Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A forty-year-old man underwent an allogeneic BMT from his HLA identical sister. GvHD prophylaxis was done with cyclosporine (CyA), methotrexate and prednisone (PDN). On day +90 extensive GvHD was noted and higher doses of immunosuppressive drugs alternating CyA with PDN were initiated. Patient's follow-up was complicated by intermittent episodes of leukopenia and monthly episodes of sinusitis or pneumonia. One year after BMT, the patient developed hoarseness and nasal voice. No etiologic agent could be identified on a biopsy sample of the vocal chord. Upon tapering the doses of immunosuppressive drugs, the patient had worsening of chronic GvHD and was reintroduced on high doses of cyclosporine alternating with prednisone on day +550. Three months later, GvHD remained out of control and the patient was started on azathioprine. On day +700, hoarseness and nasal voice recurred. Another biopsy of the left vocal chord failed to demonstrate infection. Episodes of sinusitis became more frequent and azathioprine was withheld 3 months after it was started. One month later, the patient had bloody nasal discharge and surgical drainage of maxillary sinuses was performed. Histopathology showed hyphae and cultures grew Scedosporium apiospermum. Itraconazole 800 mg/day was initiated. The patient developed progressive respiratory failure and died 15 days later.
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PMID:Scedosporium apiospermum sinusitis after bone marrow transplantation: report of a case. 1003 78

Although progress has been made in the diagnosis and management of respiratory complications after BMT, such complications are still frequent and are a major cause of morbidity and mortality. The use of CMV-negative marrow and blood products, surveillance bronchoscopies, and prophylactic use of antivirals have significantly reduced the incidence of CMV pneumonia. DNA amplification techniques have allowed earlier detection of viral respiratory infections, and early detection of localized invasive aspergillosis can improve survival with lung resection and antifungal therapy. Finally, consideration for open lung biopsy should include the patient's degree of preoperative respiratory impairment, because this may relate to early postoperative survival.
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PMID:Thoracic complications related to bone marrow transplantation. 1007 85

Interleukin 10 (IL-10) is a potent inhibitor of proliferative T cell responses toward alloantigens, and suppresses the production of pro-inflammatory cytokines which are important in cellular activation and recruitment to sites of inflammation. Because of these properties, we hypothesized that high IL-10 production in patients prior to BMT may predict a better outcome. To investigate this, peripheral blood mononuclear cells (PBMNC) were obtained from 58 recipients (11 autologous, 25 related donor (RD), and 22 unrelated donor (URD)), prior to conditioning therapy. PBMNC were cultured for 24 h in the presence and absence of lipopolysaccharide (LPS) and culture supernatants were assayed for IL-10 using an ELISA method. Spontaneously produced and LPS-stimulated IL-10 levels were correlated with the development of transplant-related complications (TRC) including grade II-IV acute GVHD, veno-occlusive disease, idiopathic pneumonia syndrome and multi-organ dysfunction syndrome, and with death before day 100. For the autologous group, there were no TRC and only one death prior to day 100; therefore, no statistical comparisons to IL-10 levels could be made. In the RD group, 36% developed one or more TRC and 24% died before day 100; however, there were no statistically significant associations between spontaneous or LPS-induced IL-10 levels. In URD patients 41% developed TRC and 55% died prior to day 100. In this group, higher levels of spontaneous IL-10 production were associated with a lower overall occurrence of TRC (P = 0.03) and early death (P = 0.04). Our data would indicate that higher levels of IL-10 production prior to URD BMT may predict fewer TRC, as well as early deaths. The hypothesis that high IL-10 production prior to BMT may decrease complications following URD BMT warrants further testing.
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PMID:High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths. 1038 51

