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)

A 37-year-old female highly alloimmunized by multiple transfusions received a sex matched HLA-identical unrelated bone marrow transplant for hypoplastic MDS-RA with moderate myelofibrosis. Conditioning consisted of total body irradiation, cyclophosphamide and ATG, GVHD prophylaxis consisted of CsA, MTX and prednisolone. The CD34+ stem cell content of the first graft was relatively low due to an inadequate harvest. The patient appeared not to have engrafted by day 23 post-BMT. She therefore received a second sex mismatched HLA-identical unrelated bone marrow graft on day 25 after two days of 3.5 mg/kg methylprednisolone from a different donor. Over the ensuing days, the first marrow showed slow engraftment followed by engraftment of the second graft. The first graft was then rejected, as monitored by peripheral blood studies of chimerism. No signs of acute GVHD were observed. Despite successful trilineage engraftment and complete second donor chimerism, the patient died from disseminated toxoplasmosis encephalitis and pneumonia on day +104.
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PMID:Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure. 948 60

In a 34-year-old patient toxoplasma retinitis/encephalitis developed 9 months after bone marrow transplantation. The BMT was complicated with a serious GVHD. Although she initially responded well to antibiotic therapy she died 2 years after BMT due to progressive infection.
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PMID:Toxoplasma retinitis/encephalitis 9 months after allogeneic bone marrow transplantation. 954 70

A complex pattern of neurological dysfunctions with generalized seizures and visual allucinations, but without focal signs, suddenly arose 20 days after an unrelated bone marrow transplant for chronic myelogenous leukemia (CML) in a 13-year-old girl, accompanied by signs of acute skin graft-versus-host disease (GVHD). Magnetic resonance imaging (MRI) revealed multiple bilateral foci of signal abnormalities, which were exclusively localized in the grey matter, sparing the white. Extensive microbiological and virological assays of cerebrospinal fluid (CSF) allowed the identification of HHV-6, variant A, DNA. Further progression of both neurological alterations and of skin and gut GVHD led to a fatal outcome 2 weeks later. A retrospective analysis of both the recipient and donor mononuclear cell suspensions supported the hypothesis that HHV-6 had been acquired from the donor with the bone marrow graft. This report suggests a pathogenetic role of HHV-6 in viral encephalitis in immunocompromised bone marrow transplant (BMT) recipients, and its possible association with GVHD.
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PMID:Fatal herpesvirus 6 encephalitis after unrelated bone marrow transplant. 972 Jul 44

Posttransplant infection associated with host immune deficiency is the major cause of nonrelapse mortality of human bone marrow transplant recipients. In a new murine model of posttransplant infection, allogeneic bone marrow transplant recipients were infected with herpes simplex virus-1 (HSV-1) via intraperitoneal inoculation 12 weeks after transplantation. Allogeneic transplant recipients with graft-versus-host disease (GVHD) had significantly increased mortality from HSV-1 encephalitis, with deficiencies of both specific anti-HSV-1 antibody and total serum IgG2a. GVHD mice displayed a Th2 cytokine profile (increased interleukin-4 [IL-4] and decreased interferon-gamma) and decreased lipopolysaccharide (LPS) responses, suggesting that both T-cell and B-cell defects contributed to the impaired production of antibody. Because passive transfer of hyperimmune serum protected mice from HSV-1 infection, we hypothesized that CD40 ligand (CD40L), which induces B-cell maturation, would protect mice from HSV-1 infection. CD40L-treated GVHD mice showed elevated IgG2a levels and increased survival compared with vehicle-treated transplant recipients.
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PMID:Recombinant CD40L treatment protects allogeneic murine bone marrow transplant recipients from death caused by herpes simplex virus-1 infection. 983 55

Human herpesvirus 6 (HHV-6) infections following bone marrow transplantation (BMT) have been shown to be associated with fever, skin rash, graft versus host disease, encephalitis, delay in engraftment, marrow suppression, and pneumonia. Unfortunately several of these studies were case reports and although the results were suggestive they prompted us to study these pathological events systematically. These associations were primarily based on either HHV-6 isolation, HHV-6 DNA detection, antigen detection or increases in HHV-6 specific antibodies. HHV-6 activity was more frequent during the post- rather than the pre-transplantation period. All HHV-6 isolates from BMT patients have been shown to be variant B. A better understanding of HHV-6 associated pathogenesis gained by larger prospective trials is needed to facilitate proper treatment of cases of idiopathic illnesses or those associated with symptoms (fever, skin rash) similar to those caused by HHV-6.
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PMID:Human herpesvirus 6 infection and associated pathogenesis following bone marrow transplantation. 986 89

We retrospectively identified opportunistic CNS infections in 655 patients who had undergone allogeneic, syngeneic or autologous BMT or PBSCT between 1990 and 1997. Twenty-seven patients (4%) developed CNS infections. All CNS infections occurred in allogeneic BMT or PBSCT patients. The most common CNS infections were toxoplasma encephalitis (74%) and cerebral aspergillosis (18%). Furthermore, we identified one patient with candida encephalitis and one patient with viral encephalitis. Overall mortality of patients with opportunistic CNS infection was 67%. There were two different groups of toxoplasma encephalitis with a different appearance on MR imaging. The first group showed edema, but no gadolinium enhancement, whereas the second group exhibited typical MRI appearances with the exception of frequent hemorrhagic transformation. The first group had a significant shorter latency between BMT and onset of CNS infection (mean 45 days vs 180 days, P = 0.02), a significant higher daily dose of corticosteroids as treatment for graft-versus-host disease (GVHD) (P = 0.01), more severe GVHD and a higher mortality (71% vs 36%). This study shows that the most common CNS infections in our patient population are toxoplasma encephalitis and cerebral aspergillosis, that there are two distinct subgroups of toxoplasma encephalitis and that CNS infections occur after allogeneic BMT only.
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PMID:Opportunistic CNS infection after bone marrow transplantation. 1038 57

