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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)

Infection with HCMV in healthy individuals generally results in mild or subclinical illness. Pathogenic infections occur predominantly in immunodeficient patients, such as transplant recipients, neonates and patients with AIDS. Primary infection is frequently latent or chronic and PBLs represent sites for virus latency and persistence. HCMV can be recovered from PMNL, monocytes and T-lymphocytes. Although virus-related cases of haematopoietic dysfunction are seen infrequently in infected normal persons, the importance of HCMV as a pathogenic agent in haematopoiesis is dramatically illustrated in the case of patients receiving BMT. Primary or reactivated HCMV infections are a common feature in BMT recipients, enhancing failure of marrow engraftment, GVHD, and many opportunistic infections. HCMV can infect both haematopoietic progenitor cells and stromal elements, identifying the entire haematopoietic system as a target for HCMV dissemination and latency. As a result, lympho- and myelosuppression can be due to both direct inhibition of progenitor cell growth as well as the failure of stem cell self-renewal due to stromal cell dysfunction. HCMV can also exert suppressive effects on immune cell function by direct and indirect mechanisms. These effects can have dire consequences, particularly when a state of immunosuppression already exists, as in the HIV infection. The diverse effects of CMV on the lymphohaematopoietic system are summarized in Figure 1.
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PMID:The role of human cytomegalovirus in haematological diseases. 766 45

Infections and graft-versus-host disease are the major causes of morbidity and mortality in bone marrow transplantation (BMT). Bacterial infections can nowadays be treated effectively in most instances. The prophylactic and therapeutic armamentarium for viral infections is improving. Fungal infections on the contrary remain a major obstacle for successful outcome in the transplant situation. Invasive fungal infections are mainly caused by Candida and Aspergillus spp. and more seldom by Mucor, Trichosporon and Fusarium. Invasive fungal infections are notoriously difficult to diagnose early and effective non-toxic treatments are still out of reach. Prophylaxis for Candida albicans has become more effective with new triazoles but for species other than albicans and for Aspergillus spp. prophylaxis still remains a major problem. Better treatment modalities, more effective prophylaxis and better knowledge of risk factors are urgently needed. The recently created Invasive Fungal Infections Cooperative Group of the EORTC chaired by Professor F. Meunier runs different surveys to investigate the incidence and nature of invasive fungal infections in cancer patients and in BMT. The group runs different clinical trials on the prophylaxis and treatment of invasive fungal infections.
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PMID:Epidemiology of invasive fungal infections in bone marrow transplantation. EORTC Invasive Fungal Infections Cooperative Group. 770 24

We have reviewed the causes and risk factors for early death in a group of 295 children who underwent any form of first bone marrow transplantation (BMT) between 1978 and 1992. The commonest indications for transplantation were acute lymphoblastic leukaemia 80 (27.1%), neuroblastoma 69 (23.3%), immune deficiency 57 (19.3%) and myeloid leukaemias/myelodysplasia 50 (16.9%). There were 120 (40.6%) allogeneic BMTs, 118 (40%) autologous BMTs, while 51 (17.2%) children usually with severe combine immune deficiency received BMT from a non-HLA-identical parent, sibling or other relative (FBMT). Two were from identical twins and four from matched unrelated donors (MUD). Thirty-three children (11.2%) died in the first 100 days; the main causes of death being infection (n = 5), relapse (n = 7), graft failure (n = 4), GVHD (n = 7) and organ failure with or without infection (n = 6). There was no significant change in the incidence of early deaths in the three successive 5 year periods (1978-82, 1983-87, 1988-92) although there was some shift in the causes. Infections were the commonest cause during the first 5 year period, relapses followed by GVHD in the second period and single organ failure followed by GVHD and infections in the third period. The main causes of early death were relapse after high-dose chemo/radiotherapy and autologous BMT (7 of 9 deaths) and GVHD and infection after allogeneic BMT (9 of 13 deaths). In the group of 51 children undergoing FBMT there were five deaths from infection, three from graft failure, one from organ failure and one from GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early deaths in children undergoing marrow ablative therapy and bone marrow transplantation. 771 76

The availability of hematopoietic growth factors has introduced a new therapeutic modality to the treatment of graft failure after bone marrow transplantation (BMT). However, the clinical value of other therapeutic approaches to graft failure has not been reported in detail. We have studied the outcome of second infusions of BM for treatment of primary and secondary graft failure in 33 patients who received an allogeneic BMT at our institution between 1974 and 1992. Patients had received BM from a related (n = 28) or unrelated (n = 5) donor for hematological malignancy or BM failure. After primary graft failure, 57% (12 of 21) of reinfused patients engrafted and the Kaplan-Meier estimate of survival at 1 year is 24% (CI 6-42%). After secondary graft failure, 33% (4 of 12) of reinfused patients engrafted and survival is 25% (CI 0-50%) at 1 year. Infection, predominantly fungal, was the most frequent cause of death. Acute or chronic graft-versus-host disease (GVHD) developed in 52% of evaluable reinfused patients. We conclude that reinfusion of donor marrow can be an effective intervention in the treatment of primary and secondary graft failure. These data can serve as a comparative historical experience for the assessment of hemopoietic growth factors in the treatment of graft failure.
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PMID:Second infusion of bone marrow for treatment of graft failure after allogeneic bone marrow transplantation. 795 Nov 23

