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

Large granular lymphocytosis (LGL) is characterized by enhanced proliferation of T lymphocytes that have antibody-dependent cell-mediated cytotoxicity or natural killer cell activity and that often produce severe cytopenias, including neutropenia. When a 68-year-old man with seropositive rheumatoid arthritis and severe neutropenia was examined, he was found to have LGL with a T cell gene rearrangement, indicating the presence of a clonal population of T lymphocytes. The patient was admitted with a fever of 102 degrees F and a nonhealing ulcer over the right tibia. When the infection did not respond to intravenous antibiotics, granulocyte colony-stimulating factor (GCSF) therapy was started at 5 micrograms/kg subcutaneously each day. The neutrophil count promptly increased and the patient subsequently defervesced and was able to have a skin graft placed, which healed without difficulty. GCSF, which is known to be an effective therapeutic agent for neutropenia associated with chemotherapy and bone marrow transplantation, also was a very valuable treatment for the life-threatening neutropenia of LGL.
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PMID:Case report: granulocyte colony-stimulating factor overcomes severe neutropenia of large granular lymphocytosis. 128 Sep 8

The toxicity and/or the stimulation of natural killer cell activity that resulted from exposure to alpha-interferon varied according to circadian dosing time, both in mice and in human beings. Ten patients with advanced renal cell carcinoma or melanoma were treated with recombinant alpha-interferon-2b using a continuous 21-day intravenous schedule at circadian modulated rate. Patients received 15-20 MU/m2/day in an ambulatory care program. The drug was delivered via an external programmable-in-time pump. Thirty-nine courses of therapy were given (2-12 courses per patient). Severe side effects included World Health Organization grade III somnolence (one patient, 1 course) and grade III-IV neutropenia (five patients, 10 courses). Karnofsky performance status decreased by 40% in 3 patients (five courses). Two of these patients were withdrawn from the study because of toxicity. Disease was stabilized in four of the seven patients evaluable for response. Seven of the 10 patients are alive at 15 months' median follow-up. Two have continued with chronotherapy for 9+ and 13+ months, respectively. A large interpatient variability characterized the maximally tolerated dose. Two patients led their usual activities while receiving 20 MU/m2/day for three courses or more. Conversely, two patients exhibited severe side effects with 10 MU/m2/day. As compared with schedules of standard administration or continuous flat infusion, this circadian schedule of infusion allowed a large increment in total daily dose and dose intensity. A starting dose of 15 MU/m2/day was well tolerated by 8 of 10 patients and can be recommended using this circadian modulated schedule.
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PMID:A phase I trial of 21-day continuous venous infusion of alpha-interferon at circadian rhythm modulated rate in cancer patients. 176 78

Several reports describe the association of hyperlymphocytosis with neutropenia. This syndrome, named lymphoproliferative disease, is characterized by a chronic indolent clinical course, bone marrow lymphocyte infiltration, and granulopenia of central origin. The proliferating lymphocytes share large granular lymphocyte natural killer cell and T-lymphocyte characteristics. They are either of monoclonal or polyclonal origin. In this report the familial occurrence of a similar syndrome observed in two children is described. Lymphocyte morphologic abnormalities including nuclear pockets, were noted, a feature usually present in leukemic cells. Lymphocyte proliferation was distinct in each case as shown by the presence of a predominant CD4+ cell population in one and a predominant CD8+ population in the other. Monoclonal gene rearrangements of T-cell receptor beta-chain gene were found although clonal variations occurred with time in one patient. The cause of this unique familial occurrence of monoclonal lymphoproliferation associated with neutropenia is unknown.
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PMID:A familial occurrence of natural killer cell--T-lymphocyte proliferation disease in two children. 184 90