A 13-year-old splenectomized, multitransfused beta-thalassemia major, male patient received an allogenic BMT from his HLA-compatible brother after suffering grade III regimen-related pulmonary toxicity. He developed features of CMV pneumonitis with positive pp65 CMV antigenemia involving 2.5% peripheral blood neutrophils from day +46. The patient received intravenous immunoglobulin and ganciclovir 5 mg/kg intravenously twice daily. His neutrophil count was maintained above 1 x 10(9)/l by G-CSF 5 microg/kg subcutaneously as and when required. From day 7 onwards following twice daily ganciclovir his peripheral blood smear started showing isolated cytoplasmic inclusions, 1-3 per neutrophil, 3-5 mu in diameter, involving 2-3% of the neutrophils and occasional monocytes. Transmission election microscopy of peripheral blood neutrophils showed type I and type II intranuclear inclusions. These inclusions disappeared within 48 h of stopping ganciclovir. Inclusions were not seen in three patients who were given prophylactic ganciclovir 5 mg/kg once daily for 5 days every week following allogenic BMT after the same conditioning regimen. These patients were also negative for CMV antigenemia. Development of type I and type II intranuclear inclusions in blood neutrophils in patients receiving ganciclovir therapy has not been reported previously, and the striking light microscopic changes provide simple morphological evidence of the toxic effect of this drug on blood neutrophils.
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PMID:Ultrastructural changes in peripheral blood neutrophils in a patient receiving ganciclovir for CMV pneumonitis following allogenic bone marrow transplantation. 1046 35

Respiratory syncytial virus (RSV) pneumonia in BMT recipients carries a mortality rate of approximately 50-70% despite ribavirin (Virazole) treatment. In both immunocompetent and immunocompromised animal models, RSV neutralizing antibodies rapidly reduce pulmonary virus load after a single dose. RSV-IGIV (RespiGam) is an IgG immune globulin with high concentrations of RSV neutralizing antibody (>19 200 MU/ml). From June 1991 to February 1996, a compassionate-use protocol using RSV-IGIV for treatment of RSV infections was conducted. Eleven children at multiple centers, mean age 3.3 years (4 months to 9 years), were undergoing BMT and met the protocol criteria. They received a single 1500 mg/kg dose of RSV-IGIV infused over 12 h at a median of 5 days (1-37 days) after RSV symptom onset. Ten of these patients received prior or concurrent aerosolized ribavirin. Serum RSV neutralizing titers were measured in five patients and showed a 3- to 30-fold increase 24 h after RSV-IGIV infusion. Adverse events were mild. One of 11 (9.1%) patients died from their RSV illness (91% RSV survival). In comparison to previously published reports, RSV-IGIV treatment of RSV pneumonia in BMT patients may increase survival above that in such patients treated with ribavirin alone. Bone Marrow Transplantation (2000) 25, 161-165.
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PMID:Respiratory syncytial virus immune globulin treatment of lower respiratory tract infection in pediatric patients undergoing bone marrow transplantation - a compassionate use experience. 1067 74

We investigated keratinocyte growth factor (KGF) as a pretreatment therapy for idiopathic pneumonia syndrome (IPS) generated as a result of lung damage and allogeneic T cell-dependent inflammatory events occurring in the early peri-bone marrow (BM) transplant (BMT) period. B10.BR (H2(k)) recipient mice were transplanted with C57BL/6 (H2(b)) BM with spleen cells after lethal irradiation with and without cyclophosphamide conditioning with and without subcutaneous KGF pretreatment. KGF-pretreated mice had fewer injured alveolar type II (ATII) cells at the time of BMT and exhibited ATII cell hyperplasia at day 3 post-BMT. The composition of infiltrating cells on day 7 post-BMT was not altered by KGF pretreatment, but the frequencies of cells expressing the T-cell costimulatory molecules B7.1 and B7.2 and mRNA for the cytolysin granzyme B (usually increased in IPS) were decreased by KGF. Sera from KGF-treated mice had increases in the Th2 cytokines interleukin (IL)-4, IL-6, and IL-13 4 days after cessation of KGF administration (i.e., at the time of BMT). These data suggest that KGF hinders IPS by two modes: 1) stimulation of alveolar epithelialization and 2) attenuation of immune-mediated injury as a consequence of failure to upregulate cytolytic molecules and B7 ligand expression and the induction of anti-inflammatory Th2 cytokines in situ.
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PMID:KGF pretreatment decreases B7 and granzyme B expression and hastens repair in lungs of mice after allogeneic BMT. 1078 30

