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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The syndrome of CD8 hyperlymphocytosis with neutropenia is a heterogeneous disorder ranging from reactive benign state to neoplastic pathology. The prognosis for LGL (Large Granular Lymphocyte) leukemia depends likely on its phenotype:-NK phenotype, extremely poor prognosis and rapidly fatal-T phenotype (CD8+), chronic disease with slow progression. Here, we report four cases of CD8+ hyperlymphocytosis with neutropenia, which are CD2+/-, CD3+, CD4-, CD8+, CD16-, CD56+/-, CD57+ phenotype. These lymphocytic proliferations were associated with clonal rearrangement of T-cell receptor b gene. In two cases, characteristic blood hyperlymphocytosis appeared only after splenectomy, but retrospective bone marrow analysis showed that the CD8+, CD57+ lymphocyte proliferation previously existed. These lymphocytes had a low natural killer activity against K562 cell line. HTLV1 proviral sequence was not integrated in leukemic cell DNA. This monoclonal pathology has a chronic clinical course, with a thirteen year evolution in one case. Splenectomy did not correct neutropenia but allowed the control of hemolytic anemia and auto-immune thrombocytopenia in one case.
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PMID:[Lymphoproliferative syndrome with granular lymphocytes of CD8+ phenotype: a clonal pathology with a chronic course]. 128 65

We report the findings in 21 Belgian patients (12 males and 9 females, median age 61 years) with LGLPD. Symptoms at presentation included infection (n = 9), weight loss (n = 5), asthenia (n = 9), pruritus (n = 2) and arthralgia (n = 7). Four patients were asymptomatic. The main clinical findings were hepatomegaly (n = 5), splenomegaly (n = 8), lymph node enlargement (n = 3) and arthritis (n = 5). All patients had an increased LGL count associated with anemia (n = 12), neutropenia (n = 17), often less than 0.5.10(9)/L (n = 10) and thrombocytopenia (n = 6). Three patterns of lymphocyte surface markers were observed: CD3+CD4-8+ (14 patients), CD3+CD4-8+ (5 patients) and CD3+CD4+8- (1 patient). An abnormal karyotype was found in 2 patients. T-cell receptor gene was rearranged in all cases tested (9/9).
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PMID:Large granular lymphocyte proliferative disease: 21 Belgian cases and review of the literature. 131 80

LGL leukemia results from a chronic, clonal proliferation of LGL. Chronic neutropenia with recurrent bacterial infection and splenomegaly are common clinical manifestations. Rheumatoid arthritis coexists in some of these patients, who thus resemble patients with Felty syndrome. Other hematologic abnormalities that may occur include pure red-cell aplasia and adult-onset cyclic neutropenia. Lymphoid infiltration of bone marrow, splenic red pulp cords, and hepatic sinusoids is characteristic; lymph node and skin involvement are rare. Multiple serologic abnormalities are frequently present, including positive tests for rheumatoid factor and/or antinuclear antibody, polyclonal hypergammaglobulinemia, and circulating immune complexes. Antineutrophil and antiplatelet antibodies are often present. Leukemic LGL exhibit phenotypic heterogeneity; the most common phenotype in our patients is CD2+, CD3+, CD8+, HNK-1+, CD16-. Despite markedly increased numbers of LGL, functional activity of the cells is usually decreased. The mechanism of cytopenias is uncertain: in pure red-cell aplasia, it appears to be due to suppressive effect on erythropoiesis by abnormal LGL, but in patients with chronic neutropenia it may be antibody-mediated. Although most patients appear to have a relatively benign clinical course, mortality from infections and progressive lymphoproliferation is substantial. Optimal therapy remains undefined. Some preliminary evidence suggests that LGL leukemia may be associated with infection with a retrovirus similar to HTLV-I. Although relatively rare, LGL leukemia is of interest because a better understanding of this disease process may contribute to our knowledge of autoimmune diseases, the immunoregulatory functions of LGL, and the mechanisms controlling normal hematopoiesis.
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PMID:Large granular lymphocyte leukemia. Report of 38 cases and review of the literature. 362 48

Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) beta chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR V beta chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared V beta usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation.
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PMID:Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor V beta-specific monoclonal antibodies. 762 87

Morbidity and mortality in patients with T large granular lymphocyte (T-LGL) leukemia result from infections acquired during severe neutropenia. Optimum treatment for severe neutropenia remains undefined. We conducted an uncontrolled but prospective study of low-dose oral methotrexate, up to 10 mg/m2 weekly, in 10 patients with this disease. Therapeutic response was assessed by serial clinical evaluations and laboratory determinations including complete blood counts, lymphocyte phenotyping, and T-cell receptor gene rearrangement studies. A partial response was defined as a sustained increase in neutrophil count greater than 500/microL. A complete clinical remission was defined as achievement of a normal complete blood count and CD3+ LGL count. Previous prednisone treatment in eight of these patients had produced one clinical remission and four partial responses; tapering of prednisone in each of these patients resulted in recurrence of severe neutropenia. Five patients in this study received both methotrexate and tapering doses of prednisone. Complete clinical remissions on methotrexate were observed in five patients; an additional patient had a partial response. Molecular analyses of T-cell receptor gene rearrangement could not detect the abnormal clone in three of five patients achieving a complete clinical remission. Two weeks to 4 months of therapy were needed before attaining a neutrophil count greater than 500/microL. Complete and partial responses have been maintained on therapy, with a follow-up period ranging from 1.3 to 9.6 years. Low-dose oral methotrexate therapy is an effective treatment for some patients with LGL leukemia.
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PMID:Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. 791 31

