1/54. Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors.Myelokathexis is a congenital disorder that causes severe chronic leukopenia and neutropenia. Characteristic findings include degenerative changes and hypersegmentation of mature neutrophils and hyperplasia of bone marrow myeloid cells. The associated neutropenia can be partially corrected by treatment with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These features led us to propose that accelerated apoptosis of neutrophil precursors might account for the neutropenic phenotype. Blood and bone marrow aspirates were obtained from 4 patients (2 unrelated families) with myelokathexis before G-CSF therapy and from 2 of the affected persons after G-CSF therapy (1 microg/kg per day subcutaneously for 3 weeks). Bone marrow was fractionated using immunomagnetic bead cell sorting into CD34( ), CD33( )/CD34(-), and CD15( )/CD34(-)/CD33(- )cell populations. Examination of these cells by flow cytometry and electron microscopy revealed abundant apoptosis in the CD15( ) neutrophil precursor population, characterized by enhanced annexin-V binding, extensive membrane blebbing, condensation of heterochromatin, and cell fragmentation. Colony-forming assays demonstrated significant reduction in a proportion of bone marrow myeloid-committed progenitor cells. Immunohistochemical analysis revealed a selective decrease in bcl-x, but not bcl-2, expression in the CD15( )/CD34(-)/CD33(-)cell population compared with similar subpopulations of control bone marrow-derived myeloid precursors. After G-CSF therapy, apoptotic features of patients' bone marrow cells were substantially reduced, and the absolute neutrophil counts (ANC) and expression of bcl-x in CD15( )/CD34(-)/CD33(-)cells increased. The authors concluded that myelokathexis is a disease characterized by the accelerated apoptosis of granulocytes and the depressed expression of bcl-x in bone marrow-derived granulocyte precursor cells. These abnormalities are partially corrected by the in vivo administration of G-CSF. (Blood. 2000;95:320-327)- - - - - - - - - - ranking = 1keywords = flow (Clic here for more details about this article) |
2/54. Inverse relation between plasma G-CSF levels and neutrophil counts in a patient with autoimmune neutropenia treated with G-CSF.The pharmacokinetic characteristics of granulocyte colony-stimulating factor (G-CSF) appears to be related to the neutrophil count. We report the case of an 81-year-old male with acquired antibody induced neutropenia treated with G-CSF. This produced a rapid increase in the neutrophil count which appeared to be associated with diminished trough plasma G-CSF levels. Our data appears to indicate that mature neutrophils may play a part in the clearance of G-CSF from plasma.- - - - - - - - - - ranking = 31.359330094206keywords = plasma (Clic here for more details about this article) |
3/54. Chronic neutropenia: Response to plasma with high colony-stimulating activity.A child with repeated infections was immunologically normal but was found to have neutropenia with periodic elevations of the absolute mature polymorphonuclear count at 21-day intervals. Immediately following the PMN rise, bone marrow morphology and in vitro cultures demonstrated a maturation arrest at the myelocyte stage with an increase in proliferative capacity. His cycle was not altered by infusions of normal plasma or by injections of epinephrine or typhoid vaccine. Infusion of 10 ml/kg of "stimulated" plasma from donors reactive to TV, obtained 60 minutes following immunization, resulted in an out-of-phase rise in PMN cells and clinical improvement. in vitro assays, using normal or patient marrow, detected high levels of colony-stimulating activity only in those plasma samples that were effective in the patient. These observations support a role of CSA as a physiologic regulator of granulopoiesis in man.- - - - - - - - - - ranking = 36.585885109906keywords = plasma (Clic here for more details about this article) |
