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)

We report severe aplastic anemia of neonatal onset diagnosed in six girls between 1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six), and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x 10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age and in all patients by 1 year of age. Lymphocyte number and functions were normal. In all children bone marrow biopsy showed hypocellularity for age and absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic abnormalities. Blood and medullary cytogenetic studies were normal. A search for known constitutional, viral, or toxic causes was negative. Immunosuppressive therapy failed to restore hematopoiesis (three of six). Five children received a bone marrow transplantation at an average age of 9 months (range 2.7 to 29 months). One child is alive and well after a human leukocyte antigen-identical bone marrow transplantation, whereas the other four died. Both congenital onset and the high rate of familial involvement suggest that this condition may be inherited.
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PMID:Severe aplastic anemia of neonatal onset: a single-center retrospective study of six children. 958 Jul 48

The atypical antipsychotic agent clozapine is known to be effective in schizophrenic patients refractory to other medications; however, it induces agranulocytosis in approximately 1-2%. In Jews, this complication is associated with the haplotype HLA B38,DR4,DQ3. The aim of the present study was to determine which human leukocyte antigen (HLA) antigens are involved in clozapine-induced agranulocytosis. We performed HLA typing in 88 Jewish Israeli schizophrenic patients and in 127 ethnically matched healthy individuals. Thirty-eight patients responsive to standard antipsychotic medications were treated with haloperidol, and 50 refractory patients received clozapine. A trend was noted for elevated rates of HLA B38 among control individuals and clozapine-treated patients of Ashkenazi origin compared to individuals of non-Ashkenazi origin, but the findings failed to reach statistical significance. No association was found between HLA class I antigens and the response to haloperidol or clozapine. Neutropenia developed in two clozapine-treated patients and agranulocytosis in one. Two of these three patients were of Ashkenazi origin, and both demonstrated the HLA B38 phenotype. Although the findings did not reach a statistical significance because of the small number of patients, they may support an association between clozapine-induced neutropenia/agranulocytosis and Ashkenazi origin and the HLA B38 phenotype. The rate of agranulocytosis in our sample (2%) is similar to the usual cumulative risk of agranulocytosis but in contrast to its high frequency among Jewish American patients. One possible explanation for this difference is the high rate of Ashkenazi patients in the American sample and the preponderance of non-Ashkenazi patients in our population.
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PMID:Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in jewish Israeli schizophrenic patients. 1052 73

The optimal approach for stem cell transplantation in children with immunodeficiency has yet to be determined. Conditioning therapy is necessary for reliable engraftment and full immune reconstitution; however, the beneficial effect of cytoreductive conditioning is counterbalanced by increased short- and long-term treatment-related toxicity. Whether bone marrow transplantation with a nonmyeloablative preparative regimen was sufficient for the establishment of donor immune reconstitution, with the resultant correction of disease phenotype, was investigated. Eight patients with severe immunodeficiency states underwent T-cell replete bone marrow transplantation from a human leukocyte antigen-matched unrelated (n = 6) or sibling (n = 2) donor with nonmyeloablative conditioning using a fludarabine-melphalan-anti-lymphocyte globulin-based regimen. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. All patients were engrafted with predominantly donor hematopoiesis, and the duration of neutropenia was brief. Significant acute graft-versus-host disease (GVHD) did not develop, but one patient had limited chronic GVHD. One patient died of disease recurrence, and 3 have stable, mixed chimerism. At a median follow-up of 1 year, all patients have had good recovery of CD3(+) T-cell numbers, and 6 of 7 evaluable patients have normal phytohemagglutinin stimulation indices. The rate of immune reconstitution is comparable with that of historical controls undergoing standard myeloablative protocols. Two patients with CD40 ligand deficiency now show significant expression, and a patient with adenosine deaminase deficiency has improved deoxy adenosine triphosphate metabolites. In summary, it has been demonstrated that nonmyeloablative stem cell transplantation permits rapid engraftment from both sibling and unrelated donors with minimal toxicity even in the presence of severe organ dysfunction. If long-term immune reconstitution of patients treated with this protocol is demonstrated, it is believed this approach might offer significant advantages compared with standard protocols by combining adequate immune reconstitution with reduced short- and long-term toxicity. (Blood. 2000;96:1239-1246)
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PMID:Nonmyeloablative stem cell transplantation for congenital immunodeficiencies. 1094 63

