COV2.S vector vaccine without reoccurrence of neutropenia. The T-LGL clone remained stable during the follow-up of more than 12 months without ongoing therapy. Our data suggest that switching the immunization platform may be a reasonable approach in subjects with rare associated hematologic side effects due to excess STAT3-mediated stimulation following mRNA vaccination. Using in vitro testing before re-administration of a (COVID) vaccine also has relevance for other rare immune events after (mRNA) vaccination.


Assuntos
COVID-19 , Leucemia Linfocítica Granular Grande , Neutropenia , Humanos , Idoso , Vacina de mRNA-1273 contra 2019-nCoV , Ad26COVS1 , Vacinas contra COVID-19 , Interleucina-6 , Pandemias , SARS-CoV-2 , Vacinação , Adenoviridae , Fator de Transcrição STAT3
4.
Platelets ; 34(1): 2144194, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36458562

RESUMO

The association between T-cell large granular lymphocytes (T-LGL) and ITP is uncertain. The aims of this study were to determine the prevalence of T-LGL in patients with ITP and to describe its association with ITP disease severity. We analyzed flow cytometry results for T-LGL (using a threshold of 0.3 x109 or greater cells/L) or positive T-cell receptor clonality in patients with ITP and nonimmune thrombocytopenia. Descriptive statistics were used to characterize the association between T-LGL and ITP, response to ITP treatments (rituximab and splenectomy) and response to T-LGL treatment. Among ITP patients, 14.3% (13/91) had evidence of a T-LGL population compared to 10.3% (3/29) of patients with non-immune thrombocytopenia. ITP patients with T-LGL had lower nadir platelet counts (2 vs. 47 × 109/L) and received more ITP treatments (median 6 vs. 3) than ITP patients without T-LGL. Response to rituximab was observed in 14.3% (1/7) of ITP patients with T-LGL and 54.5% (6/11) without T-LGL. Response to splenectomy was observed in 25% (2/8) with T-LGL and 56.2% (9/16) without T-LGL. Four patients with ITP and T-LGL received treatment for T-LGL with methotrexate; none had an improvement in platelet count levels. T-LGL may appear in patients with ITP, and the meaning of this finding remains unclear; however, for some patients, the presence of abnormal T-LGL may indicate a more severe form of ITP that tends to be less responsive to therapy. In this cohort, treatment of T-LGL with methotrexate did not improve platelet counts in the few patients who were treated.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Metotrexato , Prevalência , Rituximab/uso terapêutico , Linfócitos
5.
Int J Lab Hematol ; 44(6): 1115-1120, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36380468

RESUMO

INTRODUCTION: T-cell clonality testing by T-cell receptor (TCR) gene rearrangement is key to the diagnosis of T-cell lymphoproliferative disorders such as T-cell large granular lymphocytic (T-LGL) leukemia. Benign clonal T-cell expansions, however, are commonly found in patients without identifiable disease, a condition referred to as T-cell clones of uncertain significance (T-CUS). In practice, T-cell clonality testing is performed for a range of reasons and results are often challenging to interpret given the overlap between benign and malignant clonal T-cell proliferations and uncertainties in the management of T-CUS. METHODS: We conducted a 5-year retrospective cohort study of 211 consecutive patients who underwent PCR-based T-cell clonality testing for suspected T-LGL leukemia at our institution to characterize the use of T-cell clonality testing and its impact on patient management. RESULTS: Overall, 46.4% (n = 98) of individuals tested had a clonal T-cell population identified. Patients with a monoclonal T-cell population were more likely to be older, have rheumatoid arthritis and have higher lymphocyte counts compared to patients with polyclonal populations. The majority of patients eventually diagnosed and treated for T-LGL leukemia had rheumatoid arthritis and lower neutrophil counts compared to untreated patients with monoclonal T-cell populations. A diagnosis of T-LGL leukemia was made in only a minority of patients (n = 48, 22.7%), and only a small proportion were treated (n = 17, 8.1%). CONCLUSION: Our study suggests that T-cell clonality testing most commonly identifies incidental T-cell clones with only a minority of patients receiving a diagnosis of T-LGL leukemia and fewer requiring active treatment. These finding indicate an opportunity to improve utilization of T-cell clonality testing in clinical practice to better target patients where the results of testing would impact clinical management.


