Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 54-year-old woman presented with a severe autoimmune anemia, thrombocytopenia, neutropenia (Evans' syndrome), and CD8+ lymphocytosis, without signs of lymphadenopathy or splenomegaly. A diagnosis of T cell large granular lymphocyte (T-LGL) leukemia was made, based on cytomorphology, the typical CD3+/CD4-/CD8+/CD16+/CD56-/CD57-/HLA-DR(+/-) immunophenotype of the lymphocytosis (9 x 10(9)/l), and biallelic clonally rearranged T cell receptor beta (TCR beta) genes. Clonality of the TCR alphabeta+ T-LGL was also demonstrated with a panel of antibodies against variable domains of TCR beta chains, which showed single Vbeta7.1 expression on the CD3+ T-lymphocytes. After treatment failure with corticosteroids, splenectomy, and cyclophosphamide, respectively, a complete clinical remission was induced and sustained with cyclosporin A. Vbeta7.1/CD8/CD3 triple immunofluorescence stainings appeared to be valuable for titrating the cyclosporin A dosage by monitoring the T-LGL cells during treatment.
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PMID:Induction of clinical remission in T-large granular lymphocyte leukemia with cyclosporin A, monitored by use of immunophenotyping with Vbeta antibodies. 951 76

T-cell large granular lymphocyte (T-LGL) leukemia is clinically indolent, but is associated with severe neutropenia in approximately 50% of cases. The pathogenesis of the neutropenia is unclear. We report reversal of severe neutropenia associated with T-LGL leukemia in five patients treated with cyclosporine (CSA). All five had persistent neutrophil counts below 0.5 x 10(9)/L, two had agranulocytosis, and four had recurrent infections. Increased populations of LGL were present in blood and marrow, with a T-LGL immunophenotype (CD3(+)CD8(+)CD16(+/-)CD56(+/-)CD57(+)) shown by multiparameter flow cytometry, and clonal T-cell receptor (TCR) gene rearrangements in two of two pretreatment blood samples studied. CSA was initiated at doses of 1 to 1.5 mg/kg orally every 12 hours, with subsequent dose adjustments based on trough serum levels. Four patients attained normal neutrophil counts with CSA alone; one required addition of low-dose granulocyte-macrophage colony-stimulating factor. Time to attainment of 1.5 x 10(9)/L neutrophils ranged from 21 to 75 days. Attempts to taper and withdraw CSA resulted in recurrent neutropenia. Three patients have maintained normal neutrophil counts on continued CSA therapy for 2, 8, and 8.5 years. Two patients died 1.7 and 4.6 years after initiation of CSA despite normal neutrophil counts-one of metastatic melanoma and one of complications after aortofemoral bypass surgery. Despite resolution of neutropenia, increased populations of T-LGL cells have persisted in all patients during CSA therapy, as shown by morphology and flow cytometry and by the presence of clonal TCR gene rearrangements in four patients' posttreatment blood samples. We conclude that CSA is an effective therapy for neutropenia associated with T-LGL leukemia, and that resolution of neutropenia despite persistence of abnormal cells implies that CSA may inhibit T-LGL secretion of yet unidentified mediators of neutropenia.
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PMID:Neutropenia associated with T-cell large granular lymphocyte leukemia: long-term response to cyclosporine therapy despite persistence of abnormal cells. 955 95

Natural killer cell activity (Nka) of peripheral blood mononuclear cells (PBMCs) against K562 cell targets was assessed in 66 patients with chronic idiopathic neutropenia of adults (CINA) using the 16-h 51Cr-release assay. It was found that CINA patients exhibited significantly lower Nkr than normal subjects, which strongly correlated with the degree of neutropenia and the numbers of circulating neutrophils. Patients' NKa was increased by recombinant human interleukin-2 (rhIL-2) or recombinant human interferon-alpha (rhIFN-alpha), but the values obtained did not reach the respective NKa values found in normals. However, percentages of cytokine-induced rises of NKa did not differ statistically between patients and normal subjects. No serum inhibitors of NKa were demonstrated in our patients. CINA patients had low numbers of circulating NK cells as defined by the expression of NK-cell-related surface markers CD16, CD56, and CD57. CD16+ and CD56+, but not CD57+, cells correlated with the values of baseline NKa. The numbers of all these cell subsets correlated with the degree of neutropenia and the numbers of circulating neutrophils. Using CD56+-enriched PBL suspensions, it was shown that patients' NK cells displayed normal tumor cell binding capacity and produced in vitro normal amounts of natural killer cytotoxic factor(s) against K562 cell targets upon activation with rhIFN-alpha. Finally, percentages of perforin-expressing and granzyme B-expressing CD16+ cells did not differ statistically between patients and normal controls. Based on all these observations, we concluded that CINA patients display low NKa probably because they have low numbers of circulating NK cells. No functional abnormalities of NK cells were demonstrated. The cause and the underlying mechanisms leading to NK-cell depletion in these patients remain to be clarified.
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PMID:Defective natural killer cell activity of peripheral blood lymphocytes correlates with the degree of neutropenia in patients with chronic idiopathic neutropenia of adults. 961 29

