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)

Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are differentiated B-cell leukemias with well-described clinical, morphologic, and immunologic characteristics. We encountered two patients with indolent chronic B-cell leukemia showing overlapping features of these malignancies. The patients had progressive splenomegaly, minimal lymphadenopathy, and abnormal lymphoid cells with abundant cytoplasm and villi, which were strongly positive for surface antigens CD22 and CD11c, features associated with HCL. However, blood counts showed lymphocytosis without neutropenia and monocytopenia, and the bone marrow biopsies demonstrated tightly aggregated nodules of lymphocytes. In addition, the lymphoid cells were dual positive for CD19 and CD5, displaying weak-to-moderately positive monoclonal surface immunoglobulin, findings strongly suggestive of CLL. One patient failed to respond to therapy with chlorambucil and prednisone. The second patient showed a partial response to treatment with 2-chlorodeoxyadenosine. We compare our patients with similar variants of differentiated B-cell leukemias reported in the literature, including disorders described as hairy cell variant (HCL-V) or splenic lymphoma with villous lymphocytes (SLVL).
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PMID:CD5+ chronic B-cell leukemia with features intermediate to chronic lymphocytic leukemia and hairy cell leukemia. 752 21

One hundred immunocompromised HIV negative patients with microbiologically positive pneumonia underwent bronchoalveolar lavage (BAL) studies. Thirty cases showed peripheral neutropenia (< 1000 neutrophils/microL), 70 did not. The total cell number in BAL, the differential cell counts, and the lymphocyte subsets (CD4, CD8, CD19, CD57) were measured. Patients with pneumonia and normal or elevated peripheral neutrophils had a significantly increased total number of cells in BAL compared to patients with peripheral neutropenia (3.2 +/- 2 vs 1.3 +/- 0.6 x 10(5) cells/ml2 lavage fluid, p < 0.01). Ninety percent of the BAL differential cell counts obtained in patients exceeding 1000 neutrophils/microL showed a lymphocytic and/or neutrophilic alveolitis, whereas only 54% of patients with peripheral neutropenia displayed abnormal counts (p < 0.01). Yet the typical pattern of neutrophilic alveolitis was found more often for peripheral neutrophil counts over 1000/microL with high significance (p < 0.0001). Abnormal BAL cell patterns for neutropenic patients uniformly showed a lymphocytic alveolitis, only 10% additionally conformed with the pattern of neutrophilic alveolitis. Patients with pneumonia with and without peripheral neutropenia had similar findings in BAL lymphocyte subsets and exhibited a reduced CD4/CD8 ratio compared to controls (p < 0.05). The high susceptibility of severe neutropenic patients to pulmonary, especially fungal infections may be explained by the local lack of neutrophils.
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PMID:Differential cell count and lymphocyte subsets in bronchoalveolar lavage during pneumonia with and without peripheral neutropenia. 777 4

The clinical application of recombinant human G-CSF in patients with acute myeloid leukemia (AML) has been controversial because it stimulates the in vitro proliferation of leukemic cells. In order to explore the possibility of predicting in vivo leukemic proliferation after G-CSF administration to AML patients by using in vitro assays, we investigated the leukemic blasts of 30 AML patients, including 14 patients who received G-CSF for severe infection associated with neutropenia following chemotherapy (G-CSF group) and 16 patients who did not (control group). Of the 14 patients in the G-CSF group, 9 showed an increase of leukemic blasts in the peripheral blood during G-CSF administration, while 11 of the 16 control patients developed leukemic resurgence. In the G-CSF group, the frequency of leukemic resurgence among patients whose blasts showed dose-dependent proliferation after addition of G-CSF to cultures was similar to that among patients whose blasts did not. In addition, there were no significant differences between the G-CSF and control groups in [3H]thymidine incorporation by leukemic cells and leukemic colony formation after the addition of G-CSF to cultures. The G-CSF receptor affinity of leukemic blasts was significantly higher in the patients with leukemic resurgence (mean dissociation constant [Kd]: 55 pM in the G-CSF group and 63 pM in the control group) than in those without it (101 pM and 96 pM, respectively), and the number of G-CSF receptors per cell was significantly lower when leukemic resurgence occurred (200 in the G-CSF group and 260 in the control group) than when it did not (3400 and 3030, respectively). Immunophenotyping (for CD2, CD7, CD10, CD13, CD19, CD33, CD34, CD71, HLA-DR, glycophorin A and the G-CSF receptor) revealed no significant differences between blasts from the patients with and without leukemic resurgence in the G-CSF group. Thus, we conclude that the in vivo leukemic resurgence during G-CSF administration after chemotherapy for AML was not correlated with the in vitro responsiveness of leukemic blasts to this cytokine or with blast phenotyping data. Leukemic resurgence is likely to occur in patients whose leukemic blasts have fewer numbers of G-CSF receptors with a high affinity irrespective of whether patients receive G-CSF.
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PMID:Granulocyte colony-stimulating factor in acute myeloid leukemia. 859 Aug 66

