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)

Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.
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PMID:Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience. 805 7

We have examined data reported in the AIEOP-BMT Registry in order to determine the incidence, causes and risk factors for fatal pneumopathy after bone marrow transplantation in a pediatric population. Overall, in the Registry 1134 children are reported, 531 of whom received an autologous BMT, 468 allomatched BMT, eight syngeneic, 75 mismatched, 29 unrelated and 23 peripheral blood progenitor cells as rescue after myeloablative therapy in the period 1983-1993. 198 patients out of 1134 (17%) died of transplant-related causes and 86 of them died of pulmonary complications: 12 were recorded as fungal pneumonia, eight bacterial, four bacterial and fungal, six viral, two Pneumocystis carinii pneumonia, 12 ARDS, 13 interstitial, 29 unspecified 'respiratory failure'. Multivariate analysis showed that only type of graft and presence or absence of Pneumocystis carinii prophylaxis influence the cumulative incidence of fatal pneumonia. After autologous BMTs only Pneumocystis carinii prophylaxis was significant in multivariate analysis. After allogeneic BMTs multivariate analysis showed that BMT type, Pneumocystis carinii prophylaxis and GVHD grade seem to maintain their influence on cumulative incidence of fatal pneumonia. After BMT the incidence of fatal pneumopathy in children is low (9%), but it represents the second cause of death after primary disease. Pneumocysti carinii prophylaxis should also be given after autologous BMT.
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PMID:Fatal pneumopathy in children after bone marrow transplantation--report from the Italian Registry. Italian Association of Pediatric Hematology-Oncology BMT Group. 854 64

We retrospectively reviewed all positive Pneumocystis carinii findings among adult patients who had received an allogeneic BM transplant at the Helsinki University Central Hospital between July 1990 and December 1993. The aim was to define the incidence of late onset Pneumocystis carinii pneumonia (PCP) in BMT patients who had routinely received PCP prophylaxis for 6 months post-BMT. In 110 BMT patients, 16 episodes of PCP were documented. Only one patient had been receiving PCP prophylaxis at the onset of PCP. Fourteen of the episodes occurred more than 6 months post-BMT. (median 10.5, range 4-42 months); three of them beyond 1 year. All three had extensive chronic GVHD. Of the 11 patients with an onset between 7-12 months post-BMT, all but one were on methylpredisolone because of chronic GVHD (n = 7) or cytopenia (n = 2) and five of them were in relapse of their hematological malignancy. No mortality from PCP was detected. The risk of developing PCP between 7-12 months post-BMT among patients at risk was 13.4%. We conclude that PCP prophylaxis should be continued until 1 year post-BMT in patients receiving corticosteroid treatment as well as in those with a hematological relapse. Long-term prophylaxis beyond 1 year should be considered in cases with extensive chronic GVHD.
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PMID:Late onset Pneumocystis carinii pneumonia following allogeneic bone marrow transplantation. 880 14

An 8-month-old child with an immunodeficiency disorder characterized by abnormal lymphocyte function and by low IgG and IgA levels had combined liver and small bowel transplantation under tacrolimus and steroid immunosuppression for the treatment of short gut syndrome and hepatic cirrhosis. The patient developed an early postoperative episode of Pneumocystis carinii pneumonia, and a subsequent surgical complication, prompting discontinuance of tacrolimus. A skin rash eventually shown to be graft-versus-host disease (GVHD) developed in the flank on the 12th post-transplant day and gradually became generalized. Peritonitis, sepsis, multisystem organ failure including the liver allograft led to death on the 23rd post-operative day. The mechanisms leading to post-transplant GVHD under the specific circumstances in this case are discussed.
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PMID:Graft-versus-host disease after liver and small bowel transplantation in a child. 936 21

A wide variety of pulmonary complications occur in bone marrow transplant (BMT) recipients and are a major cause of morbidity and death. High-resolution computed tomography (CT) is excellent in the detection of pulmonary abnormalities, but these findings are generally nonspecific. However, the different complications, which reflect the immunologic status of the patients, occur in three phases. This pattern can be used to interpret CT scans. The neutropenic phase (up to 3 weeks after BMT) is characterized by fungal infections, notably angioinvasive aspergillosis, alveolar hemorrhage, pulmonary edema, and drug reactions. At CT, angioinvasive aspergillosis appears as a nodule surrounded by a halo of ground-glass attenuation; alveolar hemorrhage and drug reactions, as bilateral areas of ground-glass attenuation or consolidation; and pulmonary edema, as prominent pulmonary vessels, interlobar septal thickening, ground-glass attenuation, and pleural effusions. The second phase (3 weeks to 100 days after BMT) is dominated by cytomegalovirus pneumonia, which appears as multiple small nodules with associated areas of consolidation or ground-glass attenuation, and Pneumocystis carinii pneumonia, which appears predominantly as ground-glass attenuation. The late phase (more than 100 days after BMT) is characterized by bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia (BOOP), and chronic graft-versus-host disease. In bronchiolitis obliterans, CT reveals bronchial dilatation and a mosaic pattern of attenuation; in BOOP, CT findings usually consist of patchy consolidation or ground-glass attenuation. If CT findings are considered in relation to the time elapsed after BMT, diagnostic options can be narrowed sufficiently to enable accurate diagnosis.
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PMID:Pulmonary complications after bone marrow transplantation: high-resolution CT and pathologic findings. 939 51

Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) is routinely given after allogeneic blood or marrow transplantation. We evaluated the effectiveness of dapsone prophylaxis (50 mg orally twice daily, 3 times per week) compared with twice-weekly trimethoprim-sulfamethoxazole (TMP-SMZ) in preventing PCP after allogeneic blood or marrow transplantation. Patients included all (n=646) who received allogeneic blood or marrow transplants between 1 September 1993 and 31 December 1996 who survived at least 100 days after transplantation. A cohort of 111 dapsone recipients was compared with the remaining 535 who received TMP-SMZ. Ten patients developed PCP; 8 were taking dapsone. PCP incidence in the TMP-SMZ cohort was 0.37% versus 7.2% for dapsone. The relative risk for PCP associated with dapsone use was 18.8 (P<.001) and was not accounted for by age, clinical extensive chronic graft-versus-host disease, donor source, or malignant relapse. Dapsone prophylaxis at this dosage is associated with significantly higher rates of PCP than is TMP-SMZ after allogeneic marrow transplantation. We advise caution in prescribing alternatives to TMP-SMZ prophylaxis in this setting.
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PMID:High rates of Pneumocystis carinii pneumonia in allogeneic blood and marrow transplant recipients receiving dapsone prophylaxis. 1058 97

Pneumocystis carinii pneumonia (PCP) is a life-threatening but preventable infection that may occur after bone marrow transplantation (BMT). Although various prophylactic regimens have been used in this setting to prevent active infection, their efficacy, toxicity profile, and impact on outcomes are poorly described in this patient group. We undertook a retrospective cohort study in which we reviewed the records of 451 adult patients who underwent BMT for hematologic malignancies, aplastic anemia, or myelodysplasia over a 7-year period at the Brigham and Women's Hospital. Post-BMT PCP prophylaxis consisted of aerosolized pentamidine (AP) 150 mg every 2 weeks or 300 mg per month, trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg orally b.i.d. 3 times per week, or dapsone 100 mg orally each day. Prophylaxis was continued for 1 year post-BMT in all patients when clinically feasible. One hundred twenty-one patients were unevaluable because of death or relapse <60 days after BMT (n = 89), loss to follow-up upon hospital discharge (n = 20), or other reasons (n = 12). Three eligible patients did not receive any prophylaxis and were not further evaluated. Of the 327 patients analyzed, 133 underwent autologous BMT, 4 syngeneic BMT, 159 related allogeneic BMT, and 31 unrelated allogeneic BMT. Graft-versus-host disease prophylaxis in the 190 patients receiving allogeneic BMT consisted of T-cell depletion with anti-CD5 and complement in 58 patients and cyclosporine/methotrexate or FK506 with or without steroids in 132 patients. Eight of 327 (2.4%) documented PCP cases were identified, 0 of 105 in patients receiving only TMP/SMX. Four cases occurred in patients receiving only AP (4/44, 9.1%; odds ratio [OR] relative to TMP/SMX 23.4, 95% confidence interval [CI] 1.2, 445.2); 1 in patients receiving only dapsone (1/31, 3.2%; OR not significant); 2 in patients receiving more than 1 prophylactic regimen (2/147 1.4%; OR not significant); and 1 >1 year post-BMT in a patient who was off PCP prophylaxis. Although the patients receiving only AP had a significantly lower probability of treatment-related toxicity than those receiving TMP/SMX (OR 0.19 [95% CI 0.04, 0.851), the probability of their acquiring other serious non-PCP infections was increased (OR 2.2 [95% CI 1.0, 4.6]), and the probability of their dying by 1 year post-BMT was significantly higher (OR 5.2 [95% CI 2.4, 26.6]), even when adjusted for variables such as type of BMT (autologous versus allogeneic; high versus low risk) and sex. Although AP is associated with fewer toxicities, the data show that it is inferior to TMP/SMX in preventing PCP in the post-BMT setting and is associated with an increased risk of other infections and a higher mortality at 1 year after BMT.
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PMID:Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections. 1070 97