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

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

Abdominal problems and catastrophes often complicate the clinical course after bone marrow transplantation (BMT) in children. These complications can be grouped into categories of infection, chemotherapy and radiation toxicity, graft-versus-host disease (GVHD), recurrent or de novo malignancy, and miscellaneous complications and can involve the hepatobiliary system, pancreas, spleen, gastrointestinal tract, and urinary tract. Infection is common after BMT: the causative organism depends on the changing immunologic state of the recipient and even on environmental factors such as recent construction, humidity, and antibiotic use. Chemotherapy and radiation therapy can cause hepatic veno-occlusive disease, pancreatitis, nephritis, and hemorrhagic cystitis. GVHD is a process in which donor lymphoid cells produce damage to recipient target organs, especially skin, liver, and intestinal mucosa. Recurrent or de novo disease or malignancies, particularly B-cell lymphomas, may develop in chronically immunocompromised children. Other problems include stone disease, splenic and renal infarction, and complications of hyperalimentation therapy. Abdominal imaging, including plain radiography, contrast material-enhanced studies of the bowel, real-time and duplex sonography, and computed tomography, is essential in diagnosing these problems and evaluating response to therapy.
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PMID:Abdominal complications in pediatric bone marrow transplant recipients. 821 May 93

Between June 1988 and February 1993, combined heart-lung transplantation was performed in 30 children and adolescents aged 3.6 to 18.6 years (mean, 12.2 years) at The Hospital for Sick Children in London. Original diagnoses included cystic fibrosis (n = 25), Eisenmenger's syndrome (n = 4), and chronic graft-versus-host disease of the lung (n = 1). Posttransplantation maintenance immunosuppression comprised a triple regimen, with methylprednisolone and antithymocyte globulin given perioperatively and for episodes of allograft rejection. Actuarial survival was 63% (95% confidence interval: 42%-78%) at 1 year and 48% (95% confidence interval: 27%-66%) at 3 years. Obliterative bronchiolitis has been diagnosed in 13 patients (43%). Actuarial freedom from obliterative bronchiolitis in survivors was 76%, 59%, and 37% at 12, 24, and 36 months after transplantation, respectively. Recipients in whom obliterative bronchiolitis developed within the first year (n = 6) had more episodes of pulmonary rejection during the first 6 months after transplantation (mean, 5.7 episodes per patient) than those in whom "premature" obliterative bronchiolitis did not develop (mean, 3.2 episodes per patient). Infection of the pulmonary allograft was implicated to a lesser extent in predisposing to obliterative bronchiolitis. At 2, 3, and 6 months, tracheal stenosis developed in three patients, all of whom died with obliterative bronchiolitis within 10 months of transplantation. Noncompliance with therapy was considered a contributory factor in producing obliterative bronchiolitis in four adolescent recipients. The high incidence of obliterative bronchiolitis observed in this pediatric cohort may have a multifactorial cause.
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PMID:Incidence of obliterative bronchiolitis after heart-lung transplantation in children. 831 13

The pathological complications of bone marrow transplantation are complex and may affect any organ in the body. The causes are often multifactorial and include the effects of chemotherapy, the conditioning regimen, drugs used in the post-transplant period such as immunosuppressants and antibiotics, graft-versus-host disease (GvHD) and the effects of the primary disease itself. Infections are common and result from the immunosuppressive effects of cytotoxic drugs and irradiation, GvHD and marrow failure. Haemorrhage is not infrequent. Graft-versus-host disease remains a significant problem and can be difficult to diagnose. Some of its histological features simulate the effects of chemoradiation and the diagnostic lesions may not be present early in the disease, when treatment is most effective. Evidence has accumulated that inflammatory cytokines have a key role in the pathogenesis of GvHD. It can be prevented by eliminating T-cells from the donor marrow but this procedure adversely affects marrow engraftment, increases the changes of rejection and results in a higher incidence of leukaemic relapse. Immunohistochemical staining for various cytokine-inducible molecules has led to some improvement in early diagnosis.
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PMID:The pathology of bone marrow transplantation. 849 53

We describe the clinical course of idiopathic pneumonia diagnosed by lung biopsy after allogeneic marrow transplantation and the associations of clinical presentation with outcome. All allogeneic marrow transplant recipients with an open-lung biopsy at a single marrow transplantation research center between January 1983 and December 1988 who were without infection were reviewed as a case series (n = 41). Data were retrieved from clinical information routinely collected at the time of transplantation on all patients. The onset of pneumonia was 11 to 143 days after transplant (mean 35), and 93% of cases displayed diffuse pulmonary infiltrates. Overall in-hospital mortality was 71% (n = 29). The case fatality rate was 59% (n = 24): 13 patients (32%) died with progressive respiratory failure, and the other 11 fatalities (27%) died either with recurrent respiratory failure after initial improvement (n = 7) or from nonpulmonary causes without resolution of pneumonia (n = 4). Infection was a major complication and was present at autopsy in 11 of 16 cases (69%). Of 12 patients discharged from the hospital 6 died within 1 yr, most commonly with relapse of malignancy. Both receipt of total-body irradiation > 1,200 cGy and presence of acute graft-versus-host disease were associated with an increased rate of resolution of pneumonia. The overall mortality of idiopathic pneumonia after allogeneic marrow transplantation is high, but less than one-third of patients die of progressive respiratory failure related to idiopathic pneumonia. Infection is commonly associated with death in marrow recipients previously diagnosed with idiopathic pneumonia by lung biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical course of idiopathic pneumonia after bone marrow transplantation. 850 50


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