Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of 1506 marrow transplant patients from 1980 through 1986 reviewed for risk factors for invasive candidal infection defined by positive blood cultures, biopsy, or histologic evidence of tissue invasion, 171 (11.4%) had invasive infection, with a significantly higher incidence in the more recent years of review; 40% (69 patients) had evidence of tissue-invasive disease without fungemia. Of 102 patients with fungemia, 45% had candidemia alone with a mortality of 39%. Mortality in patients with tissue involvement was 90% with or without fungemia. Factors that increased infection were age, acute graft-versus-host disease, and donor mismatch. Factors that decreased infection included conditioning with 12 Gy of fractionated irradiation and cyclophosphamide, transplantation for aplastic anemia, and more rapid engraftment. Among fungemic patients, the number of days of fungemia was a risk factor for tissue invasion while more rapid engraftment was protective.
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PMID:Clinical features and analysis of risk factors for invasive candidal infection after marrow transplantation. 189 35

Despite the use of conventional chemoprophylaxis regimens, patients receiving unrelated-donor BMT are at high risk of developing severe acute GVHD. We evaluated a prophylactic regimen combining CsA, MTX and anti-CD5-ricin A chain immunotoxin (H65-RTA) in 31 patients; pentoxifylline was also given to reduce the anticipated nephrotoxicity of CsA. In most cases, planned doses of CsA, MTX and H65-RTA were given (i.e. to 77%, 77% and 93% of patients, respectively). Although fluid retention requiring diuretic therapy was frequent, only 1 patient had a > 10% unexplained increase in body weight during the first 21 days post-BMT. Also, while significant increase of the baseline serum creatinine was noted in 7 patients, none required dialysis. One patient suffered a reversible allergic reaction to the immunotoxin; no other side effects attributable to this regimen were observed. All but 2 patients engrafted (1 died of fungemia on d + 19 and the other had persistent leukemia) and no late graft failures were observed. Seventeen patients developed acute GVHD grade > or = II (probability, 58% [95% CI 41-76%]); 7 had grade > or = III (probability, 24% [95% CI 12-43%]). In the 27 patients who achieved stable engraftment and have survived beyond d + 100, the 3-year probability of developing chronic GVHD was 66% (95% CI 48-84%). As of the last follow-up prior to 01 May 1994, 13 patients are alive in CR and one in relapse; 9 of these patients are off all immunosuppressives and well. Four other patients relapsed and died, and 13 died of other transplant-related causes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantation. 753 67

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.
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PMID:Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention. 804 48

Allogeneic BMT is the treatment of choice for patients with SAA who have an HLA-identical sibling donor. The results, however, have been relatively poor for transplants from partially matched family donors or unrelated donors because of the high incidence of graft rejection and/or GVHD. Six multiply transfused patients received a novel conditioning regimen of CY 200 mg/kg and TBI 800 cGy prior to receiving marrow from their HLA-haploidentical family donors. Three recipient-donor pairs were mismatched for one HLA locus, one for two loci and two for three loci. A combination of MTX and CsA was used for GVHD prophylaxis. Engraftment was noted in all six patients. Acute GVHD occurred in four patients, two each for grade I and II, respectively. One patient, who was ABO-compatible with her donor had delayed onset of pure red cell aplasia (PRCA) which completely recovered 6 months after additional immunotherapy with prednisolone. There were two deaths; both occurred while patients were on treatment for GVHD. One was from systemic fungemia and the other probably from cytomegalovirus interstitial pneumonitis (CMV-IP). Four patients (66.7%) have been alive and disease-free for more than 8.2, 27.3, 38.4 and 47.2 months after BMT, respectively. The results suggest that CY/TBI-800 may be a simple and effective conditioning regimen for SAA patients receiving BMT from family members other than HLA-identical siblings.
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PMID:CY/TBI-800 as a pretransplant regimen for allogeneic bone marrow transplantation for severe aplastic anemia using HLA-haploidentical family donors. 886 34

Graft-versus-host disease in solid organ transplantation is very rare, but the prognosis is poor when the condition causes pancytopenia. We report a case of graft-versus-host disease in a heart-lung transplant recipient who at 2 weeks after transplantation had development of features of graft-versus-host disease, including bone marrow aplasia, that could not be attributed to drugs or viral infections. The diagnosis was confirmed by skin biopsy and demonstration of chimerism of peripheral lymphocytes. Augmentation of immunosuppression with intravenous methylprednisolone resulted in improvement in liver function but had no effect on the pancytopenia. Mediastinal irradiation was given with increase in both white blood cell and platelet counts. Unfortunately the patient eventually died of gastrointestinal bleeding and fungemia.
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PMID:Mediastinal irradiation for graft-versus-host disease in a heart-lung transplant recipient. 932 50