A clinical goal for ex vivo expansion of cord blood (CB) CD34(+) cells is to shorten the period of neutropenia and thrombocytopenia following myeloablative therapy and transplantation. Prolongation of cytokine expansion leads to the production of greater numbers of cells, and should have an impact on neutrophil and platelet recovery. Furthermore, expansion of CD34(+) cells should support the continued production of neutrophils and platelets in the 6-week period following transplantation. We tested these hypotheses by characterization of the kinetics (human CD45(+) cells in the blood) and phenotype (CD45, CD34, CD61, CD33, CD19 and CD3) of human engraftment in the non-obese diabetic severe combined immunodeficient mouse (NOD-SCID) following 7 or 14 d of ex vivo expansion of CB CD34(+) cells. Mice transplanted with 14 d cells showed greater percentages of human CD45(+) cells in the blood, bone marrow and spleen than mice transplanted with unexpanded cells or 7 d cells. Prolonging cytokine exposure of CD34(+) cells and transplantation with increasing numbers of input cells facilitated the production of absolute numbers of CD34(+), CD33(+), CD61(+) and CD19(+) cells in vivo. Furthermore, analysis of SCID engrafting potential showed that prolongation of culture duration facilitates in vivo expansion of CD45(+), CD34(+) and CD19(+) cells after transplantation. It is anticipated that prolonged (2 weeks) ex vivo culture of CB will have a beneficial clinical effect.
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PMID:Prolonged ex vivo culture of cord blood CD34(+) cells facilitates myeloid and megakaryocytic engraftment in the non-obese diabetic severe combined immunodeficient mouse model. 1152 68

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

A 3-year-old Turkish boy with a history of chronic cough, recurrent bronchopneumonia, and a borderline sweat chloride test (40 mEq/L) was referred for further evaluation to our department. He was born at term (2100 g) to a marriage with no consanguinity. His mother and father were 40 and 46 years old, respectively. Physical examination (Fig. 1) revealed hypopigmented, atrophic, and hyperkeratotic skin lesions surrounded by reticulate hyperpigmentation on the entire body, predominantly on the face, neck, arms, shoulders, and legs, which had been noticed initially at the age of 18 months. Dystrophic toenails, sparse and thin hair, and phimosis were also observed. Laboratory tests disclosed an isolated neutropenia (white blood cell count, 1800/mm3). Bone marrow (BM) aspiration showed a decreased myelopoiesis without myelodysplastic changes, but normal erythropoiesis, megakaryopoiesis, and normal stroma. Lymphocyte subgroups containing CD4, CD5, CD6, CD8, CD19, CD23, and CD25, and immunoglobulin G (IgG), IgM, IgA, and IgE, were in the normal range; hemoglobin F (HbF), 2.8%. Spontaneous and clastogen-induced chromosome breaks were not increased. A skin biopsy showed increased pigmentation at the basal layer, dyskeratotic epidermal cells, and marked IgM deposition and cytoid bodies and mild IgA and IgG deposits at the dermo-epidermal junction. Lactate response to glucose challenge, amino acid chromatography, and urine organic acid analysis were normal. A diagnosis of dyskeratosis congenita (DC) was made with typical skin lesions, dystrophic toenails, thin and sparse hair, and neutropenia with decreased myelopoiesis in BM. Treatment with granulocyte colony-stimulating factor (G-CSF) was considered for the neutropenia. As the increase in neutrophil count at a dose of 5 microg/kg was not adequate, 10 microg/kg G-CSF was tried (Fig. 2). With 10 microg/kg once to three times a week, a 1.8-4.8-fold increase in the absolute neutrophil count (ANC) was achieved with no side-effects. Treatment was more frequent during infection (days 22-28).
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PMID:Dyskeratosis congenita with isolated neutropenia and granulocyte colony-stimulating factor treatment. 1201 Mar 44

