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)

Listeriosis is uncommon in recipients of allogeneic blood, marrow and organ transplantation. Six patients with systemic Listeria monocytogenes infection during 1985-1997 at Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center are described. In two male and four female patients, the median duration from transplantation to isolation of L. monocytogenes was 62.5 (range 29 to 821) days. Among five allogeneic marrow transplant recipients, four (80%) received HLA antigen matched, T cell-depleted grafts from three unrelated and a single related donor. One patient underwent mismatched-related marrow graft transplant. Cord stem cell transplantation was performed in a single patient. Two required therapy for graft-versus-host disease (GVHD). The 13 year incidence of systemic Listeria infections was 0.47 percent. All six presented with fever (>39 degrees C), and L. monocytogenes bloodstream invasion. Mental status changes and meningioencephalitis were observed in two (33.3%). A concurrent primary opportunistic infection was present in five individuals (83.3%), and four (80%) were being treated for acute human cytomegalovirus (HCMV) viremia. Sixty-six percent responded to therapy and two died from unrelated, non-listeric causes. Systemic listeriosis was uncommon in our high-risk allogeneic blood and marrow transplantation population, and response to therapy with parenteral ampicillin and gentamicin was excellent. The association between primary HCMV reactivation and subsequent listeric infection emphasizes the significance of HCMV-related dysfunction in hosts' cellular immune responses, especially in the setting of allogeneic transplantation.
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PMID:Listeriosis in recipients of allogeneic blood and marrow transplantation: thirteen year review of disease characteristics, treatment outcomes and a new association with human cytomegalovirus infection. 1208 Mar 57

Antithymocyte globulin (ATG) preparations in allogeneic stem cell transplantation are used in various conditioning regimens both to prevent graft rejection and reduce the incidence and severity of graft-versus-host disease. Tecelac (RATG) is a highly purified ATG preparation with high specific activity. The high specific antibody content implies the need for lower doses, with reduced side-effects in comparison to other ATGs. Here, we report on the first 10 patients worldwide who received RATG as part of conditioning. Patients were heterogeneous with regard to diagnoses and graft characteristics. RATG was given in cases of matched unrelated donors, mismatched family donors, reduced conditioning, or high risk for graft failure. Mostly mild allergic reactions toward RATG were seen. All of the patients engrafted in due time. Two died within 2 months of transplant of pulmonary complications not related to RATG. Two developed GVHD grade I, no chronic GVHD was seen to date. Viremia occurred in two, with no viral disease developed. Of the eight patients surviving, one suffered relapse of acute leukemia, one shows impending graft failure. The others are well. Using RATG in conditioning is feasible.
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PMID:Tecelac as antithymocyte globulin in conditioning for childhood allogeneic stem cell transplantation. 1209 62

Visceral disseminated varicella-zoster virus (VZV) infection occurred with acute graft-versus-host disease in a 33-year-old Japanese male with non-Hodgkin lymphoma who had undergone allogeneic stem cell transplantation from an HLA-identical sibling after reduced intensity conditioning chemotherapy. Although ganciclovir and acyclovir treatment was effective temporarily, the number of VZV-DNA copies in the blood remained at a high level, and the hepatitis was prolonged. The patient was treated with foscarnet, which led to improvement of the VZV viremia and the hepatic dysfunction. Foscarnet therapy should be considered for acyclovir-resistant VZV infection in the setting of allogeneic hematopoietic stem cell transplantation.
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PMID:[Successful treatment with foscarnet for disseminated varicella-zoster infection after reduced intensity stem cell transplantation in a case of relapsed refractory central nervous system lymphoma]. 1293 63

