Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.
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PMID:Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure. 214 25

Data were obtained from 46 patients with severe aplastic anemia (SAA) who received bone marrow transplants (BMT) from donors other than genotypically HLA-identical siblings. The data were collected in the SAA Registry of the European Bone Marrow Transplant Group. The donors were non-HLA-identical siblings in six cases, parents in 28 cases, a son in one case and unrelated individuals in 11 cases. Fifteen donor-recipient pairs were HLA-A, -B and -DR identical and mutually non-reactive in mixed lymphocyte culture; nine were mismatched at one locus, 17 were mismatched at two or more loci and in five cases data were not available for D/DR determinants. Actuarial survival was predicted by the degree of mismatch. It was 45% for phenotypically HLA-identical grafts, 25% for grafts mismatched at one locus and 11% for graft mismatched at more than one locus. Whether the graft was derived from a family member or an unrelated donor seemed to be less important and results were comparable. Age, patient sex and year of transplant had no significant influence on survival. The use of cyclosporine (CSA) for graft-versus-host disease (GVHD) prophylaxis (n = 21, survival 34%) appeared superior to both methotrexate (n = 9, survival 11%) and to CSA with T cell depletion of donor marrow (n = 13, survival 14%). The causes of death were rejection (n = 15), GVHD (n = 13), pneumonitis (n = 5) and infection (n = 1). Twelve patients are alive at 16-84 months post-BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for severe aplastic anemia from donors other than HLA identical siblings: a report of the BMT Working Party. 306 21

Gold salt therapy-induced pneumonitis is a rare complication in patients with rheumatoid arthritis (RA). We studied HLA-A, B, C, D/DR, and complement factor B (Bf) and C4 alleles in 17 patients with RA and gold-induced pneumonitis and found that these patients had strikingly homogeneous major histocompatibility complex (MHC) markers. Eight of them (47 percent) had the alleles HLA-A3 B35 Dwl BfF C4A3,2 (BO), which were shown by family studies of some patients to be inherited as an extended MHC-haplotype with an apparent gene duplication in the C4A locus. The other high-risk phenotype, HLA-B40 with a C4 null allele, was found in eight patients (47 percent). All but three of the 17 patients had at least one of the two high-risk markers, the frequency of these combinations being clearly higher than in the two control groups: patients with RA but with no gold-induced side effects and healthy individuals. Our study shows that use of several MHC markers together results in a strong association between the markers and the disease.
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PMID:Patients with rheumatoid arthritis and gold-induced pneumonitis express two high-risk major histocompatibility complex patterns. 311 96

Obliterative bronchiolitis (OB) after lung transplantation is the end result of multiple immunologic, virologic, genetic, and environmental effects on the transplanted lung. In this study, we first analyzed risk factors for OB in a single-center population of 152 lung transplant recipients. We then examined the influence of donor and recipient HLA mismatching on progression to OB, and on the identified risk factors for OB. The median time to onset of OB for the entire study population was 2.7 yr. The significant risk factors for OB by multivariate analyses were grade A2 or A3 acute rejection (p = 0.0126) and cytomegalovirus (CMV) pneumonitis (p = 0.0358). The only significant HLA risk factor for OB was mismatching at the HLA-A locus (p = 0.0144). On the basis of Cox proportional hazards modeling, a predictive formula was derived to estimate the risk of OB after lung transplantation. Although mismatching at the HLA-DR locus was a significant risk factor for CMV pneumonitis in recipients exposed to CMV before transplantation (p = 0.0199), and protected against acute rejection, it did not independently protect against OB. These results indicate that HLA mismatches between donors and recipients significantly influence the development of OB both directly, and indirectly, by influencing the major risk factors for OB.
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PMID:Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation. 1117 19

We here report 25 patients with nonmalignant disorders, ie, severe aplastic anemia (SAA, n = 12) or inborn errors of metabolism (IEM, n = 13), who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated high-resolution typed HLA-A, -B, and -DRbeta1 identical donors. One patient had an HLA-B subtype-mismatched donor. Conditioning for SAA mainly consisted of cyclophosphamide and total body irradiation, and that for IEM consisted of busulfan and cyclophosphamide. All patients received antithymocyte globulin during conditioning. After HSCT, they were given cyclosporine combined with methotrexate for immunosuppression. Two patients rejected their grafts: 1 died of pneumonia, and the other was successfully regrafted. The cumulative incidence of acute graft-versus-host disease grades II to IV was 24%, whereas chronic graft-versus-host disease occurred in 21%. The 5-year survival rates were 83% in the SAA group and 85% in those with IEM. We conclude that HSCT with HLA-A, -B, and -DRbeta1 genomically matched unrelated donors in combination with antithymocyte globulin in the conditioning regimen gives encouraging results in patients with SAA or IEM.
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PMID:Allogenic stem cell transplantation for nonmalignant disorders using matched unrelated donors. 1557 Feb 56

Pulmonary complications after allogeneic hematopoietic stem-cell transplantation (HSCT) remain 1 of the most important causes of morbidity and mortality. This study evaluates the change over time of incidence, aetiology and risk factors for death related to pneumonia within 3 months after HSCT. 997 patients who underwent HSCT were studied retrospectively. Most patients (83%) had a haematological malignancy. The majority (89%) had an HLA-A, -B, and -DR matched related or unrelated donor. Conditioning consisted of cyclophosphamide and total-body irradiation or busulfan and graft-versus-host disease prophylaxis of cyclosporin and methotrexate in most cases. Death related to pneumonia occurred in 56 (5.6%) patients. Cytomegalovirus (37%) was the main pathogen involved, especially during the first 2 decades studied. In the multivariate risk factor analysis, we found that death from pneumonia was significantly associated with receiving a T-cell depleted graft (p<0.001), bacteraemia (p=0.001), and y of transplantation (p<0.001). In patients receiving a transplant during the last decade, the incidence of death related to pneumonia was 2.8% compared to 8.9% during the first decade. We conclude that the rate of mortality related to pneumonia has decreased over time, possibly as a result of improved diagnostic, prophylactic and therapeutic methods and treatment.
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PMID:Decreasing mortality rate in early pneumonia following hematopoietic stem cell transplantation. 1714 63