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

Hairy cell leukemia is an indolent, chronic B-cell lymphoproliferative disorder comprising approximately 2 to 3% of all adult leukemias in the United States. Hairy cells are clonal expansions of mature, activated B-cells. They co-express CD11c, CD19, CD20, CD22, CD25, and CD103. Hairy cells possess clonal immunoglobulin gene rearrangements and express monoclonal surface immunoglobulin of either IgG or multiple heavy-chain isotypes. Treatment of hairy cell leukemia should be considered for symptomatic patients. It is indicated in patients with significant neutropenia, anemia, thrombocytopenia, symptomatic splenomegaly, constitutional symptoms due to hairy cell leukemia, or recurrent serious infections. Many treatments exist, including cladribine, pentostatin, interferon-alpha, splenectomy, rituximab (mabthera), and BL-22 immunotoxin.
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PMID:Hairy cell leukemia: an update. 1279 30

Patients with dysmorphic disorders seem to have frequent respiratory infections that may be attributed to associated anatomic or neurological abnormalities, but immune defects may contribute to their susceptibility to infections. We screened subjects with dysmorphic conditions for major hematologic, B-cell and T-cell defects. We studied 84 subjects with dysmorphic disorders: 29 with chromosomal disorders, 27 with single gene disorders, and 28 with unclassified dysmorphic disorders. They were evaluated by physical examination; medical history suggestive of possible immune deficiency; complete blood count; serum immunoglobulin G (IgG), IgA, and IgM levels; and lymphocyte subsets. Low laboratory values (less than fifth percentile for age) were detected in 54.8%; was highest in the chromosomal disorder group (79.3%) followed by the single gene disorder group (55.6%) and was lowest in the unclassified dysmorphic disorder group (28.6%). The most common low values were in the CD19 and CD16/56 lymphocyte subpopulations followed by IgG and IgA levels. None of the subjects had neutropenia or thrombocytopenia. History of significant recurrent infections was noted in five subjects, all of whom had abnormal laboratory values. The highest frequency of abnormal laboratory values was in Down syndrome followed by Turner syndrome and chromosome deletions. We concluded that patients with dysmorphic disorders, particularly those with chromosomal disorders, have a high frequency of various B-cell and T-cell defects that may be contributing to their susceptibility to infection. Studies are needed to further delineate the immunologic defects in that population and to investigate a possible genetic basis at the molecular level.
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PMID:Immune defects in subjects with dysmorphic disorders. 1645 May 72

Chediak - Higashi Syndrome (CHS) is a rare, primary Immunodeficiency disorder with an autosomal recessive (AR) inheritance and characterized by recurrent infection, partial occulocutaneous albinism and an accelerated phase.In this report we describe clinical and laboratory findings from 6 CHS patients. Clinical and laboratory information of six patients who were referred to our center during the last 20 years (from 1983 - 2003) were reviewed.Onset age of disease was between 3 months to 10 years. All patients had history of consanguineous parents and two patients were siblings. All patients had oculocutaneous albinism, nystagmus, recurrent infections which included upper and lower respiratory tract (U and LRT) infections, stomatitis, thrush, and skin abscesses and hepatitis. In laboratory findings, all patients had neutropenia and normal immunoglobulins and normal CD3, CD4, CD8 and CD19 lymphocyte by flowcytometry and three of the four patients had chemotatic defect. Five patients certainly had giant granule in bone marrow neutrophil and in one patient it was equiovocal. Three patients had an accelerated phase, and for one patient bone marrow transplantation was done that was tolerated well and had been well after 7 years.We emphasize the need for early diagnosis on basis of characteristic facies and diagnostic laboratory examinations and early bone marrow transplantation (BMT) in patients.
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PMID:Report of six cases of chediak-higashi syndrome with regard to clinical and laboratory findings. 1730 79


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