Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia.
(65/995)
A prospective multicenter trial of 119 children 1 to 18 years of age with newly diagnosed aplastic anemia (AA) was conducted, comparing treatment using antithymocyte globulin (ATG), cyclosporine (CyA), and danazol (DAN) with or without rhG-CSF (400 microg/m(2), day on days 1-90). All children with very severe AA received rhG-CSF (VSAA group, n = 50). The other children were randomized to receive ATG, CyA, DAN, and rhG-CSF (G-CSF+ group, n = 35) or ATG, CyA, and DAN without rhG-CSF (G-CSF- group, n = 34). After 6 months, the hematologic response rate was 71%, 55%, and 77% in the VSAA group, G-CSF+ group, and G-CSF- group, respectively. There was no difference in the incidence of febrile episodes and documented infections between the G-CSF+ and G-CSF- groups. Bone marrow transplantation (BMT) was attempted in 22 patients in whom initial immunosuppressive therapy (IST; n = 18) failed or in whom a relapse occurred after an initial response (n = 4). Nineteen of the 22 patients are alive and well after a median follow-up of 18 months (range, 3 to 66 months) since BMT. The probability of survival at 4 years was 83% +/- 7% in the VSAA group, 91% +/- 5% in the G-CSF+ group, and 93% +/- 6% in the G-CSF- group. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) developed in one patient in each of the three groups; the overall risk for MDS/AML was 3% +/- 2% at 4 years. Because the results of IST were encouraging, it is suggested that children with AA receive IST as first-line therapy if there is no human leukocyte antigen-matched sibling donor. (+info)
Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin.
(66/995)
Paroxysmal nocturnal hemoglobinuria (PNH) is caused by a somatic mutation in the gene PIGA, which encodes an enzyme essential for the synthesis of glycosylphosphatidylinositol (GPI) anchors. The PIGA mutation results in absence or marked deficiency of more than a dozen proteins on PNH blood cells. Current flow cytometric assays for PNH rely on the use of labeled antibodies to detect deficiencies of specific GPI anchor proteins, such as CD59. However, because no single GPI anchor protein is always expressed in all cell lineages, no one monoclonal antibody can be used with confidence to diagnose PNH. We describe a new diagnostic test for PNH, based on the ability of a fluorescently labeled inactive variant of the protein aerolysin (FLAER) to bind selectively to GPI anchors. We compared GPI anchor protein expression in 8 patients with PNH using FLAER and anti-CD59. In all cases, FLAER detected similar or higher proportions of PNH monocytes and granulocytes compared with anti-CD59. Because of the increased sensitivity of detection, FLAER could detect small abnormal granulocyte populations in patients to a level of about 0.5%; samples from healthy control subjects contained substantially fewer FLAER-negative cells. FLAER gives a more accurate assessment of the GPI anchor deficit in PNH. (+info)
F-cells in the adult: normal values and levels in individuals with hereditary and acquired elevations of Hb F.
(67/995)
Specific antibodies to human fetal hemoglobin were prepared and, after conjugation with a fluorescent dye, were used to determine the distribution of Hb F-containing cells in blood smears from normal adults and individuals with hereditary and acquired conditions associated with abnormal levels of Hb F. The mean proportion of F-cells in normal persons was 2.7% +/- 1.4%, with a range of 0.5%-7.0%. Proportions of F-cells were increased in persons with several acquired and inherited disorders that are associated with an increased percentage of Hb F in hemolysates. A strong linear correlation between the amount of Hb F and proportion of F-cells was observed. This technique may prove useful in studies of a variety of disorders associated with Hb F elevations and also in investigations of the mechanisms controlling the transition from fetal to adult hemoglobin during the course of human development. (+info)
Hematopoietic progenitor cells in the blood and bone marrow in various hematologic disorders.
(68/995)
Hematopoietic progenitor cells are present in the blood and the bone marrow. Changes in the numbers of hematopoietic progenitor cells reflect alteration of pluripotent stem cells. We discuss such changes in common hematologic diseases including aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) and thalassemia. In aplastic anemia, the numbers of burst forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) are much decreased; the decrease still exists after recovery from therapy. In PNH, the numbers of progenitor cells are low, even in the presence of marrow hypercellularity. In thalassemia, the numbers of progenitor cells are much increased; more pronounced in splenectomized patients. (+info)
Cell dose and speed of engraftment in placental/umbilical cord blood transplantation: graft progenitor cell content is a better predictor than nucleated cell quantity.
