1/38. Clonal expansion of gammadelta-T lymphocytes in an HTLV-I carrier, associated with chronic neutropenia and rheumatoid arthritis.We report on an HTLV-I carrier showing clonal proliferation of gammadelta-T lymphocytes associated with chronic neutropenia and rheumatoid arthritis (RA). A 75-year-old Japanese woman had a 20-year history of RA and was found to have neutropenia and lymphocytosis by routine examinations. Her white cell count was 5,800/microl with 89% lymphocytes. The proliferating gammadelta-lymphocytes did not show the typical morphology of large granular lymphocytes (LGL) and were positive for CD3, TCRdelta1, and HLA-DR but negative for CD4, CD8, and deltaTCS1. Clonally rearranged TCRgamma-chain (Jgamma) and TCRbeta-chain (Cbeta1) genes were detected by Southern blot analysis. Clonality of these proliferating gammadelta-T cells was confirmed by CDR3 size analysis for the TCRdelta-chain. Anti-HTLV-I antibody was positive and the pX region of HTLV-I proviral dna was detected by PCR analysis, but clonal integration of HTLV-I proviral dna was not detected by Southern blotting analysis. The patient's clinical course has been stable, except for infrequent infectious episodes. The association of HTLV-I/II infection with T-LGL leukemia has been reported by several groups, although most cases exhibit TCRalphabeta type T cells. Analysis of the junctional sequence of TCR on T-LGL leukemia cells may clarify the role of HTLV-I/II infection in clonal T-cell proliferation.- - - - - - - - - - ranking = 1keywords = neutropenia (Clic here for more details about this article) |
2/38. CD3 , CD4-, CD8-, TCR alpha beta-, TCR gamma delta granular lymphocyte proliferative disorder without lymphocytosis and clinical symptoms.Granular lymphocyte-proliferative disorder is characterized by a proliferation of large granular lymphocytes (LGLs). It is often associated with neutropenia, rheumatoid arthritis (RA), and pure red cell aplasia (PRCA). Phenotypic analysis has demonstrated that in most cases, the LGLs show a clonal rearrangement of the TCR alpha beta rearrangement. We are reporting a patient with TCR gamma delta LGL proliferation without clinical findings and lymphocytosis. The patient showed an expansion of the CD3 , CD16 , CD56 , and CD57 LGL populations which involved coexpression of TCR gamma delta with TCR J gamma and J delta 1 gene rearrangement. Autoimmune manifestations, including RA and PRCA, have not appeared and the results of laboratory examinations have not changed for 1 year after the diagnosis.- - - - - - - - - - ranking = 0.16666666666667keywords = neutropenia (Clic here for more details about this article) |
3/38. Severe aplastic anemia associated with chronic natural killer cell lymphocytosis.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.- - - - - - - - - - ranking = 0.16666666666667keywords = neutropenia (Clic here for more details about this article) |
4/38. Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation.We report the case of a boy with hereditary spherocytosis who presented with mild microcytic hypochromic anemia and recurrent leg ulcers that had been present since childhood. Chronic natural killer (NK) cell and B-cell lymphocytosis was detected 1 year after therapeutic splenectomy during investigation of recurrent episodes of neutropenia and persistent lymphocytosis. NK cells proved to be abnormal at immunophenotyping studies, and B-cells were polyclonal and displayed a normal immunophenotype. Genotypic analysis of T-cell receptor (TCR)-beta and TCR-gamma genes showed a germ-line pattern. The clinical course of this patient was characterized by multiple pulmonary infections and amygdalitis. We discuss the potential roles of persistent immune stimulation due to chronic hemolysis and severe leg ulcers and of splenectomy in the origin of NK cell lymphocytosis and the relationship between NK cells and recurrent infections, relapsing neutropenia, and polyclonal B-cell response.- - - - - - - - - - ranking = 1keywords = neutropenia (Clic here for more details about this article) |
5/38. CD3 CD4-CD8 NK- large granular lymphocytosis with neutropenia and evidence for clonality and T-cell receptor gene rearrangement: two pediatric cases.The authors describe two pediatric cases of large granular lymphocytosis presenting early in the second decade of life with neutropenia and sepsis. They are among the youngest described in the literature. This report focuses on the advantages of detailed immunophenotypic and molecular analysis and highlights some of the controversies and uncertainties in the management of these patients, particularly the choice of immunosuppressive therapy. Immunosuppressive therapy in the two children described in this report resulted in improvement of neutropenia and clinical status, but this was not accompanied by the disappearance of the clonal population.- - - - - - - - - - ranking = 1keywords = neutropenia (Clic here for more details about this article) |
