RESUMO
Group 5 pulmonary hypertension (PH) encompasses diverse diseases, with a few cases linking it to T-cell large granular lymphocytic (LGL) leukemia. We report a case of a 76-year-old woman, diagnosed with LGL leukemia and concomitant PH, treated with oral triple pulmonary arterial hypertension (PAH) therapy. She initially presented with dyspnea on exertion; evaluation revealed severe precapillary PH. Implementing cyclophosphamide for leukemia along with tadalafil and macitentan for PH led to sustained symptomatic and hemodynamic improvement for over 3 years. At that time, deterioration in PH prompted the addition of selexipag, resulting in sustained clinical improvement for an additional 5 years. This case exemplifies the potential for sustained benefits of PAH therapy in leukemia-associated PH and highlights the need for continued research on the mechanistic relationship between LGL leukemia and PH, with the hope of identifying new management strategies.
Assuntos
Hipertensão Pulmonar , Leucemia Linfocítica Granular Grande , Humanos , Idoso , Feminino , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/diagnóstico , Hemodinâmica/fisiologia , Tadalafila/uso terapêutico , Ciclofosfamida/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêuticoAssuntos
Leucemia Linfocítica Granular Grande , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/patologia , Masculino , Anemia Hemolítica/etiologia , Anemia Hemolítica/patologia , Anemia Hemolítica/complicações , Idoso , Feminino , Pessoa de Meia-Idade , Anemia/etiologia , Anemia/complicaçõesRESUMO
Acquired pure red cell aplasia (PRCA) is a rare syndrome characterized by normocytic normochromic anemia with severe reticulocytopenia and absence of erythroid precursors in the bone marrow. For refractory PRCA patients, the low response rate and high toxicity of alternative therapies pose a great challenge. T-cell large granular lymphocyte (T-LGL) leukemia is one of the most common conditions in secondary PRCA and also the most difficult form to manage with an inferior treatment response to other secondary PRCA forms. T-LGL leukemia exhibits sustained activation of the intracellular JAK-STAT signaling pathway. We herein report a case of PRCA associated with T-LGL leukemia that had been refractory to multiple lines of therapies and was successfully treated by ruxolitinib. The patient achieved complete remission and tolerated ruxolitinib well without occurrence of neutropenia or thrombocytopenia. This preliminary finding favors ruxolitinib as a potential salvage therapy for refractory PRCA associated with T-LGL leukemia.
Assuntos
Leucemia Linfocítica Granular Grande , Nitrilas , Pirazóis , Pirimidinas , Aplasia Pura de Série Vermelha , Humanos , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Aplasia Pura de Série Vermelha/tratamento farmacológico , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Leucemia Linfocítica Granular Grande/complicações , Masculino , Pessoa de Meia-Idade , Idoso , Indução de Remissão , Terapia de SalvaçãoRESUMO
Large granular lymphocyte leukemia (LGLL) is a chronic lymphoproliferative disorder characterized by the proliferation of T or NK cytotoxic cells in the peripheral blood, the spleen and the bone marrow. Neutropenia leading to recurrent infections represents the main manifestation of LGLL. One specificity of LGLL is its frequent association with auto-immune disorders, among them first and foremost rheumatoid arthritis, and other hematologic diseases, including pure red cell aplasia and bone marrow failure. The large spectrum of manifestations and the classical indolent course contribute to the diagnosis difficulties and the frequency of underdiagnosed cases. Of importance, the dysimmune manifestations disappear with the treatment of LGLL as the blood cell counts normalize, giving a strong argument for a pathological link between the two entities. The therapeutic challenge results from the high rate of relapses following the first line of immunosuppressive drugs. New targeted agents, some of which are currently approved in autoimmune diseases, appear to be relevant therapeutic strategies to treat LGLL, by targeting key activated pathways involved in the pathogenesis of the disease, including JAK-STAT signaling.