(69/995)
There is evidence that the total cellular content of placental cord blood (PCB) grafts is related to the speed of engraftment, though the total nucleated cell (TNC) dose is not a precise predictor of the time of neutrophil or platelet engraftment. It is important to understand the reasons for the quantitative association and to improve the criteria for selecting PCB grafts by using indices more precisely predictive of engraftment. The posttransplant course of 204 patients who received grafts evaluated for hematopoietic colony-forming cell (CFC) content among 562 patients reported previously were analyzed using univariate and multivariate life-table techniques to determine whether CFC doses predicted hematopoietic engraftment speed and risk for transplant-related events more accurately than the TNC dose. Actuarial times to neutrophil and platelet engraftment were shown to correlate with the cell dose, whether estimated as TNC or CFC per kilogram of recipient's weight. CFC association with the day of recovery of 500 neutrophils/microL, measured as the coefficient of correlation, was stronger than that of the TNC (R = -0.46 and -0.413, respectively). In multivariate tests of speed of platelet and neutrophil engraftment and of probability of posttransplantation events, the inclusion of CFC in the model displaced the significance of the high relative risks associated with TNC. The CFC content of PCB units is associated more rigorously with the major covariates of posttransplantation survival than is the TNC and is, therefore, a better index of the hematopoietic content of PCB grafts. (Blood. 2000;96:2717-2722) (+info)
Veno-occlusive disease of the liver after allogeneic bone marrow transplantation for severe aplastic anemia.
(70/995)
There are few reports about the occurrence of hepatic VOD after BMT for severe aplastic anemia (SAA). We prospectively studied 17 patients with SAA after allogeneic BMT for the occurrence and severity of VOD. Plasma levels of protein C, protein S, antithrombin III, vWF, t-PA and PAI-1 were determined before preparative chemotherapy, on the day of marrow infusion, and on days 7, 14 and 21. VOD occurred in seven patients (41.2%) at a median of day 1 (range, day -2 to 15). Five had mild, and two moderate VOD. Platelet transfusion requirements were higher in the patients with VOD. The plasma levels of natural anticoagulants such as protein C, free protein S and antithrombin III decreased significantly on day 0 from the baseline levels. Plasma levels of t-PA, PAI-1 and vWF increased significantly in the early post-transplant period compared to the baseline levels. The mean plasma levels of t-PA on day 7 (P = 0.016) and PAI-1 on days 0 and 7 (P = 0.016, 0.032) were higher in the patients with VOD. In summary, we observed hypercoagulability and a high incidence of VOD after allogeneic BMT for SAA. Levels of t-PA and PAI-1 were significantly higher in the patients with VOD after BMT. (+info)
Aplastic crisis caused by parvovirus B19 in an adult patient with sickle-cell disease.
(71/995)
We describe a case of aplastic crisis caused by parvovirus B19 in an adult sickle-cell patient presenting with paleness, tiredness, fainting and dyspnea. The absence of reticulocytes lead to the diagnosis. Anti-B19 IgM and IgG were detected. Reticulocytopenia in patients with hereditary hemolytic anemia suggests B19 infection. (+info)
Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia.
(72/995)
Lymphoproliferative disease of granular T lymphocyte (T-LDGL), also known as T-cell large granular lymphocyte leukemia, is a clonal disorder of cytotoxic T lymphocytes that is clinically manifested as chronic neutropenia and anemia. Association with autoimmune disorders is common. In 9 patients, T-LDGL is reported as presenting as aplastic anemia. The clinical characteristics were similar to acquired aplastic anemia. Morphologic evidence of increased granular lymphocytes in the peripheral blood and an excess of CD3(+)/CD8(+)/CD57(+) cells in the bone marrow were found in most cases. Cyclophosphamide was ineffective, but noncytotoxic immunosuppressive agents generally produced a good response. After a median follow-up of 49 months, 5 patients had died from the disease or related complications. Median survival was 40 months. Aplastic anemia can be a presenting manifestation of T-LDGL, and T-LDGL should be considered in the differential diagnosis of acquired aplastic anemia. (+info)