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 here a 6-month-old boy with severe congenital neutropenia (SCN) successfully treated by cord blood stem cell transplantation (CBSCT) from an unrelated donor. He had recurrent life-threatening respiratory infection due to severe neutropenia that was refractory to recombinant human granulocyte colony-stimulating factor (rhG-CSF). Because he had no HLA-matched sibling and no time to wait for unrelated donor, he received HLA-matched unrelated CBSCT as determined by DNA typing. A total of 6.4 x 10(7) CB nucleated cells/kg was infused after conditioning with busulfan/horse antihuman thymocyte serum/cyclophosphamide. No GVHD developed under the treatment with cyclosporin A and methyl prednisolone. The neutrophil count reached 0.5 x 10(9)/l on day 14, reticulocyte 1% on day 13 and platelet count over 50 x 10(9)/l on day 31. We conclude that unrelated CBSCT can be an indication for some cases of SCN, who have recurrent life-threatening infections and are refractory to rhG-CSF, and have no HLA-matched sibling.
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PMID:Umbilical cord blood stem cell transplantation from unrelated HLA-matched donor in an infant with severe congenital neutropenia. 1500 40

In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy (BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2 Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity. In a pilot protocol we treated 10 patients, 22-62 (median 47) years of age with high-risk or refractory Hodgkin's or non-Hodgkin's lymphoma. Donors were HLA identical siblings (eight) or unrelated volunteers. None died during the neutropenic phase after BEAM which lasted up to the RIC HSCT. The duration of neutropenia was 31-43 (median 36) days. All patients engrafted and nine achieved CR. All developed acute GvHD (median grade III) and all patients at risk developed chronic GvHD. Three patients died of GvHD. One relapsed and six patients are in continuous CR 10-32 (median 15) months after HSCT. This approach appears feasible and results in a high response rate. Neutropenia duration is of concern. It remains to be tested whether separation of debulking chemotherapy and induction of allogeneic effects confers an advantage.
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PMID:High-dose chemotherapy using BEAM for tumor debulking without stem cell support followed by early allogeneic reduced intensity conditioning transplantation to induce a graft-versus-lymphoma effect in patients with high risk or refractory lymphoma. 1506 93

The GLAM assay, a combined flow cytometric immunofluorescence test that simultaneously detects antibodies to granulocytes, lymphocytes, and monocytes, was used in the investigation of autoimmune neutropenia. This method avoids the need for a succession of immunofluorescence tests, first against granulocytes and then against lymphocytes, in order to distinguish granulocyte-specific from granulocyte/lymphocyte-reactive antibodies, such as noncomplement- fixing anti-HLA sera. Samples from 18 patients with a suspected diagnosis of autoimmune neutropenia were referred for investigation. Leukocytes were harvested in sufficient quantities from 10 of the patients such that neutrophil and lymphocyte direct antiglobulin tests (DATs) and antibody screening and identification could be undertaken (in one case the results were inconclusive). Only three of these 10 patients had DAT-positive granulocytes, and one of these three also had DAT-positive lymphocytes. One further patient demonstrated DAT-positive lymphocytes in the absence of granulocyte-bound IgG, despite a presumed diagnosis of autoimmune neutropenia, rather than pancytopenia. This was the only patient in this cohort who had demonstrable leukocyte antibodies reacting with lymphocytes but not granulocytes. Of the remaining eight patients (not evaluable for granulocyte or lymphocyte DATs), five had free leukocyte antibodies in the serum; three of these five had both granulocyte- and lymphocyte-reactive antibodies free in the serum and two only had granulocyte-specific antibodies.
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PMID:The GLAM test: a flow cytometric assay for the detection of leukocyte antibodies in autoimmune neutropenia. 1538 29