Assuntos
Artrite Reumatoide , Leucemia Linfocítica Granular Grande , Humanos , Artrite Reumatoide/patologia , Células Clonais/patologia , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/patologia , Estudos Retrospectivos , Linfócitos T/patologia
6.
Cureus ; 14(7): e26742, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35967149

RESUMO

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder that can arise from T- or natural killer-cell lineages. It is an indolent disease that typically occurs in the sixth decade of life. Most cases of T-cell LGL leukemia (T-LGL) are associated with autoimmune disorders. Patients with T-LGL are generally asymptomatic; however, they can present with symptoms related to neutropenia, infections, and autoimmune disorders. Here, we report two cases of T-LGL in which the patients presented with liver dysfunction.

7.
Front Oncol ; 12: 858426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574379

RESUMO

T-Cell malignancies are a group of heterogeneous disorders composed of primary cutaneous T-cell lymphomas (CTCLs), peripheral T-cell lymphomas (PTCLs), and T-cell leukemias, including T-cell large granular lymphocytic leukemia (T-LGLL). Cases of patients with combined T-cell malignancies and plasma cell dyscrasias (PCD) are reported in the literature, but these are mostly limited to case reports or small case series with <10 patients. Here, we described the clinical course of 26 patients and report baseline characteristics and clinical outcomes including overall survival (OS), progression-free survival (PFS), and objective response rates (ORRs) in this unique population. There was no survival difference in patients with CTCL or T-LGLL and concomitant PCD when treated with standard therapy directed at the T-cell malignancy when compared to historical controls. However, patients with PTCL and concomitant PCD had significantly inferior outcomes with rapid progression and worse OS and PFS at 1.7 years (p=0.006) and 4.8 months (p=0.08), respectively, when compared to historical controls for patients with PTCL, although the limited number of patients included in this analysis precludes drawing definitive conclusions. Treatment directed at the T-cell malignancy resulted in the eradication of the PCD clone in multiple patients (15.4%) including one with multiple myeloma (MM) who experienced a complete response after starting therapy directed at the T-cell malignancy. For patients with T-cell malignancies and concomitant PCD, treatment with standard T-cell-directed therapies is recommended based on this analysis with continued follow-up and monitoring of the concomitant PCD. Further studies are needed to definitively elucidate the increased risk of relapse in patients with PTCL and concomitant PCD, and larger, multi-center cohorts are needed to validate these findings across T-cell malignancies and PCDs.

9.
Front Oncol ; 10: 152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133291

RESUMO

Large granular lymphocyte leukemia (LGLL) is a chronic proliferation of clonal cytotoxic lymphocytes, usually presenting with cytopenias and yet lacking a specific therapy. The disease is heterogeneous, including different subsets of patients distinguished by LGL immunophenotype (CD8+ Tαß, CD4+ Tαß, Tγδ, NK) and the clinical course of the disease (indolent/symptomatic/aggressive). Even if the etiology of LGLL remains elusive, evidence is accumulating on the genetic landscape driving and/or sustaining chronic LGL proliferations. The most common gain-of-function mutations identified in LGLL patients are on STAT3 and STAT5b genes, which have been recently recognized as clonal markers and were included in the 2017 WHO classification of the disease. A significant correlation between STAT3 mutations and symptomatic disease has been highlighted. At variance, STAT5b mutations could have a different clinical impact based on the immunophenotype of the mutated clone. In fact, they are regarded as the signature of an aggressive clinical course with a poor prognosis in CD8+ T-LGLL and aggressive NK cell leukemia, while they are devoid of negative prognostic significance in CD4+ T-LGLL and Tγδ LGLL. Knowing the specific distribution of STAT mutations helps identify the discrete mechanisms sustaining LGL proliferations in the corresponding disease subsets. Some patients equipped with wild type STAT genes are characterized by less frequent mutations in different genes, suggesting that other pathogenetic mechanisms are likely to be involved. In this review, we discuss how the LGLL mutational pattern allows a more precise and detailed tumor stratification, suggesting new parameters for better management of the disease and hopefully paving the way for a targeted clinical approach.

10.
Ocul Immunol Inflamm ; 28(7): 1133-1135, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577464

RESUMO

Purpose: To report of a 55-year-old woman suffering from choroidal infiltrates as a first clinical manifestation of T-LGL leukemia. Methods: Retrospective case report. Results: A healthy woman presented with photophobia in both eyes since 1 month. She showed a panuveitis with anterior chamber as well as vitreous cells, creamy-white choroidal lesions in both eyes and a cystoid macular edema in the left eye. Lab testing showed only a moderate lymphocytosis, all other tests, including a pars plana vitrectomy and an anterior chamber tap, were negative. Due to the persistent lymphocytosis, she was referred to the oncologist. A biopsy of the bone marrow revealed T-LGL leukemia. A subsequent biopsy of the choroid showed an infiltration of T-LGL and therefore systemic therapy with cyclophosphamide was started. Conclusions: This is a very rare case describing an involvement of the choroid in T-LGL leukemia.