The healthy mother of a child with transient immune neutropenia was found to be "NA-null." The mother's neutrophils did not react with anti-NA1 and anti-NA2 antibodies (polyclonal human alloantibodies and mouse monoclonal antibodies). A healthy donor was discovered during routine neutrophil antigen typing whose neutrophils were also "NA-null." This NA-phenotype was due to the absence of FcRIII (CD16 antigen) on neutrophils as demonstrated with anti-FcRIII monoclonal antibodies. The neutrophils of these two individuals were not able to bind dimeric immunoglobulin G. However, their cells had a normal expression of other phosphatidylinositol (PI)-linked membrane glycoprotein (CD24, CD67, and CLB gran/5 antigens), ruling out the existence of a PI-linkage defect, such as paroxysmal nocturnal hemoglobinuria. The mother (propsitus) had isoantibodies in her blood against neutrophil-FcRIII without allospecificity, apparently produced during pregnancy and responsible for the neutropenia of her child. The expression of FcRIII on natural killer lymphocytes of both individuals was normal. FcRIII is encoded by two separate genes, one (FcRIII-1) for the neutrophil-PI-linked receptor, another (FcRIII-2) for the natural killer cell and macrophage-transmembrane receptor. By messenger RNA and DNA analysis (with an FcRIII-cDNA probe and restriction endonucleases) the neutrophil-FcRIII deficiency appeared to be due to deletion of the FcRIII-1 gene in both individuals, while the FcRIII-2 gene was normally present. The parents of the propositus were found to be heterozygous for this defect. Thus, FcRIII-1 gene deficiency of the mother may be a cause of (iso)immune neutropenia of the newborn. Whether this deficiency may have other clinical consequences has to be studied.
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PMID:Maternal genomic neutrophil FcRIII deficiency leading to neonatal isoimmune neutropenia. 183 May 1

Fanconi anaemia (FA) is a recessively inherited disorder associated with a typical physical appearance and a spectrum of clinical and laboratory characteristics. Parental heterozygotes of FA patients are superficially normal in appearance and lack overt laboratory abnormalities. Furthermore, they are indistinguishable from normal subjects on chromosome analysis. In order to determine if any of the clinical or laboratory abnormalities seen in FA patients were detectable to a lesser degree in heterozygotes, we carried out detailed skeletal measurement and laboratory investigation on 16 obligate FA heterozygotes and compared the results with 40 normal control subjects. Skeletal proportions in FA heterozygotes showed significant differences from normal subjects in the ratio of the height to the inter-acromial distance (p less than 0.001), and in having significantly shorter forearms (p less than 0.05). Apart from two patients with presumed iron deficiency, haemoglobin levels were normal, but three patients showed neutropenia (less than 1.5 X 10(9)/l). Foetal haemoglobin measurements were significantly higher (p less than 0.01) and natural killer cell subsets lower (p less than 0.05) in heterozygotes. Significantly reduced mitogenetic responses to phytohaemagglutinin and interleukin-2 of peripheral blood lymphocytes in heterozygotes was also demonstrated. These results suggest that heterozygotes show minor physical and haematological abnormalities consistent with partial expression of the Fanconi gene in the heterozygote.
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PMID:Physical and laboratory characteristics of heterozygote carriers of the Fanconi aplasia gene. 226 25

This report describes alterations in functional responses to lectin-induced stimulation of peripheral blood lymphocytes and in the natural killer cell (NKC) activity, of college students, obtained during an outbreak of influenza A/Philippines/2/82(H3N2) virus infection. These results are compared with similar observations in college students with an acute, febrile, noninfluenzal respiratory illness that occurred during the same outbreak. The lymphopenia typical of influenza during acute illness was shown to be due to a reduction in both T and B cells without alteration in the CD4:CD8 ratio. In addition, phytohemagglutinin and concanavalin A responses were reduced and NKC activity was increased, while pokeweed mitogen reactivity was unaltered at the time of admission to the study. Patients with noninfluenzal illness showed early polymorphonuclear leukocytosis and a similar lymphopenia. Lymphocyte functions were virtually unchanged during acute illness in noninfluenza patients. The relatively specific alterations in lymphocyte responses to lectin-induced stimulation in influenza patients may indicate that the peripheral T cells are incapable of activation via the CD3 or CD2 activation pathways. In addition, increased NKC activity in the periphery may be reflective of increased NKC activity in the lung. Influenza-infected individuals with higher NKC activity at the time of admission to the study also took longer to recover. Finally, the early lymphopenia and the later neutropenia in the influenza-infected patient may represent migration of these cells from the circulation to the infected respiratory tract as a consequence of infection.
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PMID:Influenza virus infection induces functional alterations in peripheral blood lymphocytes. 243 Oct 43