We report a case of granular lymphocyte proliferative disorder accompanied with hemolytic anemia and neutropenia. Phenotypes of the cells were T cell receptor gammadelta+ CD3+ CD4- CD8+ CD16+ CD56- CD57-. Southern blot analysis of T cell receptor beta and gamma chains demonstrated rearranged bands in both. Chromosomal analysis after IL-2 stimulation showed deletion of chromosome 6. Sorted gammadelta+ T cells showed an increase in Fas ligand expression compared with the levels in sorted alphabeta+ T cells. The expression of Fas ligand on these gammadelta+ T cells increased after IL-2 stimulation. The patient's anemia improved along with a decrease in granular lymphocyte count and disappearance of the abnormal karyotype without treatment. The expression of Fas ligand may be involved in spontaneous regression of granular lymphocyte proliferation with hemolytic anemia.
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PMID:Abnormal proliferation of CD4- CD8+ gammadelta+ T cells with chromosome 6 anomaly: role of Fas ligand expression in spontaneous regression of the cells. 1020 5

Chronic natural killer (NK) lymphocytosis involves a persistent increase in CD56+ large granular lymphocytes (LGLs) that is sometimes associated with immune-mediated complications, such as anemia and neutropenia. However, aplastic anemia (AA) is a rare complication. Here we describe 2 patients with severe AA who presented with persistent increases in NK cells. Their LGLs were positive for CD56, CD16, and intracellular interferon (IFN)-gamma but negative for CD3, Fas-ligand, and T-cell receptor rearrangement, findings that are compatible with NK cells. Not only the number of NK cells, but NK activity as well, was increased in both patients. The number of NK cells changed according to hematologic recovery and relapse in 1 case. Thus, there seemed to be a close relationship between NK cells and the progression of AA, at least in this instance. Further investigation of the clinical course of similar cases and the characteristics of NK cells is necessary.
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PMID:Severe aplastic anemia associated with chronic natural killer cell lymphocytosis. 1119 12

It has been suggested that some cases of nonimmune chronic idiopathic neutropenia of adults (NI-CINA) may be considered preleukemic disorders. This paper describes two patients with NI-CINA who developed acute myeloid leukemia (AML) 34 and 64 months, respectively, following NI-CINA diagnosis. Patient 1 presented erythema nodosum and patient 2 polyarthritis of the large joints 9 and 2 months, respectively, before AML. Patient 1 had AML M4 disease associated with aberrant expression of CD7 and CD19 cell surface markers and one abnormal clone in bone marrow karyotype. Patient 2 had myeloid/natural killer (NK) cell leukemia with expression of CD7 and CD56 molecules and four derivative abnormal clones in the karyotype. Both patients had del(5)(q22q35) in common. No mutations in the transmembrane or the intracytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor were found. The first patient had disease resistant to chemotherapy from the beginning of the treatment and the second following a brief complete hematological remission. On the basis of these observations, we concluded that a causal link of AML with the underlying NI-CINA cannot be presently justified, but the unusual findings noted in our patients prompt the description of additional cases for a further investigation of the relationships, if any, between these two granulocytic disorders.
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PMID:Two patients with nonimmune chronic idiopathic neutropenia of adults developing acute myeloid leukemia with aberrant phenotype and complex karyotype but no mutations in granulocyte colony-stimulating factor receptor. 1180 37