Assuntos
Neoplasias da Coroide/diagnóstico , Leucemia Linfocítica Granular Grande/diagnóstico , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias da Coroide/tratamento farmacológico , Corantes/administração & dosagem , Ciclofosfamida/uso terapêutico , Feminino , Angiofluoresceinografia , Humanos , Verde de Indocianina/administração & dosagem , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Linfocitose/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica
11.
Stem Cell Investig ; 7: 24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33437844

RESUMO

This is the first report of a complete remission in aggressive T-cell large granular lymphocytic (T-LGL) leukemia after treatment with pentostatin. The aggressive variant of the disease is rare, and traditional therapies include immunosuppressive agents, however, there is no standard consensus for treatment. Cytotoxic chemotherapy has led to remission in a few reported cases. We present this unique case as an alternative treatment for individuals refractory to chemotherapy. A 55-year-old African American male with hypertension, type II diabetes mellitus, hyperlipidemia, and gout presented with symptoms of multiple ecchymosis, fatigue, and weight loss. He was found to have splenomegaly (SM) and significant leukocytosis to 101 k/µL with 30% blasts on peripheral smear. Following bone marrow aspiration and biopsy with flow cytometry, he was diagnosed with aggressive T-LGL leukemia. The chemotherapy regimen hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) was initially chosen based on his clinical presentation but was refractory to treatment. His therapy was changed to alemtuzumab; however, patient tolerated poorly and did not respond. Pentostatin was added to alemtuzumab with improvement in clinical symptoms and laboratory parameters. The patient was transitioned to pentostatin monotherapy and achieved complete remission after 1 month. This report provides support for pentostatin as an effective treatment for patients with aggressive T-cell malignancies refractory to cytotoxic chemotherapy. Pentostatin has previously been studied to treat T-cell prolymphocytic leukemia (T-PLL), hairy cell leukemia, and marginal zone lymphoma. This case suggests an alternative, well-tolerated option that could be considered for initial therapy of aggressive T-LGL leukemia.

12.
Arch Immunol Ther Exp (Warsz) ; 67(4): 225-236, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31147723

RESUMO

We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3-CD56+) and T-cell large granular lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case-control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3-CD56+ and CD8+CD57+ cells and sub-populations of CD3-CD56+ cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94-4.00); p < 0.001] and RIF [mean difference 1.64 (95% CI 0.82-2.45); p < 0.001] than controls. However, the heterogeneity between the different studies was high. The proportion of peripheral blood CD3-CD56+ and CD8+CD57+ cells in the preconception period does not reflect the risk of implantation failure or miscarriage and should not be recommended indicators for the management of RM and RIF. Further prospective large studies are needed to develop a reliable peripheral blood marker of immune deregulation.


Assuntos
Aborto Habitual/imunologia , Células Sanguíneas/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Matadoras Naturais/imunologia , Adolescente , Adulto , Antígeno CD56/metabolismo , Antígenos CD57/metabolismo , Estudos de Casos e Controles , Contagem de Células , Citotoxicidade Imunológica , Implantação do Embrião , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Adulto Jovem
13.
Int J Hematol ; 110(3): 313-321, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250283

RESUMO

T-cell large granular lymphocyte (T-LGL) leukemia is a rare clonal proliferation of cytotoxic lymphocytes rarely described in solid organ transplant (SOT). We reviewed records from 656 kidney transplant recipients in follow-up at our Center from January 1998 to July 2017. In addition, we researched, through PubMed, further reports of T-LGL leukemia in SOT from March 1981 to December 2017. We identified six cases of T-LGL leukemia in our cohort of patients and 10 in the literature. This lymphoproliferative disorder was detected in one combined liver-kidney, one liver and 14-kidney transplant recipients. Median age at presentation was 46.5 years (IQR 39.2-56.9). The disease developed after a median age of 10 years (IQR 4.9-12) from transplantation. Anemia was the most common presentation (62.5%) followed by lymphocytosis (43.7%) and thrombocytopenia (31.2%). Splenomegaly was reported in 43.7% of the patients. Eight patients (50%) who experienced severe symptoms were treated with non-specific immunosuppressive agents. Six of them (75%) had a good outcome, whereas two (25%) remained red blood cell transfusion dependent. No cases progressed to aggressive T-LGL leukemia or died of cancer at the end of follow-up. These results suggest that T-LGL leukemia is a rare but potentially disruptive hematological disorder in the post-transplant period.