6/38. Case report: granulocyte colony-stimulating factor overcomes severe neutropenia of large granular lymphocytosis.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.- - - - - - - - - - ranking = 1.3333333333333keywords = neutropenia (Clic here for more details about this article) |
7/38. Unusual case of granular lymphocytes (GL) proliferation: simultaneous reactive and neoplastic proliferation.We report a case of a 55-year-old male with lymphoproliferative disease of granular lymphocytes. In the first year of follow-up reactive expansion of granular lymphocytes was observed during infectious episodes additionally to malignant proliferation. Histopathological studies revealed malignant lymphocytic infiltrations of the liver and gallbladder walls. The number of GL varied from 1.1 G/l to 17.8 G/l. immunophenotyping studies showed surface phenotype CD3 , CD8 . There was markedly reduced NK cell function. The patient exhibited lack of severe parenchymal involvement, moderately increased white cell count (up to 21.0 G/l), severe neutropenia (0.06 G/l - 0.8 G/l) and recurrent infectious episodes.- - - - - - - - - - ranking = 0.16666666666667keywords = neutropenia (Clic here for more details about this article) |
8/38. Large granular lymphocytosis terminating in a polymorphous B-lymphocytic proliferation after low-dose cyclophosphamide therapy: a case report with necropsy findings.A 70-year-old man presented with clonal large granular lymphocytosis of T-suppressor/cytotoxic immunophenotype, neutropenia, paraproteinemia, and proneness to infection. The patient became severely leukopenic during 14 days of chemotherapy with low-dose cyclophosphamide, and remained so after discontinuation of the drug. Clinically, he was thought to have prolonged chemotherapy-induced marrow hypoplasia. At death, 16 days after the last dose of chemotherapy, autopsy confirmed bone marrow hypoplasia and revealed that well-differentiated, polymorphous, and (immunophenotypically and genotypically) polyclonal b-lymphocytes predominated in normal hematopoietic and lymphoid organs. A similar lymphoid infiltrate was intimately associated with multiple ulcers and smooth muscle necrosis in the stomach. These terminal findings resemble B-lymphoproliferative conditions described in certain forms of immune deficiency.- - - - - - - - - - ranking = 0.16666666666667keywords = neutropenia (Clic here for more details about this article) |
9/38. Demonstration of clonality, by X-linked dna analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide.The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characteristics of either cytotoxic T lymphocytes (CD3 ,CD8 ) or natural killer (NK) cells (CD3-,CD15 ). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked dna analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked dna analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated magnetic beads. The dna of these cells was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy.- - - - - - - - - - ranking = 0.16666666666667keywords = neutropenia (Clic here for more details about this article) |
10/38. Childhood polyclonal T cell lymphocytosis with neutropenia: effects of antilymphocyte globulin and granulocyte colony stimulating factor in vitro and in vivo.The pathogenesis of the neutropenia that occurs in some patients with chronic T cell lymphocytosis is not well understood. We have investigated a 15-year-old girl with this syndrome. Initial committed bone marrow progenitor numbers (CFUgm) were low but markedly increased in vitro following T cell depletion. Similarly a transient correction of neutropenia was observed following in vivo lymphocyte depletion with antilymphocyte globulin. A sustained neutrophil recovery was achieved with daily therapy using recombinant human granulocyte colony stimulating factor (rhG-CSF) despite persistence of the lymphocytosis; during successful therapy CFUgm numbers remained low, and were not increased by the in vitro addition of rhG-CSF. These observations suggest the possibility of an inhibitory regulatory mechanism specifically acting on neutrophil granulopoiesis.- - - - - - - - - - ranking = 1keywords = neutropenia (Clic here for more details about this article) |
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