Felty's syndrome (FS) comprises a triad of rheumatoid arthritis (RA), neutropenia and splenomegaly, occurring in less than 1% of RA patients. Clinically it is characterized by severe joint destruction contrasting with moderate or absent joint inflammation and severe extra-articular disease, including a high frequency of rheumatoid nodules, lymphadenopathy, hepatopathy, vasculitis, leg ulcers, skin pigmentation etc. Recurrent bacterial infections are mostly due to the severe, otherwise unexplained neutropenia. The cause of neutropenia lies in both decreased granulopoiesis and increased peripheral destruction of granulocytes. Recurrent infections may lead to increased mortality. Spontaneous remission of the syndrome also occurs. Over 95% of FS patients are positive for rheumatoid factor (RF), 47-100% are positive for antinuclear antibody (ANA), and 78% of patients have the HLA-DR4*0401 antigen. Some 30% of FS patients have large granular lymphocyte (LGL) expansion. LGL expansion associated with uncomplicated RA is immunogenetically and phenotypically very similar to but clinically different from FS. Neutropenia of FS can be effectively treated with disease-modifying anti-rheumatic drugs (DMARDs), the widest experience being with methotrexate (MTX). Results of treatment with granulocyte colony-stimulating factor (G-CSF) are encouraging, but there is no experience with other biological agents. Splenectomy results in immediate improvement of neutropenia in 80% of the patients, but the rate of infection decreases to a lesser degree.
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PMID:Felty's syndrome. 1545 23

Severe chronic neutropenia (SCN) is characterized by severe recurrent bacterial infections during infancy. Blood or marrow transplantation (BMT) is the only curative option for patients with refractory disease. This report describes the case of a 4-year-old girl with refractory SCN, who received a bone marrow transplant from a highly matched donor after becoming HLA sensitized to multiple granulocyte transfusions. She is clinically well with normal blood counts and stable mixed chimerism 3 years after BMT. She experienced no graft rejection or graft versus host disease.
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PMID:Successful engraftment following unrelated donor transplant in an alloimmunized patient with Kostmann syndrome. 1548 Oct 82

Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe congenital neutropenia (SCN). Among 101 cases of SCN included in the French Severe Chronic Neutropenia Registry, nine patients received HSCT between 1993 and 2003, in seven institutions. The indications were nonresponse to G-CSF therapy in four cases, bone marrow failure in one case, and myelodysplastic syndrome or leukemia in four cases. The conditioning regimen consisted of total body irradiation in two cases and chemotherapy alone in the other seven cases. Seven patients received stem cells from unrelated donors and two from identical siblings. Engraftment occurred in all but one of the patients. Three patients died. The respective causes of death were graft-versus-host disease, infection, and EBV post-transplant lymphoproliferative disease. Six patients are alive and in complete remission, with a median follow-up of 3.1 years. These results indicate that HSCT is feasible for patients with SCN who do not respond to G-CSF, who have malignant transformation, or who are at a high risk of malignant transformation, even if an HLA-identical sibling donor is not available.
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PMID:Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register. 1548 67

Patients with sickle cell disease (N = 3) and thalassemia (N = 1) with high-risk features received hematopoietic stem cell transplantations (HCT) to induce stable (full or partial) donor engraftment. Patients were 9-30 years of age. Fludarabine, rabbit anti-thymocyte globulin (ATG), and 200 cGy total body irradiation were administered pre-transplant. Patients received bone marrow (N = 3) or peripheral blood stem cells (N = 1) from HLA-identical siblings, followed by mycophenolate mofetil and cyclosporine for post-grafting immunosuppression. Significant lymphopenia, but only moderate neutropenia and thrombocytopenia developed post transplant. No grade IV nonhematological toxicities or acute graft-versus-host disease (GVHD) were observed. At 3 months after transplantation, three of four patients had evidence of donor myeloid chimerism (range, 15-100%). However, after post transplant immunosuppression was discontinued, graft rejection occurred in all but one patient. This patient is now doing well 27 months post transplant with full donor engraftment. One patient died after a second transplant, and another patient experienced a stroke as her graft was being rejected. These results suggest that stable donor engraftment after nonmyeloablative HCT is difficult to achieve among immunocompetent patients with hemoglobinopathies and that new approaches will need to be developed before wider application of this transplantation method for hemoglobinopathies.
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PMID:Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. 1553 1