Assuntos
Antineoplásicos , Artrite Reumatoide , Leucemia Linfocítica Granular Grande , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/patologia , Medula Óssea/patologia , Transdução de Sinais , Artrite Reumatoide/complicaçõesRESUMO
Patients with large granular lymphocytic leukemia (LGLL) frequently present with neutropenia. When present, anemia is usually accompanied by neutropenia and/or thrombocytopenia and isolated anemia is uncommon. We evaluated a cohort of 244 LGLL patients spanning 15 years and herein report the clinicopathologic features of 34 (14%) with isolated anemia. The patients with isolated anemia showed a significantly male predominance (p = 0.001), a lower level of hemoglobulin (p < 0.0001) and higher MCV (p = 0.017) and were less likely to have rheumatoid arthritis (p = 0.023) compared to the remaining 210 patients. Of the 34 LGLL patients with isolated anemia, 13 (38%) presented with pure red cell aplasia (PRCA), markedly decreased reticulocyte count and erythroid precursors, and more transfusion-dependence when compared to non-PRCA patients. There was no other significant clinicopathologic difference between PRCA and non-PRCA patients. 32 patients were followed for a median duration of 51 months (6-199). 24 patients were treated (11/11 PRCA and 13/21 non-PRCA patients, p < 0.02). The overall response rate to first-line therapy was 83% [8/11 (72.7%) for PRCA, 12/13 (92.3%) for non-PRCA], including 14 showing complete response and 6 showing partial response with a median response duration of 48 months (12-129). Half of non-PRCA patients who were observed experienced progressive anemia. During follow-up, no patients developed neutropenia; however, 5/27 (18.5%) patients developed thrombocytopenia. No significant difference in overall survival was noted between PRCA and non-PRCA patients. In summary, this study demonstrates the unique features of LGLL with isolated anemia and underscores the importance of recognizing LGLL as a potential cause of isolated anemia, which may benefit from disease-specific treatment. LGLL patients with PRCA were more likely to require treatment but demonstrated similar clinicopathologic features, therapeutic responses, and overall survival compared to isolated anemia without PRCA, suggesting PRCA and non-PRCA of T-LGLL belong to a common disease spectrum.
Assuntos
Anemia , Artrite Reumatoide , Leucemia Linfocítica Granular Grande , Aplasia Pura de Série Vermelha , Anemia/etiologia , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/patologia , Masculino , Aplasia Pura de Série Vermelha/complicaçõesAssuntos
Leucemia Linfocítica Granular Grande/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Leucemia Linfocítica Granular Grande/patologia , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/patologia , MasculinoRESUMO
RATIONALE: Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic clonal plasma cell or lymphoplasmacytic proliferative disorder. Recently, some case reports have described the association of pure red cell aplasia (PRCA) with MGUS, even with a relatively low monoclonal immunoglobulin burden. T large granular lymphocyte leukemia (T-LGLL) is a chronic lymphoproliferative disorder characterized by clonal expansion of T large granular lymphocytes, which is rare in China. There are some reports about T-LGL leukemia in patients with B-cell lymphoma; however, it is very rare that T-LGLL coexists with MGUS and clonal B-cell lymphoproliferative disorders (CB-LPD). PATIENT CONCERNS: A 77-year-old man was hospitalized because of anemia. He was diagnosed with MGUS, CB-LPD, and PRCA. During the development of the disease, a group of abnormal T lymphocytes was detected by flow cytometry of peripheral blood. DIAGNOSIS: Combining clinical manifestations with the result of T cell receptor gene rearrangement and immunophenotype, it was consistent with the diagnosis of T large granular lymphocyte leukemia. INTERVENTIONS: The patient was treat with bortezomib and dexamethasone regimen, Rituximab and sirolimus. OUTCOMES: The patient was transfusion independent after therapies. LESSONS: We report a patient with 4 concomitant hematological disorders: T-LGLL, MGUS, CB-LPD, and PRCA, aiming to represent the clinical and flow cytometry characteristics of these concomitant diseases, analyze the mechanism between diseases, and provide a clinical reference.