Olanzapine is an atypical antipsychotic medication frequently used in the management of psychotic states. While it has proved to be safe compared to clozapine with regard to haematotoxicity, because it has only been available for a few years, full documentation of its haematological side-effects remains incomplete. We report a case of olanzapine-induced leukopenia with associated neutropenia. Since clozapine-induced haematotoxicity has been associated with characteristic human leukocyte antigen (HLA) groups, HLA typing was determined in this patient. Following failure with typical antipsychotic medication, the patient received 10 mg/day of olanzapine. Three weeks later, he developed fever and a significant decrease in leukocyte count. Olanzapine was immediately discontinued. HLA typing was determined. The white cell count returned to normal and the fever, most probably secondary to the low white cell count, subsided with antibiotic treatment. HLA typing results were: A1 24, B7, B35, DRB1*15, DRB1*11, DRB3*01-03, DRB5*01-02. Olanzapine may induce serious leukopenia and neutropenia. HLA typing in this single patient demonstrated a distinct haplotype compared to that previously observed in clozapine-induced haematoxicity.
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PMID:Olanzapine-induced leukopenia with human leukocyte antigen profiling. 1119 61

The incidence of postengraftment invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients increased during the 1990s. We determined risks for IA and outcomes among 1682 patients who received HSCTs between January 1993 and December 1998. Risk factors included host variables (age, underlying disease), transplant variables (stem cell source), and late complications (acute and chronic graft-versus-host disease [GVHD], receipt of corticosteroids, secondary neutropenia, cytomegalovirus [CMV] disease, and respiratory virus infection). We identified risk factors associated with IA early after transplantation (<or= 40 days) and after engraftment (41-180 days). Older patient age was associated with an increased risk during both periods. Chronic myelogenous leukemia (CML) in chronic phase was associated with low risk for early IA compared with other hematologic malignancies, aplastic anemia, and myelodysplastic syndrome. Multiple myeloma was associated with an increased risk for postengraftment IA. Use of human leukocyte antigen (HLA)-matched related (MR) peripheral blood stem cells conferred protection against early IA compared with use of MR bone marrow, but use of cord blood increased the risk of IA early after transplantation. Factors that increased risks for IA after engraftment included receipt of T cell-depleted or CD34-selected stem cell products, receipt of corticosteroids, neutropenia, lymphopenia, GVHD, CMV disease, and respiratory virus infections. Very late IA (> 6 months after transplantation) was associated with chronic GVHD and CMV disease. These results emphasize the postengraftment timing of IA; risk factor analyses verify previously recognized risk factors (GVHD, receipt of corticosteroids, and neutropenia) and uncover the roles of lymphopenia and viral infections in increasing the incidence of postengraftment IA in the 1990s.
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PMID:Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. 1239 25

To characterize the epidemiology and prognostic factors of invasive fusariosis in hematopoietic stem cell transplant (HSCT) recipients, the records of HSCT recipients from 9 hospitals (7 in Brazil and 2 in the United States) were retrospectively reviewed. Sixty-one cases were identified: 54 in allogeneic HSCT recipients and 7 in autologous HSCT recipients. The incidence of fusariosis among allogeneic HSCT recipients varied between a range of 4.21-5.0 cases per 1000 in human leukocyte antigen (HLA)--matched related transplant recipients to 20.19 cases per 1000 in HLA-mismatched transplant recipients. The median time period between transplantation and diagnosis of fusariosis was 48 days. Among allogeneic HSCT recipients, a trimodal distribution was observed: a first peak before engraftment, a second peak at a median of 62 days after transplantation, and a third peak >1 year after transplantation. The actuarial survival was 13% (median, 13 days). Persistent neutropenia was the single prognostic factor for death identified by multivariate analysis.
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PMID:Fusarium infection in hematopoietic stem cell transplant recipients. 1512 34

A 37-year-old Japanese man with systemic hemochromatosis due to multiple transfusions was referred to us for the treatment of severe aplastic anemia (SAA), from which he had been suffering for 24 years. The patient had diabetes arising from the hemochromatosis, chronic anal fissures, and a kidney abscess due to neutropenia. He was treated with a nonmyeloablative preconditioning regimen followed by non-T-cell-depleted (non-TCD) allogeneic peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical 2-loci-mismatched sibling. Prompt engraftment of granulocytes and platelets was observed, and graft-versus-host disease was easy to control. Noninherited maternal antigens in the donor were confirmed prior to PBSCT, and they were also detected in small quantities in the recipient. This report describes the first successful nonmyeloablative hematopoietic stem cell transplant in a heavily transfused SAA patient from an HLA-haploidentical 2-loci-mismatched sibling donor. The result suggests that a long-term fetomaternal microchimerism-positive sibling can be a second-line donor if an alternative HLA-identical donor is not available.
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PMID:Successful non-T-cell-depleted nonmyeloablative hematopoietic stem cell transplantation (NST) from an HLA-haploidentical 2-loci-mismatched sibling in a heavily transfused patient with severe aplastic anemia based on the fetomaternal microchimerism. 1517 Jan 64

