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)

Allogeneic stem cell transplantation (SCT) can cure several nonmalignant diseases in children. However, patients frequently have significant morbidity before transplantation and there is a high transplant-related mortality. Nonmyeloablative SCT might achieve the same goals but with less toxicity. Six pediatric patients with nonmalignant diseases underwent nonmyeloablative SCT from different stem cell sources. All patients were conditioned with fludarabine/melphalan with additional anti-thymocyte globulin for haploidentical grafts and prophylaxis for graft-versus-host disease (GVHD) consisting of tacrolimus and methotrexate with additional prednisolone for haploidentical grafts. Hematopoietic stem cells were neither T-cell depleted nor purged. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. Five of the six are alive and in complete disease resolution at a median of 19 months (range, 7-53 months) after SCT. One patient died of bacteremia before engraftment. Three patients achieved complete donor chimerism. Two patients remained stable mixed chimerism. Short-term toxicities were minimal. Acute and chronic GVHD were not seen. In summary, the fludarabine-based nonmyeloablative regimen followed by SCT provides a good approach for children with nonmalignant diseases. Even patients with severe organ dysfunctions had adequate engraftment with acceptable toxicities.
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PMID:Nonmyeloablative stem cell transplantation for nonmalignant diseases in children with severe organ dysfunction. 1701 27

Fludarabine-based conditioning (FBC) was given to 24 patients and conventional myeloablative conditioning (MC) to 33 patients, most children, before hematopoietic stem cell transplantation (HSCT) for non-malignant diseases. The donors were human leukocyte antigen (HLA)-A, -B, -DRbeta1-identical related (33%) or unrelated (67%). In the FBC group, two grafts failed versus three in the MC group; all were successfully regrafted. Fever was more common in the MC patients (P=0.003). Bacteremia occurred in 25% of the FBC group and 50% in the MC group (P=0.1). In the FBC group, platelet engraftment was faster and transfusions were fewer (P<0.05). Mucositis and renal function were similar in the two groups. The MC group had higher maximum bilirubin (P=0.03) and less often normal spirometry (P=0.04) after HSCT. A 7-year-old girl in the MC group had permanent alopecia. No patients had severe acute graft-versus-host disease (GVHD). Chronic GVHD was rare. Complete donor CD3+ chimerism was more common in the MC group (P=0.01), but CD33+ engraftment was better with FBS (P=0.03). Treatment-related mortality was 4 and 15%, and 5-year survival was 89 and 85% in the FBC and MC groups. Although survival was similar, FBC is a promising alternative to MC in non-malignant disorders.
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PMID:Fludarabine-based disease-specific conditioning or conventional myeloablative conditioning in hematopoietic stem cell transplantation for treatment of non-malignant diseases. 1731 Jan 37