Assuntos
Leucemia Linfocítica Granular Grande/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Aplasia Pura de Série Vermelha/diagnóstico , Idoso , Anemia/etiologia , Antineoplásicos/uso terapêutico , Cloridrato de Bendamustina , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Aplasia Pura de Série Vermelha/complicações , Aplasia Pura de Série Vermelha/tratamento farmacológico , Rituximab/uso terapêutico , Sirolimo/uso terapêuticoRESUMO
Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T-LGL or NK cells. Chronic isolated neutropenia represents the clinical hallmark of the disease, being present in up to 80% of cases. New advances were made in the biological characterization of neutropenia in these patients, in particular STAT3 mutations and a discrete immunophenotype are now recognized as relevant features. Nevertheless, the etiology of LGLL-related neutropenia is not completely elucidated and several mechanisms, including humoral abnormalities, bone marrow infiltration/substitution and cell-mediated cytotoxicity might cooperate to its pathogenesis. As a consequence of the multifactorial nature of LGLL-related neutropenia, a targeted therapeutic approach for neutropenic patients has not been developed yet; moreover, specific guidelines based on prospective trials are still lacking, thus making the treatment of this disorder a complex and challenging task. Immunosuppressive therapy represents the current, although poorly effective, therapeutic strategy. The recent identification of a STAT3-mediated miR-146b down-regulation in neutropenic T-LGLL patients emphasized the pathogenetic role of STAT3 activation in neutropenia development. Accordingly, JAK/STAT3 axis inhibition and miR-146b restoration might represent tempting strategies and should be prospectively evaluated for the treatment of neutropenic LGLL patients.
Assuntos
Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/terapia , Neutropenia/complicações , Neutropenia/terapia , Diagnóstico Diferencial , Proteína Ligante Fas/metabolismo , Humanos , Imunofenotipagem , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/imunologia , Neutropenia/diagnóstico , Neutropenia/imunologia , PrognósticoRESUMO
Patients with primary immunodeficiency are at increased risk for malignancy, especially hematologic neoplasms. This paper reports a unique case of a 47-year-old man with X-linked agammaglobulinemia who presented with progressive asymptomatic violaceous papules and plaques on his face, hands, and trunk for 1 year. Skin biopsies revealed deep, nodular infiltrates of histiocytes and CD8-positive lymphocytes, with a CD4:CD8 ratio of 1:10. Laboratory studies showed cytopenias. Flow cytometry in the skin, blood, and bone marrow (BM) showed a CD3+/CD8+/CD57+ large granular lymphocyte population. BM biopsy showed 30% involvement with these atypical T-cells. T-cell gene rearrangement studies of skin, blood, and BM revealed identical T-cell clones. He was diagnosed with T-large granular lymphocyte leukemia (T-LGLL) with an associated CD8+ cutaneous lymphoproliferation. Skin involvement was suspected to represent infiltration by T-LGLL. However, co-existence of two lymphoproliferative disorders (LPDs), T-LGLL and CD8+ granulomatous LPD, remains a possibility. In general, cutaneous infiltrates associated with LGLL are rare and poorly understood. It has been suggested that they are markers of poor prognosis. Our case report describes skin, blood, and BM findings in an immunosuppressed patient with T-LGLL in detail. These findings have not yet been reported and their significance requires further investigation.
Assuntos
Agamaglobulinemia/genética , Linfócitos T CD8-Positivos/patologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/patologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/patologia , Biópsia , Medula Óssea/patologia , Linfócitos T CD8-Positivos/imunologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Rearranjo Gênico do Linfócito T , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Histiócitos/patologia , Humanos , Imiquimode/administração & dosagem , Imiquimode/uso terapêutico , Terapia de Imunossupressão/efeitos adversos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Pele/patologia , Resultado do TratamentoRESUMO
Severe thrombocytopenia (platelet count <50â000/µl) in pregnancy is uncommon and is generally considered a contraindication to neuraxial anesthesia. We present a case of a parturient who presented with severe thrombocytopenia secondary to bone marrow failure. After receiving platelet and cryoprecipitate transfusions to correct coagulopathy as verified by thromboelastometry, neuraxial anesthesia was safely utilized.
Assuntos
Anestesia Obstétrica/métodos , Leucemia Linfocítica Granular Grande/complicações , Testes de Função Plaquetária/métodos , Complicações Hematológicas na Gravidez/sangue , Tromboelastografia/métodos , Trombocitopenia/sangue , Adulto , Feminino , Humanos , Gravidez , Trombocitopenia/diagnósticoRESUMO
T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown.Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 109/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated.Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 109/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5-/dim on CD3+CD8+ T-lymphocytes was observed in both RA-associated T-LGLL and FS.STAT3 gene mutations or LGL counts over 2 × 109/L in RA patients are indicative of T-LGLL.