Recombinant granulocyte colony-stimulating factor (r-GCSF) is used in autologous bone marrow/peripheral blood progenitor cell transplantation (ABMT/PBPC) to shorten the period of neutropenia. As these patients require platelet transfusions, their sera may be monitored for the presence of platelet/human leukocyte antigen (HLA) antibodies. Sera of some patients on r-GCSF (16 microg/kg/day) became difficult to evaluate in vitro for the presence of HLA and platelet antibodies because of apparently anomalous reactions in solid phase red cell adherence (SPRCA) assays. SPRCA tests were positive only when platelets were adhered to the polystyrene plates in the presence of glucose; when other simple sugars were used, the patients' sera failed to react. HLA Bw6-positive platelets were more likely than HLA Bw6-negative platelets to be reactive (p <.001). The transfusion of HLA Bw6-positive platelets to patients displaying this in vitro reactivity (positive patients) resulted in a 50 percent lower corrected count increment (CCI) than those given to patients without it (negative patients; p = <.001). When all transfusions were considered, the CCI for those of the positive patients was decreased 73 percent when compared to the control patients (p =.0005). The presence of the antibody also was associated with a twofold increase in the number of platelet transfusions given (p =.0005). ABMT/PBPC patients receiving r-GCSF may develop unexpected reactions on SPRCA antibody screens and poor responses to transfusion of Bw-6-positive platelets.
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PMID:Development of anti-Bw6 reactivity in patients receiving r-GCSF: a preliminary report. 1537 81

Allogeneic stem cell transplantation (SCT) using a myeloablative (MA) conditioning regimen is limited to relatively young patients because of increased transplant-related mortality in elderly patients. Nonmyeloablative (NMA) conditioning regimens have been developed aiming to reduce transplant mortality. In this study, we set out to evaluate the post-transplant occurrence of infectious complications in recipients of grafts from human leukocyte antigen (HLA)-identical sibling donors treated with either NMA or MA conditioning regimens. Data of 78 consecutively treated patients were analyzed. An NMA conditioning regimen was used in 40 patients and an MA regimen in 38 patients. A significantly lower rate of episodes of febrile neutropenia (0% vs. 34%, P<0.01) and post-transplant Epstein-Barr virus reactivations (0% vs. 18%, P<0.05) was found in SCT recipients treated with an NMA conditioning regimen compared with an MA conditioning regimen. Furthermore, fewer invasive fungal infections (2% vs. 12%, not significant) were diagnosed in the NMA group. The incidence of cytomegalovirus (CMV) reactivations and bacterial infections was low in both groups (CMV reactivations: 13% in both groups; bacterial infections: 10% in the NMA group vs. 8% in the MA group), while CMV disease developed in only 1 patient. Overall, compared to our MA regimen, we found a very low rate of infectious complications after NMA SCT.
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PMID:Low incidence of infectious complications after nonmyeloablative compared with myeloablative allogeneic stem cell transplantation. 1576 35

We describe the case of a 38-year-old male patient who had acute myeloid leukemia and developed prolonged neutropenia after induction chemotherapy. He developed thrombotic complications at multiple sites. Thrombophlebitis of the hemorrhoidal plexus became exacerbated and developed into critical cellulitis. Because the patient had no human leukocyte antigen-identical sibling, we considered an alternative donor. Because of the necessity for early neutrophil recovery to resolve the critical infection, we proceeded with allogeneic peripheral blood stem cell transplantation (PBSCT) from a microchimeric haploidentical sibling donor. We infused peripheral blood mononuclear cells directly into the patient without cryopreservation and thawing procedures. We aimed for the contaminating granulocytes to act as a granulocyte transfusion. Actually, the neutrophils increased to 1.6 x 10(9)/L on day 1, when the patient showed a temporary resolution of infection. Engraftment was achieved shortly after neutropenic nadir, and acute graft-versus-host disease (GVHD) has been well controlled. Although the patient experiences extensive chronic GVHD, he has been well as an outpatient with a 90% Karnofsky performance status score. The leukemia has been in complete remission for more than 1 year. These findings suggest the clinical utility of a salvage therapy with allogeneic PBSCT from a microchimeric haploidentical donor to treat refractory leukemia concurrent with life-threatening infection.
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PMID:Successful stem cell transplantation without cryopreservation from a microchimeric haploidentical sibling for refractory acute myeloid leukemia complicated with critical thrombophlebitis and cellulitis. 1726 7


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