There have been few reports of large granular lymphocyte (LGL) leukemia with neutropenia complicated with pure red cell aplasia (PRCA) that developed after human parvovirus (HPV) B19 infection. We report here the case of a 35-year-old female who developed HPV B19-associated PRCA with T-LGL leukemia. LGL count of peripheral blood was lower than 2 x 10(9) l(-1), although phenotypic analysis of LGL showed CD3+, CD16-, CD56-, CD57+ with double positive for CD3 and CD57, and genetic study showed the clonal rearrangement of T-cell receptor gene. Microscopically, the patient's bone marrow showed characteristic giant proerythroblasts. A serologic study of HPV B19 was positive for IgM, but negative for IgG, with a positive result on Dot-blot hybridization assay for HPV B19 DNA. Severe anemia and reticulocytopenia ameliorated without treatment 10 days after the initial examination, but slight anemia, neutropenia, a moderate increase of LGL counts with rearrangement of TCR gene, and positive result of HPV B19 DNA has persisted 7 months after the initial examination. We suggest that this viral infection may play an etiologic role in some patients with LGL leukemia who develop PRCA.
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PMID:Pure red cell aplasia associated with parvovirus B19 infection in T-large granular lymphocyte leukemia. 1191 33

We report a case of CD8(+)/V beta 5.1(+) T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3(+)/TCR alpha beta(+)/CD8(+bright)/CD11c(+)/CD57(-)/CD56(-) large granular lymphocytes with expression of the TCR-V beta 5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR beta-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V beta monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease.
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PMID:Cd8(+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin. 1211 71

This article describes a rare case of bone marrow transplantation (BMT) from an unrelated donor (URD) in an adult Japanese male with Down syndrome (DS) diagnosed as having acute mixed lineage leukemia. Examination of peripheral blood demonstrated WBC 6.2 x 10(9)/l with 45.5% blasts at admission. Leukemic blasts with positive peroxidase stain, but negative periodic acid-Schiff stain comprised 91.6% on bone marrow specimen. Surface marker analysis of these blasts showed the following: CD3(-), CD5(-), CD7(-), CD10(+), CD19(+), CD13(+), CD14(-), CD33(+), CD34(+), CD41a(-), and CD56(-). Based on these data, he was diagnosed as having acute mixed lineage (myeloid and B-lymphoid lineage) leukemia. He achieved complete remission (CR) by lymphoid-oriented chemotherapy performed after ineffective myeloid-oriented therapy. After four courses of consolidation chemotherapy for lymphoid lineage blasts, recurrence due to proliferation of myeloblasts had occurred. Thereafter, a second CR was obtained by low dose cytosine arabinoside (AraC) therapy. As this patient was considered to have a high risk of relapse, we selected allogeneic BMT from URD. Severe stomatitis due to methotrexate (MTX) occurred probably due to altered pharmacokinetics usually observed in DS patients. Though acute graft-versus-host disease (GVHD) of systemic skin (grade II) and pneumonia were observed during neutropenia due to the post-conditioning regimen, he could be discharged from our hospital on the 135th day after BMT. On day 205 post-BMT, however, bronchiolitis obliterans (BO) occurred as a chronic GVHD disorder. Despite therapy with prednisolone and FK506, he died on day 400 post-BMT because of respiratory failure due to BO. In DS patients, superfluous toxicities due to MTX and AraC treatment have been reported, and these toxicities have been considered due to altered pharmacokinetics in patients with DS. This patient could tolerate the transplant conditioning regimen commonly used in patients without DS.
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PMID:Unrelated donor bone marrow transplantation for acute mixed lineage (myeloid and B-lymphoid lineage) leukemia in an adult with Down syndrome. 1270 27

We report a case of natural killer (NK) cell leukemia with unusual biological features in a 65-year-old woman with a 20-year history of rheumatoid arthritis. She presented with neutropenia, thrombocytopenia, splenomegaly and bone marrow infiltration. Immunophenotyping (CD2+ CD3- CD4- CD5- CD8- CD16+ CD56-) confirmed NK cell leukemia. Her neutropenia and thrombocytopenia resolved following splenectomy and she has remained well with stable disease for 12 months on oral low-dose methotrexate. In contrast to all previous reports, in this instance the phenotype of large granular lymphocytic (LGL) leukemia occurring in the context of rheumatoid arthritis was NK-cell rather than T-cell. Furthermore, the clinical course was indolent, whereas, all prior literature reports have described a very aggressive clinical course for this disorder with a median survival of just 3.5 months. This case illustrates previously unrecognized heterogeneity in the natural history of this disorder.
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PMID:A case of clinical indolent natural killer cell lineage large granular lymphocytic leukemia in a patient with rheumatoid arthritis. 1291 76


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