Experimental data have implicated intravenous lipids as being immunosuppressive, yet evidence that lipids are associated with an increase in clinically documented infections is sparse. A prospective trial conducted in patients with hematologic malignancies who were undergoing bone marrow transplantation compared the incidence of bacteremia and fungemia during the first month after the transplant. Patients (n = 512) were randomly assigned to receive 6-8% (low dose) or 25-30% (standard dose) of total daily energy as a 20% lipid emulsion. An adaptive randomization scheme stratified for treatments that might influence infection outcome (hematopoietic growth factors, fluconazole, graft-versus-host disease prophylaxis with steroids, pentoxifylline, intravenous immunoglobulin, and total body irradiation). The transplant type (autologous, related family donor, or unrelated donor) did not differ in distribution between treatment groups. Of the evaluable patients (n = 482), 55 patients in the standard-dose lipid group developed bacteremia or fungemia compared with 54 in the low-dose lipid group. The log-rank test comparing the time to first infection found no association between the incidence of bacteremia or fungemia and intravenous lipid (P = 0.95). Similar results were found when analyzed as intent-to-treat (P = 0.98), when bacterial or fungal infections at all sites were included (P = 0.94), and when the observation period was extended to 60 d (P = 0.58 for blood infections, P = 0.77 for infections at all sites). These data indicate that moderate amounts of intravenous lipid rich in linoleic acid are not associated with an increased incidence of bacterial or fungal infections in patients undergoing bone marrow transplantation and receiving total parenteral nutrition.
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PMID:Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation. 958 51

Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.
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PMID:Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. 1178 48

Fusarium species frequently implicated in human infections include F. solani, F. oxysporum and F. moniliforme. Among immunocompetent patients, tissue breakdown (as caused by trauma, severe burns or foreign body) is the risk factor for fusariosis. Infections include keratitis, onychomycosis and occasionally peritonitis and cellulitis. Treatment is usually successful and requires removal of the foreign body as well as antifungal therapy. Among immunocompromised patients, mainly patients with haematological malignancies, Fusarium spp. are the second most common pathogenic mould. Risk factors for disseminated fusariosis include severe immunosuppression (neutropenia, lymphopenia, graft-versus-host disease, corticosteroids), colonisation, tissue damage, and receipt of a graft from an HLA-mismatched or unrelated donor. Clinical presentation includes refractory fever (> 90%), skin lesions and sino-pulmonary infections ( approximately 75%). Type of skin lesions includes ecthyma-like, target, and multiple subcutaneous nodules. Skin lesions lead to diagnosis in > 50% of patients and precede fungemia by approximately 5 days. In contrast to disseminated aspergillosis, disseminated fusariosis can be diagnosed by blood cultures in 40% of patients. Histopathology reveals hyaline acute-branching septate hyphae similar to those found in aspergillosis. Mortality from fusarial infections in immunocompromised patients ranges from 50% to 80%. Host immune status is the single most important factor predicting outcome. Persistent neutropenia and corticosteroid therapy significantly affect survival. Optimal treatment has not been established. Anecdotal successes have been reported with various agents (high-dose amphotericin B, lipid-based amphotericin B formulations, itraconazole, voriconazole) and with cytokine-stimulated granulocyte transfusions. Preventing fusariosis relies on detection and treatment of cutaneous damage prior to commencing immunosuppression and decreasing environmental exposure to Fusaria (via air and water).
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PMID:Human fusariosis. 1474 3

We report the first case of Phialemonium obovatum fungemia with subsequent caseating granulomatas in the lung and Crohn disease-like involvement of the gastrointestinal tract in a bone marrow transplant recipient. This phaeoid fungus has been rarely described as an opportunistic infection in immunosuppressed patients. The patient was diagnosed with chronic myelogenous leukemia and underwent subsequent peripheral bone marrow transplant. After 6 months, he developed graft-versus-host disease of the skin and liver with fever and severe diarrhea. Fecal bacterial cultures and cytomegalovirus serologies were negative. Computed tomographic scan showed a peripheral pulmonary mass. A lung wedge biopsy of the lesion showed septate branching hyphae (4-5 microm in diameter) with terminal globular structures (10 microm in diameter). The hyphae were similar in width to that of an Aspergillus species but had a more moniliform appearance. Blood cultures grew a pure culture of P. obovatum. He was treated with amphotericin B and itraconazole for 6 months without remission of the diarrhea. Biopsies of the stomach, colon, and rectum showed granulomatous inflammation with marked crypt distortion simulating Crohn disease. In retrospect, the fungus was found to be resistant to both of the aforementioned drugs and susceptible to voriconazole and posaconazole. The gastrointestinal findings raise the possibility of further dissemination of a partially treated Phialemonium infection.
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PMID:Lung infection due to opportunistic fungus, Phialemonium obovatum, in a bone marrow transplant recipient: an emerging infection with fungemia and Crohn disease-like involvement of the gastrointestinal tract. 1608 58

Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.
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PMID:Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases. 1758 Feb 55


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