Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A therapeutic trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was attempted in a patient with neutropenia and frequent infections secondary to T-gamma lymphoproliferative disease (T-gamma LPD). During the 14 days of subcutaneous rhGM-CSF (500 micrograms/m2/day), the absolute eosinophil count increased from 0 to 9,455/microliters. By contrast, the absolute neutrophil count decreased. Toxicity related to rhGM-CSF included arthralgia and nonspecific chest pain. The possible mechanism for the rhGM-CSF induced selective eosinophilia is discussed.
 ...
PMID:Eosinophilia resulting from administration of recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in a patient with T-gamma lymphoproliferative disease. 201 68

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.
 ...
PMID:Neutropenia associated with T-cell large granular lymphocyte leukemia: long-term response to cyclosporine therapy despite persistence of abnormal cells. 955 95

Chronic neutropenia with autoimmune diseases is associated mainly with rheumatoid arthritis (RA), as Felty's syndrome or large granular lymphocyte (LGL) leukemia, and with systemic lupus erythematosus (SLE). Recent advances have allowed better understanding regarding the mechanism of neutropenia and improved options for treatment. Target antigens for antineutrophil antibodies have been identified for both Felty's syndrome and for SLE. The role of soluble Fas-ligand (FasL) in inducing apoptosis of neutrophils has been clarified for LGL leukemia and increased neutrophil apoptosis has been described in neutropenic patients with SLE. The role of immune complexes in affecting neutrophil traffic and function continues to be studied. Treatments of neutropenia have included methotrexate, cyclosporine A, and granulocyte colony-stimulating factor (G-CSF) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). The efficacy of both GM- and G-CSF in reversing neutropenia and decreasing the risk of infections in Felty's syndrome and SLE has been well documented. Of concern, however, have been flares of symptoms or development of leukocytoclastic vasculitis in some patients following the use of these cytokines. Recent results suggest that in these patients G-CSF should be administered at the lowest dose effective at elevating the neutrophil count above 1,000/microL.
 ...
PMID:Chronic neutropenia associated with autoimmune disease. 1195 95