4/54. Alteration of colony-stimulating factor output, endotoxemia, and granulopoiesis in cyclic neutropenia.Cellular and humoral factors involved in the regulation of granulopoiesis were evaluated in two patients with cyclic neutropenia by utilizing the agar-gel marrow culture technique to serially study marrow granulocytic colony-forming capacity (CFC) and the urinary output of colony-stimulating factor (CSF). CSF output varied inversely with peripheral neutrophil counts and directly with monocyte counts and evidence for infection (endotoxemia and/or staphylococcal abscesses). Following autologous infusion of one patient's plasma obtained during a period of neutropenia, increased urinary excretion of CSF occurred concomitant with increments in both marrow CFC and the proportion of granulocytic progenitor cells in dna synthesis. Neutrophil periodicity was not altered by the administration of the neutropenic plasma. These findings are consistent with the hypothesis that cyclic neutropenia is caused by a quantitatively decreased entry of stem cells or granulocytic progenitor cells into granulopoiesis.- - - - - - - - - - ranking = 10.453110031402keywords = plasma (Clic here for more details about this article) |
5/54. G-CSF plasma levels in clozapine-induced neutropenia.BACKGROUND: Clinical reports emphasize the therapeutic usefulness of granulocyte colony-stimulating factor (G-CSF) in clozapine-induced granulocytopenia. Only sparse information exists, however, on the natural course of endogenous G-CSF plasma levels in this condition. methods: We monitored G-CSF and white blood cell (WBC) counts in a 73-year-old patient who developed granulocytopenia while being treated with clozapine for schizoaffective disorder. clozapine treatment was discontinued immediately, and G-CSF serum levels were determined repeatedly during the clinical course. RESULTS: Whereas WBC counts increased again within 6 days after discontinuation of clozapine, G-CSF level decreased significantly within the same period. The rapid decrease of endogenous G-CSF levels paralleled by a normalization of neutrophil count was interpreted as the result of an intact regulatory mechanism of granulocytopoesis. Therefore G-CSF therapy was not initiated. Owing to lack of therapeutic alternatives, it was decided to reintroduce clozapine. G-CSF levels decreased further, accompanied by an increase of WBCs, indicating stable bone marrow functioning. CONCLUSIONS: Based on this observation, we assume that the course of G-CSF and WBC counts indicated an abortive form of toxic bone marrow damage with subsequent recovery. We conclude that monitoring of G-CSF levels may serve as a useful tool in the follow-up of patients in whom clozapine-induced bone marrow damage is suspected.- - - - - - - - - - ranking = 26.132775078505keywords = plasma (Clic here for more details about this article) |
6/54. Large granular lymphocyte leukemia: case report of chronic neutropenia and rheumatoid arthritis-like symptoms in a child.lymphoproliferative disorders of large granular lymphocytes (LGL) are heterogeneous, with a clinical/pathologic spectrum ranging from a benign polyclonal expansion to an aggressive clonal disease. Often these lymphoproliferative disorders are associated with autoimmune disease. The clonal form of the disorder, LGL leukemia, typically occurs in older adults with a median age of 55 years at diagnosis. Pediatric cases are referred to in review articles; however, no detailed reports of T-cell LGL leukemia in children exist. This report illustrates a case of a child who presented initially at age 2 and 1/2 years with psoriasis, juvenile rheumatoid arthritis-like symptoms, and neutropenia. Bone marrow examinations obtained throughout his course have demonstrated progressive hypercellularity with increased reticulin fibers and replacement of the normal marrow elements by lymphocytes, which were later identified as large granular lymphocytes. Further testing with immunophenotyping by flow cytometry and T-cell receptor gene rearrangement studies revealed a monoclonal proliferation of large granular lymphocytes and confirmed a diagnosis of LGL leukemia. Although rare, large granular lymphocyte leukemia should be included in the differential diagnosis of chronic neutropenia in children.- - - - - - - - - - ranking = 1keywords = flow (Clic here for more details about this article) |