Assuntos
Leucemia Linfocítica Granular Grande , Transplante de Órgãos , Transplantados , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Linfocítica Granular Grande/etiologia , Leucemia Linfocítica Granular Grande/mortalidade , Leucemia Linfocítica Granular Grande/terapia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
14.
Am J Clin Pathol ; 151(5): 494-503, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30715093

RESUMO

OBJECTIVES: Flow cytometry immunophenotyping is limited by poor resolution of T-cell clones. A newly described antibody was recently used to distinguish normal peripheral blood T cells from malignant T-cell clones. Here, we evaluate this antibody as a new diagnostic tool for detecting T-cell clonality in mature peripheral T-cell lymphomas. METHODS: Immunostaining for the T-cell receptor ß chain constant region 1 (TRBC1) along with routine T-cell markers was performed on 51 peripheral blood and two bone marrow samples submitted to the flow cytometry laboratory for suspected T-cell malignancy. RESULTS: TRBC immunophenotyping identified malignant T-cell clones with 97% sensitivity and 91% specificity. Findings correlated with molecular T-cell clonality testing. In cases with equivocal molecular results, TRBC1 immunophenotyping provided additional diagnostic information. CONCLUSIONS: TRBC1 flow cytometric immunophenotyping is a robust and inexpensive method for identifying T-cell clonality that could easily be incorporated into routine flow cytometric practice.


Assuntos
Citometria de Fluxo/métodos , Linfoma de Células T Periférico/diagnóstico , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunofenotipagem , Linfoma de Células T Periférico/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/análise , Valores de Referência
15.
Leuk Lymphoma ; 60(7): 1685-1692, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30652530

RESUMO

Rituximab is known to affect T cell immune responses. We and others have reported expansions of T large granular lymphocytes (T-LGLs) in lymphoma patients after Rituximab. We report here the immunogenetic profiling of the T cell receptor (TR) gene repertoire in 14 patients who received Rituximab post allo-HCT and explore clinicobiological correlations. All experienced antigenic triggers, CMV, EBV re-activation and chronic GvHD and had been treated with Rituximab. Skewing of TRBV genes was observed: 3 TRBV genes accounted for half of the repertoire. Oligoclonal pattern with expanded clonotypes was common. Patients with oligoclonality exhibited frequently cGvHD. Longitudinal samples in one revealed distinct clonotypes, suggesting clonal drift. T-LGL leukemia of donor origin with mixed chimerism eventually developed. In conclusion, we report development of oligoclonal T-LGLs after Rituximab post allo-HCT, alluding to antigen selection. Persistence of this phenomenon likely reflects strong antigenic stimulation by viruses and/or cGVHD aggravated by Rituximab.


Assuntos
Evolução Clonal , Rearranjo Gênico do Linfócito T/imunologia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Linfocítica Granular Grande/patologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Rituximab/efeitos adversos , Adolescente , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Seguimentos , Rearranjo Gênico do Linfócito T/genética , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/terapia , Humanos , Leucemia Linfocítica Granular Grande/induzido quimicamente , Leucemia Linfocítica Granular Grande/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Ativação Viral/efeitos dos fármacos , Adulto Jovem
16.
Cancer Sci ; 109(4): 926-933, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29417693

RESUMO

In recent years, it has become clear that members of the signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. The STAT family consists of seven genes, STAT1-4, STAT5A, STAT5B and STAT6, that are involved in regulating cellular proliferation, apoptosis, angiogenesis and the immune system response. Constitutive activation of STAT3, via mutational changes, is important in oncogenesis in both solid and hematopoietic cancers. In the case of hematopoietic neoplasms, STAT3 driver mutations have been described in T-cell large granular lymphocytic (T-LGL) leukemia and chronic natural killer lymphoproliferative disorders (CLPD-NK) and are seen in 30%-40% of T-LGL leukemia patients. STAT5B is also mutated in T-LGL leukemia and CLPD-NK, but in a much smaller proportion. Here we review past and current research on STAT genes in hematopoietic and solid cancers with emphasis on STAT3 and STAT5B and their roles in the pathogenesis of hematopoietic malignancies, particularly T-LGL leukemia and CLPD-NK.