Streptococcus pneumoniae infections can cause serious systemic disease in patients following hematopoietic stem cell transplantation (HSCT), and the response to pneumococcal vaccine is inadequate in most HSCT recipients. We evaluated the clinical spectrum of pneumococcal disease and vaccine-breakthrough infections in HSCT recipients at our cancer center in a retrospective analysis of all consecutive episodes of S. pneumoniae infection from 1989 through 2005. During the study period, 7888 patients underwent HSCT at our center; we identified 47 HSCT recipients with 54 S. pneumoniae infections. The overall incidence of S. pneumoniae infection was 7 per 1000 HSCTs. The incidence was higher in recipients of allogeneic grafts than in recipients of autologous grafts (9 vs. 5 per 1000 HSCTs, respectively; p <or= 0.012). Thirty-two of the 47 patients (68%) had leukemia or lymphoma; 24 patients (51%) had a malignancy that was in complete remission. Seventeen patients (36%) had graft-versus-host disease, which was chronic in 16. The 54 episodes of S. pneumoniae infection occurred 433 +/- 669 days after HSCT; 5 patients (11%) had multiple episodes. Four episodes of S. pneumoniae infection occurred within 100 days following transplantation (45 +/- 49 d); 2 of these were during the pre-engraftment period and 3 were nosocomial infections. All 50 late post-transplant episodes (93%), which occurred 473 +/- 671 days following transplantation, were community-acquired infections (p < 0.00016). Thirty-three episodes (61%) presented as bacteremic pneumonia, 10 (19%) as pneumonia, and 8 (15%) as uncomplicated S. pneumoniae bacteremia alone. Logistic regression analysis showed that patients receiving systemic corticosteroids had increased risk for bacteremic pneumonia (odds ratio [OR], 11.7; 95% confidence intervals [CI], 1.371-99.280; p <or= 0.025). Patients with lymphoma (OR, 6.101; 95% CI, 1.106-33.640; p <or= 0.04) were more likely to develop pneumonia alone. In 27 episodes (93%) among 29 in which S. pneumoniae susceptibility testing was performed, the patients received concordant antimicrobials. Among the 6 patients (13%) who died of S. pneumoniae infection, 4 had S. pneumoniae bacteremic pneumonia and only 1 had chronic GVHD. Admission to a critical care unit at the onset of infection (OR, 15.5; 95% CI, 2.116-113.541; p <or= 0.007) and each unit increase in APACHE II score increase the probability of death (OR, 1.9; 95% CI, 1.181-3.054; p <or= 0.008). All 5 (11%) patients who developed vaccine-breakthrough S. pneumoniae infection (546 +/- 732 d following vaccination) had pneumonia, and in 4 patients concurrent bacteremia also occurred. A serious S. pneumoniae infection in HSCT recipients occurred more commonly in patients with lymphoma and patients receiving high-dose systemic corticosteroid therapy. It is noteworthy that there were no cases of extrapulmonary organ infection in HSCT recipients who presented with S. pneumoniae infection at our institution.
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PMID:Streptococcus pneumoniae infections in 47 hematopoietic stem cell transplantation recipients: clinical characteristics of infections and vaccine-breakthrough infections, 1989-2005. 1743 87

Severe hemorrhagic cystitis (HC) may be a life-threatening complication in allogeneic stem cell transplantation (SCT). In order to improve the strategies for prophylaxis and treatment, we retrospectively analyzed data on patients who underwent SCT at our center from 1990 through 2005. Patients with HC were identified through our database and their medical charts were reviewed. Grades 2-5 and 3-5 HC developed in 109/834 patients (13.1%) and 27/834 patients (3.2%), respectively. The frequency of HC decreased over the time from 18.0% in 1990-1992 to 9.5% in 2002-2005 (p = 0.005). HC started on a median of 35 (0-166) days post-transplant and persisted for a median of 23 (2-270) days. Transplant-related mortality was 21% in patients without HC, 15% in those with HC of grade 2, 55% in those with grade 3, and 71% in patients with HC of grades 4-5 (p < 0.001). In multivariate analysis, the risk factors for HC were myeloablative conditioning, busulphan, cytomegalovirus infection, hematological malignancy, and acute graft-versus-host disease (aGVHD). With four risk factors, the risk of HC development was 31%. Risk factors for severe HC of grades 3-5 were aGVHD and bacteremia.
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PMID:Hemorrhagic cystitis: a retrospective single-center survey. 1784 42

To assess infectious complications associated with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced- and conventional-intensity conditioning regimens (RIC, n=91; CIC, n=54, respectively), we retrospectively analyzed data from 145 consecutive patients with cGVHD after allogeneic HSCT from a human leukocyte antigen-matched related or unrelated donor. In the present retrospective analysis, 57% (83/145) of patients with cGVHD developed infections, with a mortality rate of 27% (22/83). The incidences of bacteremia (n=28), central venous catheter-related infections (n=11), bacterial pneumonia (n=4), invasive aspergillosis (n=7), and adenoviral hemorrhagic cystitis (n=8) were significantly higher in patients with prednisolone dose >or=1 mg/kg at the time of diagnosis of cGVHD. The present results suggest that infections associated with cGVHD, especially after high-dose prednisolone, are predictive of poor outcome regardless of whether the patient received RIC or CIC.
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PMID:Infectious complications in chronic graft-versus-host disease: a retrospective study of 145 recipients of allogeneic hematopoietic stem cell transplantation with reduced- and conventional-intensity conditioning regimens. 1819 71