7/54. Autoimmune neutropenia with cyclic oscillation of neutrophil count after steroid administration.A 16-year-old female patient was evaluated for pancytopenia. She had a white blood cell count of 1.6 x 10(9)/L with 0.02 neutrophils and a platelet count of 19 x 10(9)/L. In the bone marrow, mature granulocytes were markedly decreased in number, but no atypical cells were present. Antineutrophil antibody was demonstrated by flow cytometry, and the level of platelet-associated immunoglobulin g was increased. A diagnosis of autoimmune neutropenia and thrombocytopenia was made. Interestingly, neutrophil and platelet counts fluctuated cyclically after the initiation of prednisolone therapy. The neutrophil count fluctuated between 0.1 x 10(9)/L and 7 x 10(9)/L, and the platelet count fluctuated between 19 x 10(9)/L and 175 x 10(9)/L, in 4-week cycles. Following splenectomy, neutrophil and platelet counts normalized. We believe the immune mechanism of recurrent neutropenia in this patient differs from that in other patients with cyclic neutropenia reported with stem cell disorders.- - - - - - - - - - ranking = 1keywords = flow (Clic here for more details about this article) |
8/54. A possible role for maternal HLA antibody in a case of alloimmune neonatal neutropenia.BACKGROUND: Alloimmune neonatal neutropenia (ANN) is caused by a reaction of maternal alloantibodies with paternally inherited antigens on the fetal neutrophils. While human neutrophil antigens (HNA) antibodies are found in half of ANN cases, specific antibodies have not been defined in the remaining cases. STUDY DESIGN AND methods: Reported here is a neonate with omphalitis due to neutropenia. To elucidate the cause of ANN, flow cytometric and PCR analyses were used. Reactions of the patient's and mother's sera with neutrophils, lymphocytes, and platelets were examined by lymphocytotoxicity test (LCT), anti-human immunoglobulin-LCT, and mixed passive hemagglutination test. RESULTS: The maternal sera reacted with neutrophils, lymphocytes, and platelets of the patient and father. The platelet adsorption eliminated the reaction of the maternal serum with the patient's neutrophils. The HLA typing of the family and an LCT using a panel of lymphocytes of 20 HLA-typed donors showed hla-a2 antigen as a target of antibodies in the maternal serum. According to anti-human immunoglobulin-LCT, the anti-HLA-A2 was present in the neonatal serum. On the other hand, HNA antibodies were not detectable in the patient's or the mother's serum. CONCLUSION: These results suggest that the transplacental passage of the maternal HLA antibody caused neutropenia in this patient.- - - - - - - - - - ranking = 1keywords = flow (Clic here for more details about this article) |
9/54. pharmacokinetics of paclitaxel and cisplatin in a hemodialysis patient with recurrent ovarian cancer.This is the first report that the combination of paclitaxel and cisplatin is feasible in a patient with recurrent ovarian cancer undergoing hemodialysis. paclitaxel at a dose of 150 mg/m(2) was administered as a 3-h continuous i.v. infusion. Thirty minutes after paclitaxel administration, cisplatin was administered at a dose of 30 mg/m(2) for 30 min. Hemodialysis was started 30 min after completion of the cisplatin infusion and performed for 5 h. The maximum plasma concentrations of paclitaxel, total platinum and free platinum were 3.26, 2.44 and 1.84 microg/ml, respectively. The AUC of paclitaxel and free platinum were 15.3 and 1.76 microg x h/ml, respectively. The pelvic tumor size was reduced by 42% on MRI after the second course of this therapy. Grade IV neutropenia and grade III thrombopenia were observed. We conclude that paclitaxel and cisplatin combination chemotherapy is efficacious and feasible for an ovarian cancer patient under hemodialysis.- - - - - - - - - - ranking = 5.2265550157009keywords = plasma (Clic here for more details about this article) |
10/54. "T-cell-rich B-cell lymphoproliferative disorder" of the bone marrow.We report four cases of a "T-cell-rich B-cell chronic lymphoproliferative disorder" involving the bone marrow and not extramedullary sites. The neoplastic B-cell proliferation in these cases was composed predominantly of small lymphoid cells with features of both hairy cell leukemia and lymphoplasmacytoid lymphoma. All cases presented with neutropenia and with difficulty in diagnosis. We present the clinical, morphologic, cytochemical, and immunophenotypic findings in these cases and discuss this entity.- - - - - - - - - - ranking = 5.2265550157009keywords = plasma (Clic here for more details about this article) |
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