Assuntos
Carcinogênese/genética , Neoplasias Hematológicas/genética , Leucemia Linfocítica Granular Grande/genética , Mutação/genética , Fatores de Transcrição STAT/genética , Animais , Humanos
17.
Am J Clin Pathol ; 149(2): 164-171, 2018 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-29365010

RESUMO

OBJECTIVE: T-cell large granular lymphocytic (T-LGL) leukemia is associated with B-cell lymphomas (BCLs), especially small BCLs. We aimed to explore and expand upon its association with BCLs. METHODS: We retrospectively studied clinicopathologic features of T-LGL leukemia patients with coexisting BCL from January 2001 to December 2016. RESULTS: Among 432 patients with T-LGL leukemia, 22 (5.1%) had an associated B-cell non-Hodgkin lymphoma. Thirteen (59%) patients had large and nine (41%) had small BCL. T-LGL leukemia occurred synchronously with BCL in five, preceded BCL in three, and followed BCL in 14 patients. Anemia was the most common cytopenia (68%). Only one patient had a history of rheumatoid arthritis. CONCLUSION: To our knowledge, this is the first multicenter study looking at the spectrum and incidence of BCLs in patients with T-LGL leukemia and highlights its association with large BCLs (3% of T-LGL leukemias).


Assuntos
Medula Óssea/patologia , Leucemia Linfocítica Granular Grande/patologia , Linfoma de Células B/patologia , Neoplasias Primárias Múltiplas/patologia , Idoso , Feminino , Humanos , Incidência , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/epidemiologia , Linfoma de Células B/diagnóstico , Linfoma de Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
19.
BMC Infect Dis ; 17(1): 797, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29281994

RESUMO

BACKGROUND: Invasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients. CASE PRESENTATION: We report a case of a 53 year old patient with T-LGL, Immune-Thrombocytopenia (ITP) and combined antibody deficiency, who presented with fever and reduced general condition. The patient revealed a complicated infection involving the lungs and later the brain, with the presentation of vomiting and seizures. Broad microbiological testing of blood-, lung- and cerebrospinal fluid samples was inconclusive. In the absence of mycological proof, Aspergillus infection was confirmed by pathological examination of a brain specimen and finally successfully treated with liposomal amphotericin B and voriconazole, adopting a long-term treatment scheme. CONCLUSIONS: Beyond typical problems in the clinical practice involving fungal infections and hematologic malignancies, this case of invasive aspergillosis in a patient with T-LGL illustrates caveats in diagnosis, therapy and follow-up. Our data support careful ambulatory monitoring for patients with T-LGL, even in the absence of neutropenia. Especially those patients with combined hematologic malignancies and immune defects are at risk. Long-term treatment adhesion for 12 months with sufficient drug levels was necessary for sustained clearance from infection.


Assuntos
Aspergilose/diagnóstico , Encéfalo/patologia , Leucemia Linfocítica Granular Grande/diagnóstico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Encéfalo/diagnóstico por imagem , Encéfalo/microbiologia , Humanos , Leucemia Linfocítica Granular Grande/complicações , Pulmão/microbiologia , Pulmão/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Voriconazol/uso terapêutico
20.
Intern Med ; 56(14): 1759-1769, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28717070

RESUMO

Large granular lymphocytes (LGLs) are large lymphocytes with azurophilic granules in their cytoplasm. LGLs are either natural killer (NK) cells or T lymphocytes. Expansions of the LGLs in the peripheral blood are seen in various conditions, including three clonal disorders: T-cell LGL (T-LGL) leukemia, chronic lymphoproliferative disorders of NK cells (CLPD-NK), and aggressive NK-cell leukemia (ANKL). However, the monoclonal and polyclonal expansion of LGLs has been associated with many other conditions. The present article describes these LGL disorders, with special emphasis on the clinical features, pathogenesis, and treatments of the three above-mentioned clonal disorders.


Assuntos
Células Matadoras Naturais/patologia , Leucemia Linfocítica Granular Grande/patologia , Leucemia Linfocítica Granular Grande/terapia , Adulto , Humanos , Leucemia Linfocítica Granular Grande/diagnóstico , Contagem de Linfócitos , Masculino
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