Chronic kidney disease (CKD) is common after hematopoietic cell transplantation (HCT). We prospectively measured the urinary albumin:creatinine ratio (ACR) in 142 patients. Total (intact) monomeric albumin was determined by liquid chromatography of untreated urine samples collected weekly to day 100 after HCT. Albuminuria was defined as ACR (mg/g creatinine) > 30; proteinuria, as ACR >300. Cox and logistic regression analyses evaluated ACR as a risk factor for clinical events. The prevalence of albuminuria was 37% at baseline, 64% at day 100, and 50% at 1 year. Proteinuria occurred in 4% of patients at baseline, in 15% at day 100, and in 4% at 1 year. Characteristics associated with albuminuria include age, sex, donor type, hypertension, and sinusoidal obstruction syndrome (SOS). Albuminuria was associated with an increased risk of acute graft-versus-host disease (aGVHD) and bacteremia, but not acute kidney injury (AKI). Albuminuria at day 100 was associated with CKD at 1 year (odds ratio = 4.0; 95% confidence interval [CI] = 1.1 to 14.6). Nonrelapse mortality (NRM) risk was elevated (hazard ratio = 6.8; 95% CI = 1.1 to 41.5) in patients with overt proteinuria at day 100. Albuminuria occurs frequently after HCT and is correlated with aGVHD, bacteremia, hypertension, and progression of renal disease. Proteinuria at day 100 is associated with an 6-fold increased risk of NRM by 1 year after HCT.
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PMID:Albuminuria in hematopoietic cell transplantation patients: prevalence, clinical associations, and impact on survival. 1904 Oct 58

We report on the incidence, risk factors, and outcome of late Staphylococcus aureus bacteremia (SAB) in a cohort of 709 adult and pediatric patients at Memorial Sloan-Kettering Cancer Center between September 1999 and December 2006. The SAB cases were identified by prospective surveillance and examination of a computerized database. Late SAB was defined as SAB occurring > 50 days post-hematopoietic stem cell transplantation (HSCT). A nested case-controlled study was conducted to identify predictors of late SAB. The incidence of late SAB was 6/100,000 patient-days. The median time from stem cell infusion to incident blood culture was 137 days (range, 55 to 581 days). Eighty-four percent of the cases were community acquired; 40% involved a focal infection. Bacteremia was persistent (>3 days) despite removal of endovascular access in > 50% of cases. Risk factors for late SAB were acute graft-versus-host disease (aGVHD) flare, acute or chronic skin GVHD (cGVHD), corticosteroid use, liver dysfunction, and prolonged hospital length of stay (LOS) post-HSCT. In multivariate models, skin GVHD (P = .002) and LOS (P = .02) remained significant. The median survival post-SAB was 135 days (range, 1 to 1765 days). Late SAB occurred mainly in the setting of GVHD or corticosteroid therapy. Clinical manifestations were highly variable. Multiple comorbidities, indicated by organ dysfunction and hospitalization, likely contributed to persistence and increased morbidity and mortality. We recommend a high index of suspicion and empiric antistaphylococcal treatment pending culture results in high-risk patients undergoing HSCT.
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PMID:Risk factors for late Staphylococcus aureus bacteremia after allogeneic hematopoietic stem cell transplantation: a single-institution, nested case-controlled study. 1904 Oct 67