Human herpesvirus-6 (HHV-6), like all the other herpes viruses, remains latent in host cells after primary infection but can be reactivated in immunocompromised patients causing fever, skin rash, bone marrow (BM) suppression, pneumonitis, sinusitis and meningoencephalitis. We describe the case of a man with chronic myelogenous leukemia who developed encephalitis associated with acute graft-versus-host disease two months after a T-cell-depleted mismatched peripheral blood stem cell transplant. Magnetic resonance images of the brain revealed multiple bilateral foci of signal abnormality. HHV-6 was the only pathogen detected in cerebrospinal fluid by PCR. Treatment with both ganciclovir and foscarnet was unsuccessful and the patient gradually deteriorated and died. Other cases of HHV-6 encephalitis after bone marrow transplantation are reviewed.
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PMID:Fatal herpesvirus-6 encephalitis in a recipient of a T-cell-depleted peripheral blood stem cell transplant from a 3-loci mismatched related donor. 1062 99

Reactivation of varicella zoster virus (VZV) is a common event in patients undergoing allogeneic bone marrow transplantation (BMT) and may lead to life-threatening complications. We retrospectively analyzed the incidence, clinical outcome, and risk factors for VZV infections occurring within the first 5 years of transplantation in 100 consecutive adults undergoing allogeneic BMT between 1992 and 1997. Forty-one patients (41%) developed VZV reactivation a median of 227 days (range 45-346 days) post-transplantation. Twelve percent of VZV reactivation occurred in the first 100 days and 88% within the first 24 months. Among those who survived for 2 or more years after transplantation (n = 47), 59% developed VZV infection. Forty percent of patients with VZV reactivation required admission with a mean hospital stay of 7.2 days. Two patients developed encephalitis, and 1 died despite antiviral therapy. The most frequent complications were post-herpetic neuralgia and peripheral neuropathy (68%). Thoracic dermatomal zoster represented 41% of the infections; disseminated cutaneous involvement was observed in 17% of patients. No clinical or epidemiologic risk factors were associated with recurrence. Administration of ganciclovir for prevention of cytomegalovirus infection delayed the onset of VZV infection beyond 4 months (P = .06). In a further subset analysis, patients with a limited chronic graft-versus-host disease (GVHD) had a lower estimated incidence of VZV reactivation compared with those with extensive chronic GVHD (P = .11). We conclude that complications from reactivation of VZV infection are common and associated with considerable morbidity and mortality in patients undergoing allogeneic BMT.
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PMID:Varicella zoster virus infections following allogeneic bone marrow transplantation: frequency, risk factors, and clinical outcome. 1070 98

Adenovirus infections have been reported in as many as one-fifth of bone marrow transplant (BMT) recipients and patients with acquired immunodeficiency syndrome (AIDS), and in a lesser, though still prominent, proportion of organ transplant recipients. The relative contributions of primary infections versus reactivations from latency in immunocompromised patients remain unclear. Compared with adult BMT recipients, pediatric BMT recipients appear to be infected by adenovirus more frequently and earlier in the post-transplant period. The diagnosis of adenovirus infection is complicated by the existence of > 40 viral serotypes, although certain subgroups are more likely to be involved in certain patient populations. Adenoviruses are responsible for a broad range of clinical diseases that may be associated with high mortality, including pneumonia, hepatitis, encephalitis, hemorrhagic cystitis, and gastroenteritis. The clinical and histopathologic features of adenovirus disease may resemble those of cytomegalovirus disease, potentially complicating the diagnosis. Risk factors for clinical adenovirus disease include the number of sites from which the virus is cultured and, in BMT recipients, the presence of moderate to severe acute graft-versus-host disease.
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PMID:Adenovirus infections in immunocompromised patients. 1086 46

Infections with the beta-herpesviruses human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) are ubiquitous in childhood. The immunosuppression secondary to organ or bone marrow transplantation together with posttransplantation management may favour viral replication and reactivation. HHV-6 and -7 induce immunosuppression by targeting lymphocytes, natural killer cells and monocytes. HHV-6 is commonly detected posttransplantation but variability in definitions of clinical syndromes related to this virus and detection methods have complicated understanding of the clinical relevance of HHV-6 posttransplantation. Clinical symptoms associated with HHV-6 include febrile illness, pneumonitis, hepatitis, encephalitis and bone marrow suppression. However, the majority of HHV-6 infections are asymptomatic. The incidence of HHV-7 infection and its clinical manifestations posttransplantation are even less well characterised. In addition, HHV-6 and HHV-7 are related to CMV disease or acute graft-versus-host disease and, indirectly, to increases in resource utilisation. Based on the potential relevance of these two beta-herpesviruses in transplant recipients, further studies are required to establish their real impact in transplantation. For this, sensitive and specific molecular diagnostic techniques allowing for the rapid detection and quantitation of virus and for the analysis of susceptibility to current antiviral agents are required.
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PMID:Human herpesvirus-6 and -7 in transplantation. 1124


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