Between November 1998 and October 1999 authors treated five multiple myeloma patients with an allogeneic peripheral blood stem cell transplantation from HLA-identical sibling using a non-myeloablative conditioning regimen. The median age at the time of transplantation was 58 (range: 47-65) years. In all patients one (n = 3) or two (n = 2) autologous peripheral blood stem cell transplantations were already performed. Conditioning was performed with fludarabine, oral busulfan and anti-T-lymphocyte globulin. All patients engrafted from 13 to 18 (median: 17) days from transplantation. The duration of neutropenia (absolute neutrophiles count < 500/microl) and thrombocytopenia (platelets < 20,000/microl) ranged between 4 and 19 (median: 18) and between 13 and 18 (median: 17) days, respectively. In the period of posttransplant pancytopenia two patients developed mild gastrointestinal mucositis and two pulmonary complications (bronchopneumonia and dyspnoe of unknown etiology). Two patients had grade III-IV acute graft-versus-host disease (GvHD), none had extensive chronic GvHD. Two patients received prophylactic donor-lymphocytes infusions 200 and 225 days from transplantation. One of them developed grade III acute GvHD. All patients responded. One achieved complete and four partial remission of the disease. One patient died 111 days from transplantation due to bronchopneumonia, four are alive and well, in the stable disease, 35, 36, 51 and 52 weeks after transplantation. It can be concluded that allogenic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen is an effective way of the multiple myeloma treatment with an acceptable toxicity.
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PMID:[The treatment of multiple myeloma with an allogeneic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen]. 1563 96

The incidence of alloimmune neonatal neutropenia combined with neonatal alloimmune thrombocytopenia is very low. We report a case of a neonate who suffered severe neutropenia and thombocytopenia with widespread petechial spots. The presence of alloantibodies in mother's and patient's sera was analyzed by lymphocytotoxicity test, agglutination test, granulocyte indirect immunofluorescence test, platelet immunofluorescence test (PIFT) and solid phase enzyme-linked immunosorbent assay. Human neutrophil antigens (HNA) and human platelet antigen (HPA) genotypes were tested by polymerase chain reaction analyses. The mother's and patient's sera reacted with neutrophils and lymphocytes of the father. PIFT revealed the presence of IgG anti-platelet antibodies in the patient's serum but the test was negative in the maternal serum. Analyses of HNA-1 and HPA genotypes of the family revealed maternal-neonatal HNA-1a and HPA-3b mismatch. The study of the mother's and patient's sera showed the presence of anti HNA1a, HPA-3b and HLA antibodies specific for HLA-A3 and HLA-B38 antigens. These results suggest that the transplacental passage of maternal HNA-1a, HPA-3b and HLA alloantibodies caused neutropenia and thrombocytopenia in this patient.
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PMID:Alloimmune neonatal neutropenia and thrombocytopenia associated with maternal anti HNA-1a, HPA-3b and HLA antibodies. 1585 61

Agranulocytosis is a disorder characterized by a severe decrease in the number of granulocytes in blood, that frequently occurs as an adverse reaction to some drugs. By now, there are no reports in literature of agranulocytosis caused by tumur necrosis factor-alpha blockers. We describe the case of a 20-year-old Caucasian male affected by enteropathic (Crohn's disease) spondyloarthropathy HLA B27 negative, successfully treated with infliximab. After the second infliximab infusion, he was found to have a severe transient neutropenia (0.5 x 10(9)/L). Routine serum chemistry and full blood cell count (apart from neutrophil count) were normal. Serology excluded an active infection. Bone marrow needle aspirate showed a normal trilineage differentiation. Autoantibody assessment showed negative ANA, anti-dsDNA, anti-ENA, and ANCA, but positive granulocyte-bound antibodies (GBA) and neutrophil-specific (CD 16+)-bound antibodies (anti-NA). Ten weeks after infliximab infusion, neutrophil count and GBA and anti-NA assay returned spontaneously within normal range and we observed the same progress after every successive infliximab infusion we performed. These data indicated that infliximab possibly triggered production of granulocyte and neutrophil autoantibodies with resultant autoimmune agranulocytosis.
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PMID:Drug-induced agranulocytosis during treatment with infliximab in enteropathic spondyloarthropathy. 1589 99


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