Although allogeneic transplantation is a curative therapy for chronic myelogenous leukemia (CML), treatment-related mortality is still a major cause of death after transplantation, especially in older patients. We investigated the safety and efficacy of reduced-intensity conditioning consisting of low-dose (600 cGy) total body irradiation and cytosine arabinoside (1 g/m2) together with a continuous infusion of granulocyte colony-stimulating factor and cyclophosphamide (120 mg/kg) in patients with CML in the chronic phase. Fractionated splenic irradiation (5 Gy) was also administered as part of the conditioning treatment. Eight patients older than 40 years underwent allogeneic bone marrow transplantation from an HLA-matched sibling following this conditioning. Regimen-related toxicities (equal to or greater than grade III) were not observed. Rapid restoration of 100% donor chimerism was confirmed by fluorescence in situ hybridization methods in 5 sex-mismatched transplant recipients. One patient died from severe acute graft-versus-host disease and another from Pneumocystis carinii pneumonia early in the course of transplantation. A sustained engraftment was achieved in 5 long-term survivors; in 1 case, the graft was rejected but the Philadelphia chromosome and BCR/ABL-negative autologous hemopoiesis were restored. After a minimum follow-up period of 60 months, 6 patients, including the patient with restored autologous hemopoiesis, were still alive and in remission with 100% donor chimerism. Six years after the transplantation, 1 patient experienced a cytogenetic relapse, which was successfully treated with donor lymphocyte infusions. In summary, this reduced-intensity conditioning resulted in a cure with markedly reduced regimen-related toxicities in this relatively older cohort of patients with CML.
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PMID:Long-term follow-up of allogeneic bone marrow transplantation after reduced-intensity conditioning in patients with chronic myelogenous leukemia in the chronic phase. 1209 49

The incidence, etiology, outcome, and risk factors for developing pneumonia late after hematopoietic stem cell transplantation (SCT) were investigated in 1359 patients transplanted in Seattle. A total of 341 patients (25% of the cohort) developed at least one pneumonic episode. No microbial or tissue diagnosis (ie clinical pneumonia) was established in 197 patients (58% of first pneumonia cases). Among the remaining 144 patients, established etiologies included 33 viral (10%), 31 bacterial (9%), 25 idiopathic pneumonia syndrome (IPS, 7%), 20 multiple organisms (6%), 19 fungal (6%), and 16 Pneumocystis carinii pneumonia (PCP) (5%). The overall cumulative incidence of first pneumonia at 4 years after discharge home was 31%. The cumulative incidences of pneumonia according to donor type at 1 and 4 years after discharge home were 13 and 18% (autologous/syngeneic), 22 and 34% (HLA-matched related), and 26 and 39% (mismatched related/unrelated), respectively. Multivariate analysis of factors associated with development of late pneumonia after allografting were increasing patient age (RR 0.5 for <20 years, 1.2 for >40 years, P=0.009), donor HLA-mismatch (RR 1.6 for unrelated/mismatched related, P=0.01), and chronic graft-versus-host disease (GVHD; RR 1.5, P=0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted.
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PMID:Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation. 1294 99

CD40 ligand (CD40L) deficiency causes recurrent sinopulmonary infection, Pneumocystis carinii pneumonia, and Cryptosporidium parvum infection. Approximately 40% to 50% of patients survive to the third decade: long-term survival is unclear. Hematopoietic stem cell transplantation (HSCT) is curative. We present a retrospective analysis of 38 European patients undergoing HSCT for CD40L deficiency in 8 European countries between 1993 and 2002. Donor stem cell source included 14 HLA-identical siblings, 22 unrelated donors, and 2 phenotypically matched parental stem cells (12 T-cell depleted). Of the patients, 34 engrafted and 26 (68%) survived; 3 had autologous reconstitution, 22 (58%) were cured, and 1 engrafted but has poor T-cell immune reconstitution. There were 18 evaluated patients who responded to vaccination. Of the patients, 12 (32%) died from infection-related complications, with severe cryptosporidiosis in 6. Grades 2 to 4 graft-versus-host disease (GvHD) associated with infection occurred in 6 of 12 fatal cases. HSCT cured 58% of patients, 72% of those without hepatic disease. Early T-cell function following whole marrow HSCT may limit cryptosporidial disease, but survival was similar after T-cell-depleted HSCT. Preexisting lung damage was the most important adverse risk factor. Further studies will determine optimal timing and type of HSCT.
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PMID:Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002. 1452 61


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