Nonmyeloablative hematopoietic stem cell transplantation (NST) has been explored in hematological malignancies and solid tumors in an attempt to minimize treatment-related toxicity. Whether this approach is associated with reduced risk of infectious complications is unclear. The aim of the current study was to evaluate the infectious complications in a series of 32 consecutive adult patients who received NST at our institution. Peripheral blood stem cell grafts (n=30) or marrow grafts (n=2) were infused from human leukocyte antibody (HLA)-matched sibling (n=30), partially matched related (n=1), or unrelated (n=1) donors. Neutropenia developed in two-thirds of patients and lasted 16 days. Acute graft-versus-host disease (GVHD) grade II to IV was observed in 25% of patients, whereas 35% of patients had signs of extensive chronic GVHD. Twenty-two patients (69%) had at least one significant infectious episode. Bacteremia occurred in 19% of patients (n=5 gram-positive, n=1 gram-negative microorganisms). Cytomegalovirus (CMV) infection was observed in 10 out of 28 (36%) evaluable patients; 4 of these had recurrent or persistent CMV antigenemia requiring a second-line treatment, but eventually the viremia cleared. No patients experienced CMV disease. Fungal infections were documented in five (16%) patients, comprising invasive fungal infections in two cases and mucosal fungal infections in three. Four patients died of transplant-related causes, and three of these died before day +100. Infection was considered the primary cause of death in one patient (pulmonary aspergillosis) and contributed to death in another two. The actuarial probability of nonrelapse mortality at 100 days was 10% (95% confidence interval, 3-26%). Our preliminary results suggest that NST is associated to a low incidence of bacteremia or fungal and viral infections. Whether these findings would translate into an improved overall survival needs to be confirmed in larger prospective studies.
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PMID:Infectious complications following nonmyeloablative allogeneic hematopoietic stem cell transplantation. 1461 1

The incidence of Epstein-Barr virus (EBV) viraemia and lymphoproliferative disease (LPD) was studied in a consecutive cohort of 128 paediatric patients undergoing stem cell transplantation (SCT) with reduced-intensity conditioning (RIC; n = 65) or conventional-intensity conditioning (CIC; n = 68). Following CIC, six of 68 (8%) developed viraemia; all remained asymptomatic. EBV viraemia (23 of 65 patients = 35%, P < 0.001) and LPD (10 of 65 = 15%, P < 0.001) were significantly more frequent following RIC. Of the 23 RIC patients who developed viraemia, eight remained asymptomatic, five had symptomatic viraemia (fever +/- rash), and 10 patients developed LPD, two of whom died. An absolute lymphocyte count of <0.3 x 10(9)/l at the time of onset of viraemia was strongly predictive of development of LPD (P < 0.05) in this group. The incidence of viraemia was significantly higher in patients receiving serotherapy with antithymocyte globulin (ATG; 15 of 43, 35%) than Campath (12 of 73, 16.4%, P < 0.05). Primary immunodeficiency and acute graft-versus-host disease were associated with EBV viraemia in univariate analysis, but were not independent risk factors. In conclusion, EBV viraemia and LPD appear to be significantly more common in children following RIC SCT, particularly with selective depletion of recipient T cells relative to B cells following the use of ATG. This probably reflects the profound immunosuppression following RIC SCT, together with the incomplete ablation of recipient-derived B cells.
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PMID:Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning. 1581 51

Allogeneic stem cell transplantation is often complicated by reactivation of herpesviruses. Mesenchymal stem cells (MSC) are immunomodulatory and may be used to treat graft-versus-host disease. We investigated if herpesviruses infect and can be transmitted by MSC, and if MSC suppress immune responses to various infectious agents. Mesenchymal stem cells from healthy seropositive donors were evaluated with polymerase chain reaction for the most common herpesviruses: cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, Epstein-Barr virus (EBV) and varicella zoster virus. The cytopathological effect (CPE) was investigated and viral antigens analyzed by immunofluorescence after in vitro exposure to CMV, HSV-1 and EBV. We also studied MSC effect on lymphocyte stimulation induced by various infectious agents. No viral DNA could be detected in MSC isolated from healthy seropositive individuals. However, a CPE was noted and intracellular viral antigens detected after infection in vitro by CMV and HSV-1, but not by EBV. The CMV and HSV-1 infections were productive. Lymphocyte proliferation by herpesviruses, candida mannan and protein A from Staphylococcus aureus was suppressed by MSC. The data indicate that the risk of herpesvirus transmission by transplantation of MSC from healthy seropositive donors is low. However, MSC may be susceptible to infection if infused in a patient with CMV or HSV-1 viremia. MSC transplantation may compromise the host's defense against infectious agents.
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PMID:Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual. 1660 97

The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft-versus-host disease (GvHD). We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin in order to expedite immune reconstitution after a CD3-depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3(+) T-cells, T-cell receptor (TCR) excision circle counts, TCRbeta repertoire diversity and natural killer (NK)-cells during the first 4 months post-transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen appears to accelerate immune recovery and shorten the duration of early post-transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T-cell reconstitution, retention of NK-cells in the graft and induction of low grade GvHD may also enhance the potential anti-cancer immune effect.
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PMID:Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies. 1701 Jan 5

Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantation in children. Recently the incidence, risk factors, and outcome of such infections have been better defined using improved virologic detection methods, in particular polymerase chain reaction. We have introduced intensive virologic surveillance for adenovirus in our institution including at least weekly polymerase chain reaction testing of blood and stool samples. We report on 71 prospectively monitored transplants, including 40 from unrelated donors. In total, there were 8 cases of invasive adenovirus infection, 3 of whom died. Mortality was less than in previous studies as cases were managed with antiviral chemotherapy and reduction of immune suppression. In fatal cases, there was concurrent difficult graft versus host disease making withdrawal of immune suppression therapy impossible. We describe 2 cases of graft failure in association with adenovirus viremia and its treatment that were successfully managed with further donor cell infusion.
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PMID:Improved outcome from invasive adenovirus infection in pediatric patients after hemopoietic stem cell transplantation using intensive clinical surveillance and early intervention. 1727 3

Cytomegalovirus (CMV) infection is an important complication following allogeneic hematopoietic stem cell transplant (HSCT), but the natural history in the cord blood setting has not been well studied. We assessed CMV infection episodes in 753 consecutive allogeneic HSCT recipients at the University of Minnesota between January 1, 1998 and December 31, 2003. The 6-month cumulative incidence of viremia/antigenemia was 22% by day +182: 21% (95% confidence interval 16%-26%) in cord blood recipients (UCB), 24% (20%-28%) in marrow (BM), and 22% (16%-28%) using peripheral blood grafts (PBSC). CMV disease incidence was 6% (2%-10%) in UCB, 8% (5%-11%) in BM, and 9% (6%-12%) in PBSC. In multivariate analysis, CMV infection (viremia/antigenemia and disease) was significantly more likely in patients who were seropositive to CMV, in those with acute graft versus host disease, and in those receiving T cell-depleted grafts. Graft source did not independently contribute to the risk of CMV infection and did not impact survival after CMV infection. These data confirm that recipient CMV serostatus remains the dominant risk factor for CMV infection. Recipients of UCB have similar risks of CMV infection, responses to antiviral therapy, and survival following CMV infection as recipients of either marrow or PBSC.
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PMID:Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. 1769 73

Invasive aspergillosis (IA) remains a major complication following allogeneic hematopoietic stem cell transplant (HSCT). In contrast to conventional HSCT, few investigators have examined risk factors of IA associated with nonmyeloablative (NMA) regimens characterized by outpatient administration, immunosuppression rather than cytoreduction, and short duration of neutropenia posttransplant. We report our results on a cohort of 125 patients treated homogenously who received a 6/6 matched sibling NMA HSCT designed to be performed on an outpatient basis. Conditioning regimen included fludarabine (30 mg/m(2) x 5 days) and cyclophosphamide (300 mg/m(2) x 5 days) followed by reinfusion of a minimum of 4 x 10(6) CD34(+) cells/kg. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil (MMF). Overall, 13 patients developed IA (5 proved, 6 probable, 2 possible) 44-791 days (median 229) after NMA HSCT, with a risk of 7% at 1, 11% at 2, and 15% at 3 years. Patients who suffered from IA had poorer overall survival (crude hazard ratio 2.3; 95% confidence interval [CI] 1.0-5.4; P = .045). Intestinal aGVHD or chronic GVHD (cGVHD) was significantly associated with IA at 1 (27% versus 3%, P = .003), 2 (27% versus 8%, P = .01), and 3 years (37% versus 10%, P = .005). The use of daclizumab was also significantly associated with IA at 3 years (47% versus 12%, P = .02). Age, sex, diagnosis, previous autologous transplant, duration of neutropenia, occurrence of cytomegalovirus viremia, duration of steroids or MMF intake, aGVHD, cGVHD, and cumulative number of days spent in hospital were not associated with IA. After multivariate analysis, intestinal GVHD remained the only statistically significant risk factor for IA at 1 (P = .003), 2 (P = .01), and 3 years (P = .005). We conclude that in NMA HSCT, the risk of IA increases over time and is significantly associated with intestinal GVHD. Because there is currently no surrogate in vitro markers of immunocompetence following NMA HSCT, this clinical finding is of particular importance to identify a population at higher risk who should be targeted for antimold prophylaxis.
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PMID:High incidence of invasive aspergillosis associated with intestinal graft-versus-host disease following nonmyeloablative transplantation. 1788 56


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