Assuntos
Artrite Reumatoide/complicações , Leucemia Linfocítica Granular Grande/genética , Adulto , Biomarcadores Tumorais/genética , Células da Medula Óssea/patologia , Diagnóstico Diferencial , Síndrome de Felty/diagnóstico , Síndrome de Felty/genética , Feminino , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Neutropenia , Estudos Retrospectivos , Fator de Transcrição STAT3 , Fator de Transcrição STAT5Assuntos
Cateterismo Cardíaco/métodos , Hipertensão Pulmonar , Células Matadoras Naturais/patologia , Leucemia Linfocítica Granular Grande , Idoso de 80 Anos ou mais , Antígenos de Superfície/análise , Contagem de Células Sanguíneas/métodos , Correlação de Dados , Diagnóstico Diferencial , Dispneia/diagnóstico , Dispneia/etiologia , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/imunologia , Leucemia Linfocítica Granular Grande/sangue , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/fisiopatologia , Leucemia Linfocítica Granular Grande/terapia , Masculino , Pessoa de Meia-Idade , Avaliação de Sintomas/métodosRESUMO
Large granular lymphocyte leukemia (LGL) is a clonal, lymphoproliferative disorder with an indolent disease course. T-cell LGL (T-LGL) is the most common type of LGL driven from T-cell lineage (85%). The coexistence of T-LGL with several types of autoimmune disorders, mostly rheumatoid arthritis (RA), has been reported. Felty's syndrome (FS) is defined by splenomegaly, low neutrophil count, and destructive arthritis and is usually seen in <1% of patients with RA. About 30% to 40% of patients with FS have been reported to have an expansion of large granulated lymphocytes in the circulation. FS and T-LGL are similar in terms of clinical manifestations, response to immunosuppressive therapy, their smoldering course, and immunogenetic findings, proposing FS and T-LGL with RA might be different aspects of a single disease spectrum. In this article, we present a case with long-standing RA who had never been on DMARD (Disease Modifying Anti-Rheumatic Drugs) treatment found to have constitutional symptoms, neutropenia, and splenomegaly, and the patient was diagnosed with T-LGL.
Assuntos
Artrite Reumatoide/complicações , Síndrome de Felty/complicações , Leucemia Linfocítica Granular Grande/diagnóstico , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Esplenomegalia/complicações , Linfócitos T/imunologiaRESUMO
OBJECTIVE: To explore the clinical effects of oral small dose of cyclophosphamide (CTX) in the treatment of T-cell large granular lymphocytic leukemia (T-LGLL) accompanied with pure red cell aplasia (PRCA). METHODS: The clinical features, characteristics of laboratory examinations and the process of oral small dose of CTX treatment after the ineffective treatment of cyclosporine A combining with prednisone in 1 case of T-LGLL with PRCA were reported and discussed with related references. RESULTS: The elderly female patient had indolent process, mainly presenting with anemia and significant low hyperplasia of bone marrow erythrocyte cells. Peripheral blood smear showed mainly with characteristic large granular lymphocytic morphology. The results of immunophenotypic analyses and genetic reassortment were compatible with T-LGLL. No effects were shown after 5 months of cyclosporine A combining with prednisone treatment and the patient still needed recurrent blood transfusion. CTX was prescribed as a second-line medication and the dose was 100 mg/d. Hemoglobin could returned to normal level and the efficacy remained for 1 year even after the medication was stopped. CONCLUSION: T-LGLL accompanied with PRCA is a rare disease and oral small dose CTX can be an effective therapeutic regimen.
Assuntos
Anemia Aplástica , Leucemia Linfocítica Granular Grande , Idoso , Anemia Aplástica/complicações , Ciclofosfamida , Eritrócitos , Feminino , Humanos , Leucemia Linfocítica Granular Grande/complicaçõesRESUMO
AIM: Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder associated with failure of hematopoiesis and autoimmune diseases. This study describes the clinical features and treatment responses of 108 patients with T-cell large granular lymphocyte leukemia (T-LGLL). METHODS: Clinical data were collected from T-LGLL patients treated at an anemia treatment center within the hematology and blood diseases unit of a single hospital from January 2009 to April 2019. RESULTS: The majority of patients (78 %) were symptomatic at the time of presentation. Splenomegaly was observed in 41 % of cases, while hepatomegaly and lymphadenopathy were rare (6 % and 7 %, respectively). Cyclosporine (CsA) monotherapy was used as first-line therapy for 16 patients, with an overall response rate (ORR) of 56 %. CsA in combination with steroids was administered in 83 patients, with an ORR of 48 %. Among patients experiencing relapse or resistance to first-line therapy, 10 received antithymocyte globulin (ATG) therapy, with an ORR of 50 %; an additional 9 patients received a modified regimen of high-dose cyclophosphamide (CTX) therapy, yielding an ORR of 78 %. CONCLUSIONS: This study provides new information regarding the clinical features and therapeutic strategies for T-LGLL, which can be used to improve clinical decision making for T-LGLL patients. The data presented here indicate the CsA is an effective option for the treatment of T-LGLL, while modified regimens of high-dose CTX or ATG are safe and effective choices for patients with CsA refractory disease.