Three distinct clinical syndromes occur in patients with increased numbers of circulating LGL. Patients with T-LGL leukemia have clonal proliferations of CD3+ LGL typically associated with chronic neutropenia and autoimmune features. NK-LGL leukemia is characterized by clonal CD3- LGL proliferation with an acute clinical presentation marked by massive hepatosplenomegaly and systemic illness. However, most patients with increased numbers of CD3- LGL do not have clinical features of NK-LGL leukemia and have a chronic clinical course. X-linked gene analyses have supported a polyclonal LGL lymphocytosis in this syndrome. Further studies are needed to determine whether clonal progression can occur in these patients.
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PMID:Clonal diseases of large granular lymphocytes. 827 46

The association of large granular lymphocyte leukemia (LGL-L) with hepatocellular carcinoma in a 55-year-old patient is described. An increased number of LGL was seen on peripheral blood smears. The immunophenotype was CD3+, CD4-, CD8+, and a study of the TCR gene rearrangement indicated the monoclonal nature of the proliferation. A liver mass was detected on CT scan and an ultrasound-guided fine needle biopsy revealed the presence of hepatocholangiocellular elements. A right hepatectomy was performed. Major neutropenia persisted despite corticosteroids and granulocyte colony-stimulating growth factor (G-CSF) therapy. Methotrexate at 20 mg/week failed to control lymphocytosis after three months of treatment. A new nodule of hepatocarcinoma reappeared twelve months after surgery and a liver resection was performed.
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PMID:Large granular lymphocyte leukemia associated with hepatocellular carcinoma: a case report. 864 51

The prevalence of humoral immune dysfunction has not been defined in a large series of patients with T-cell large granular lymphocyte leukemia (T-LGL) confirmed to be clonal by T-cell receptor analysis. Therefore we evaluated the presence of multiple autoantibodies in 27 patients with this disease. Humoral immune abnormalities included: rheumatoid factor (RF) (15/27 patients), antinuclear antibody (ANA) (13/27 patients), polyclonal hypergammaglobulinemia (15/24 patients), elevated serum immunoglobulins (17/26 patients), immune complex formation (18/25 patients), elevated beta-2 microglobulin (13/18 patients) and neutrophil-reactive IgG (18/20 patients). Disease manifestations in these patients were due to complications of cytopenia or autoimmune abnormalities. Infection was a common finding (21/27 patients) and likely reflected their neutropenia. Rheumatoid arthritis (11/27 patients), anemia (12/27 patients) and thrombocytopenia (10/27 patients) were less common but still frequently observed. This study demonstrates the presence of multiple autoantibodies in a large series of patients with documented clonal T-LGL proliferations.
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PMID:Humoral immune abnormalities in T-cell large granular lymphocyte leukemia. 903 Nov 18

A 24 year old female with a 4 year history of anemia and absolute lymphocytosis was evaluated and found to have T cell large granular lymphocyte (T-LGL) leukemia associated with autoimmune hemolytic anemia, neutropenia, mild thrombocytopenia and splenomegaly. In an effort to ameliorate her symptomatic cytopenias, she was treated with prednisone and subsequently methotrexate without success. In February 1993, she underwent splenectomy for symptomatic anemia. Splenectomy resulted in an increased hemoglobin concentration to normal levels, resolution of all laboratory evidence of hemolysis, and disappearance of thrombocytopenia. This response has been durable despite persistence of the abnormal LGL clone. We suggest that splenectomy may be an effective treatment for autoimmune hemolytic anemia and/or thrombocytopenia often associated with T-LGL leukemia. As this disease often exhibits a chronic clinical course with morbidity resulting from consequences of resultant cytopenias rather than visceral involvement with leukemic LGL, effective treatment of cytopenias despite persistence of the abnormal LGL clone is beneficial.
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PMID:Resolution of autoimmune hemolytic anemia following splenectomy in CD3+ large granular lymphocyte leukemia. 903 Nov 24

T cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) and large granular lymphocyte leukemia of T or NK cell type (T-LGL or NK-LGL leukemia) are chronic lymphoproliferative diseases derived from post-thymic immunocompetent lymphoid cells. T-PLL is morphologically characterized by a prominent central nucleolus in a medium-sized cell expressing a mature T cell immunophenotype. Clonal genetic changes involving chromosome 14 and T cell receptor gene rearrangements are characteristics of these diseases. They are usually progressive and there is no efficient treatment available. The classification of some cases presenting with a morphological picture similar to B-CLL, but with immunophenotypic and clinical features resembling T-PLL, as T-CLL is still controversial. The phenotypic profiles and the establishment of clonality are the hallmarks of defining T-LGL leukemia and NK-LGL leukemia. The CD3+/CD57+/CD56- immunophenotype and the clonal rearrangement of the T cell receptor genes characterize T-LGL leukemia, which presents clinically with a rather indolent course of disease, complicated by frequent infections secondary to neutropenia. NK-LGL leukemia cells express CD3-/CD56+/CD57-, but in most cases clonality cannot easily be established. Clinically the patient may either present with constitutional symptoms and suffer a short and aggressive course of disease or may have a more chronic disease similar to T-LGL leukemia. Therefore, it may be reasonable to subdivide NK-LGL proliferation into the more aggressive 'NK-LGL leukemia/lymphoma' and 'chronic NK cell lymphocytosis'.
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PMID:Chronic lymphatic leukemias of T and NK cell type. 917 39


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