Cunninghamella spp., in the class Zygomycete and order Mucorales, are unusual opportunistic pathogens that have been identified with increased frequency in immunocompromised patients. Infections with this group of organisms have been seen most frequently in patients with hematologic malignancy. We describe an allogeneic bone marrow recipient who developed fungal pneumonitis and disseminated fungal dermatitis caused by Cunninghamella spp. To our knowledge, this is the first reported case of Cunninghamella infection in a BMT recipient. The case highlights the mortality associated with opportunistic infections in immunocompromised patients and confirms the risk factors associated with non-candida fungal infections after bone marrow transplantation.
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PMID:Cunninghamella infection post bone marrow transplant: case report and review of the literature. 1084 36

We describe two patients who developed respiratory syncytial virus (RSV) pneumonia after BMT. One died of RSV pneumonia after three courses of steroid pulse therapy. Surprisingly, RSV antigen was identified in the bronchoalveolar lavage fluid (BALF) obtained post mortem. Steroid pulse therapy might have suppressed anti-RSV immunity, leading to persistent RSV infection for more than 1 month. The other patient received donor lymphocyte infusions (DLI) for relapsed plasma cell leukemia, while having active RSV pneumonia. His respiratory condition improved after DLI, and RSV antigen disappeared in BALF and nasal swabs. DLI might be effective in cases of life-threatening RSV pneumonia.
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PMID:Donor lymphocyte infusion for treatment of life-threatening respiratory syncytial virus infection following bone marrow transplantation. 1101 50

Respiratory viral infections are major causes of morbidity and mortality in children with SCID and other primary immunodeficiencies who require BMT. Twenty-two of 73 (30%) such children were admitted with respiratory viral infections, of whom 13/22 (59%) died. All viruses were detected in nasopharyngeal aspirate (NPA). Virus was only found in BAL in those with LRTI. Eleven of 22 (50%) had paramyxovirus infections, all with severe viral pneumonitis which worsened post BMT. Five of 11 (45.5%) survived overall. All 11 received aerosolised ribavirin; five of 11 received additional inhaled immunoglobulin and corticosteroid. Three of 5 (60%) survived compared with two of six (33.3%) not thus treated. Three of 22 (13.6%) had adenoviruses; one died of disseminated disease, including pneumonia despite intravenous ribavirin. Eleven patients had rhinovirus detected; nine of 11 (82%) were asymptomatic or coryzal and survived. Two patients with additional severe lung pathologies had LRT rhinovirus and died. All patients received intravenous immunoglobulin. No treatments resulted in viral clearance without successful T cell engraftment. Respiratory viruses, particularly paramyxoviruses and adenoviruses are common, significant pathogens in these patients, significantly worsening outcome of BMT. NPA is an ideal specimen for diagnosis and monitoring of infection. Aggressive treatments may reduce viral replication and damage. Nebulised immunoglobulin and corticosteroid in LRTI may improve respiratory function and outcome.
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PMID:Respiratory viral infections in primary immune deficiencies: significance and relevance to clinical outcome in a single BMT unit. 1110 9

We have previously shown an association between growth factor-induced upregulation of surfactant protein (SP)-A and suppression of alveolar inflammation in our murine model of donor T cell-dependent lung dysfunction after bone-marrow transplantation, referred to as idiopathic pneumonia syndrome (IPS). We hypothesized that SP-A protects the lung in vivo from IPS injury by downregulation of alveolar inflammation. Human SP-A (100 microg), purified by n-butanol extraction or preparative isoelectric focusing, was transtracheally instilled on Day 4 after BMT during a time of in vivo donor T-cell activation. At 48 h after treatment, immunohistochemical staining of lung sections showed that SP-A did not alter T cell- dependent cellular infiltration. However, macrophages from SP-A-instilled mice were less injured and spontaneously produced less tumor necrosis factor-alpha than did cells from buffer-instilled mice. Although exogenous SP-A did not significantly alter bronchoalveolar lavage fluid (BALF) high levels of total protein (TP), an inverse correlation between BALF SP-A and TP concentrations (r = -0.65; P = 0.02) was observed in SP-A-treated but not in buffer-instilled mice. The only difference between the effects of the two sources of SP-A was that butanol-extracted SP-A, but not isoelectric focusing-purified SP-A, suppressed the interferon-gamma/nitric oxide pathway. We conclude that SP-A downregulates T cell-dependent alveolar inflammation by multiple pathways leading to decreased IPS injury.
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PMID:Human surfactant protein a suppresses T cell-dependent inflammation and attenuates the manifestations of idiopathic pneumonia syndrome in mice. 1135 Aug 21


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