Thirteen patients with metastatic malignant melanoma received interferon alpha-2a (Roferon-A) and vinblastine. The interferon dosage was increased from 3 x 10(6) IU to 9 x 10(6) IU daily in 10 weeks and thereafter 9 x 10(6) IU was administered three times weekly intramuscularly. Vinblastine (0.075-0.15 mg/kg) was given every third week intravenously. One of the ten evaluable patients had partial remission (PR) (11%) for 10 months. The diseases was stabilized (NC) in three patients (30%) for 3, 6 and 9 months. Progression (PD) occurred in six patients. The treatment time varied from 5 weeks to 44 weeks. The median survival time from the beginning of this combination treatment was 5 months. The most common side-effects were fever, fatigue, loss of taste, weight loss and neutropenia. The mitogen response to phytohemagglutinin and purified protein derivative of tuberculin decreased in all patients. The response to concanavalin A decreased less and began to increase again in the patients with PR and NC. The natural killer cell activity in PD patients decreased more than in the patients with PR and NC. The ratio of T4/T8-positive cells was restored in PR + NC patients but rose in PD patients indicating a difference in the immunomodulatory effect of the combination or of the advanced disease itself on T-cell function in PD patients. This combination of daily interferon and vinblastine did not prove to be effective in melanoma. The depression of immunological functions, which was more marked in patients with PD, might indicate that vinblastine in this combination counteracts the immunostimulatory effect of interferon.
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PMID:Combined interferon and vinblastine treatment of advanced melanoma: evaluation of the treatment results and the effects of the treatment on immunological functions. 278 56

A 74 year old woman with rheumatoid arthritis, hepatosplenomegaly, neutropenia, and peripheral blood lymphocytosis is described. The lymphocytes had a large granular morphology and expressed a CD3+ CD8+ Leu7+ surface antigen phenotype. They did not have natural killer cell function. Southern analysis of the lymphocyte DNA using two restriction enzymes showed a rearranged pattern for the T cell receptor beta chain gene, indicating a monoclonal lymphoproliferation. Large granular lymphocytosis is a rare and heterogeneous phenomenon, which has become more clearly characterised through the application of molecular biology techniques. Most cases appear to be forms of T cell leukaemia with a chronic benign course. The association between rheumatoid arthritis and large granular lymphocytosis is emphasised.
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PMID:Large granular lymphocytosis associated with rheumatoid arthritis. 284 61

An immunoperoxidase technique was used to examine the distribution of lymphocyte subsets in bone marrow biopsies of 15 patients with neutropenia and seven non-neutropenic controls. The bone marrow of most patients and controls had similar distributions of immune effector cells characterized by a diffuse array of predominantly cytotoxic/suppressor T-cells and occasional nodular aggregates of helper T-cells. Cells displaying the natural killer cell marker HNK-1 were sparse in controls and most neutropenic patients. However, marked increases in marrow HNK-1 + cells were identified in four of the 15 patients. Three of these patients had diffuse HNK-1 + infiltrates associated with increased Leu 4+ (OKT-3+) T-cells while one had a nodular HNK-1+ infiltrate associated with small B-cell follicles. Each of these patients had clinical features similar to those described in the large granular lymphocyte (LGL) lymphocytosis (leukemia) syndrome, but only one of four demonstrated persistently increased numbers of LGLs in the peripheral blood. Thus, this study extends the association of neutropenia and increased numbers of cells with a T/NK phenotype to include patients whose bone marrow is the only demonstrable site of involvement. Since morphologic examination of the bone marrow could not identify the bone marrows with increased HNK-1+ cells, immunologic techniques are required to detect these cases.
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PMID:Immunoarchitecture of the bone marrow in neutropenia: increased HNK-1 + cells define a subset of neutropenic patients. 357 62

We describe a patient with neutropenia associated with increased circulating large granular lymphocytes (LGL). Absolute neutropenia was accompanied by the absence of myeloid precursor cells in the bone marrow. No myeloid progenitor cells (CFU-C) could be detected by in vitro colony culture. The peripheral blood was also remarkable for the presence of a population of large granular lymphocytes demonstrable by conventional staining. These cells in flow microfluorometry studies expressed antigens Leu 4 (T-cell antigen receptor), Leu 7 (natural killer cell marker), Leu 2 (suppressor cell marker), and HLA-DR (activation marker); they lacked Leu 1 (a pan-T cell antigen), Leu 3 (helper cell marker) and Tac (interleukin 2 receptor). Hematopoietic colony formation in vitro improved with addition of corticosteroids to the culture medium or elimination of the LGL population with complement-mediated cytotoxicity. Anti-neutrophil antibodies were present prior to and following therapy. Clinically, administration of prednisone resulted in a normalization of the total white blood cell count and absolute polymorphonuclear cell number, an increase into the normal range of the number of CFU-C, and elimination of the LGL population. In this case of steroid-responsive LGL-associated neutropenia, laboratory studies suggested direct suppression of myelopoiesis by steroid-responsive LGL.
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PMID:Neutropenia associated with large granular lymphocytes responsive to corticosteroids in vitro and in vivo. 358 9


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