Assuntos
Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Gerenciamento Clínico , Feminino , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Avaliação de Sintomas , Resultado do Tratamento , Adulto JovemRESUMO
Herein we report a case of sporadic inclusion-body myositis (sIBM) occurring at an unusually young age in a patient with primary Sjögren syndrome, and use the case to explore possible shared mechanisms for disease susceptibility. Possible factors may include the association of both conditions with the 8.1 ancestral haplotype; the presence of anti-cN1A antibodies, which, although considered specific for sIBM, are also seen in pSS; and the shared association with T-cell large granular lymphocyte leukemia (T-LGLL). Further evaluation of this patient did in fact reveal underlying T-LGLL and mechanisms by which T cells in sIBM may escape immune regulation and contribute to disease phenotype are explored. Despite myofiber infiltration with CD8-positive T cells in sIBM, and, although sIBM is traditionally considered treatment-refractory, we report a significant response to the anti-CD20 monoclonal antibody, rituximab, and discuss possible mechanisms by which this response may be mediated.
Assuntos
5'-Nucleotidase/imunologia , Autoanticorpos/imunologia , Leucemia Linfocítica Granular Grande/imunologia , Miosite de Corpos de Inclusão/imunologia , Síndrome de Sjogren/imunologia , Adulto , Azatioprina/uso terapêutico , Linfócitos T CD8-Positivos/patologia , Feminino , Antígenos HLA/genética , Haplótipos , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Leucemia Linfocítica Granular Grande/complicações , Imageamento por Ressonância Magnética , Metotrexato/uso terapêutico , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/complicações , Miosite de Corpos de Inclusão/patologia , Miosite de Corpos de Inclusão/terapia , Prednisolona/uso terapêutico , Rituximab/uso terapêutico , Síndrome de Sjogren/complicações , Síndrome de Sjogren/terapiaRESUMO
AIMS: The causes and diagnosis of 'double-negative' (CD3+CD4-CD8-) T-cell lymphocytosis are not well studied. We aimed to define the causes of double-negative T-cell lymphocytosis in children and adults, and to identify simple clinical and laboratory features that would help to differentiate between the underlying conditions. METHODS: We collected clinical and laboratory data on 10 children and 30 adults with significantly increased peripheral-blood double-negative T-cells (>10% of total lymphocytes). We identified conditions associated with double-negative T-lymphocytosis with flow cytometry, peripheral-blood morphology and T-cell receptor-gene rearrangement studies. Patients were assigned to diagnostic categories on the basis of these test results. RESULTS AND CONCLUSIONS: The causes of double-negative T-cell lymphocytosis in children were autoimmune lymphoproliferative syndrome (ALPS) and reactive γ/δ Τ-lymphocytosis. T-cell large granular lymphocyte (T-LGL) leukaemia, reactive γ/δ T-lymphocytosis and hepatosplenic T-cell lymphoma (HSTL) were the the most common disorders underlying double-negative T-cell lymphocytosis in adults. Less common causes included hypereosinophilic syndrome, peripheral T-cell lymphoma, ALPS and monoclonal, double-negative T-lymphocytosis of uncertain significance. CD5/CD7/Vδ2 expression and absolute double-negative lymphocyte count (<1.8×109/L) were useful discriminators for distinguishing patients with reactive γ/δ T-lymphocytosis from those with γ/δ lymphoproliferative disorders. Differentiating between γ/δ T-LGL and HSTL can be difficult. Expression of CD57 and cellular morphology (pale cytoplasm with distinct granules) would support a diagnosis of γ/δ T-LGL.