Reductions in the duration and nadir of neutropenia have translated into a significant decrease in bacteremia in adult recipients of allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) during the first 30 days after transplantation. It remains to be determined whether RIC allo-SCT also will result in a decrease in systemic viral infections (SVIs) and invasive fungal infections (IFIs), which are more dependent on alterations in cellular immunity. We compared the incidence of SVIs and IFIs in children receiving busulfan-based RIC allo-SCT and in children receiving myeloablative conditioning (MAC) allo-SCT for various malignant and nonmalignant diseases. Allo-SCT recipients at risk for cytomegalovirus (CMV) received ganciclovir/foscarnet, and most of the patients received antifungal prophylaxis with liposomal amphotericin B until day +100. Eighty-six patients (median age, 7.5 years; 70% with malignant disease, 30% with nonmalignant disease; 80% average risk, 20% poor risk) were evaluated. The probability of developing grade II-IV acute graft-versus-host disease (aGVHD) was 29.1% (95% confidence interval [CI]=16.7%-41.6%) in RIC allo-SCT versus 40.3% (95% CI=23.9%-56.6%) in MAC allo-SCT (P=.23), and that of chronic GVHD (cGVHD) was 28.9% (95% CI=14.7%-43.0%) in RIC allo-SCT versus 28.4% (95% CI=10.5%-46.3%) in MAC allo-SCT (P=.73). The overall probability of developing an SVI was 58%, and that of developing an IFI was 15%. These probabilities did not differ significantly by conditioning intensity. In a multivariate Cox regression model, the following were identified as independent risk factors for invasive fungal infection: older age (hazard ratio [HR]=1.3; 95% CI=1.1-1.6; P=< .01), poor risk status (HR=6.5; 95% CI =1.1-37.4; P=.03), and CMV-positive recipient (high vs low CMV risk group, HR=26.7; 95% CI=3.4-210.8; P=< .01). Overall infection-related mortality was only 1.1% (1/86) for SVIs and 2.3% (2/86) for IFIs. Our data indicate that RIC allo-SCT does not carry a lower risk of SVIs and IFIs than MAC allo-SCT in pediatric recipients.
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PMID:Incidence of Viral and fungal infections following busulfan-based reduced-intensity versus myeloablative conditioning in pediatric allogeneic stem cell transplantation recipients. 1989 83

Patients aged 0-18 years with confirmed or possible invasive fungal infection were identified by medical record and database searches. Cases with an underlying diagnosis of acute leukaemia or following stem cell transplantation were included in a case control study. Controls included all other children with acute leukaemia or stem cell transplant in the corresponding time period. Variables collected included demographics, underlying disease risk and status, organ impairment, admission to intensive care unit, fungal infection details and certain transplant variables. Risk factors for development of invasive fungal infection were examined using logistic regression. There were 106 cases of invasive fungal infection during the study. The incidence of invasive fungal infection was 21% in acute lymphoblastic leukaemia, 15% in acute myeloid leukaemia and 25% following stem cell transplantation. Sixty per cent were neutropenic at diagnosis and 39% had concomitant bacteremia. High risk acute lymphoblastic leukaemia, relapsed disease, intensive care admission and graft-versus-host disease were significantly associated with development of invasive fungal infection on multivariate analysis. These associations provide new information on paediatric invasive fungal infections and warrant further study; caution should be encouraged when extrapolating from adult studies.
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PMID:Epidemiology of paediatric invasive fungal infections and a case-control study of risk factors in acute leukaemia or post stem cell transplant. 2009 13

The incidence of nontyphoidal Salmonella (NTS) infections is rising worldwide and several outbreaks have been reported recently. Immunosuppressed patients are particularly vulnerable to NTS infections. We retrospectively examined the clinical features and outcomes of 18 recipients of hematopoietic SCT (HSCT) who were diagnosed with NTS infection at our institution during a 15-year period. Bacteremia was the most common presenting feature and occurred in 67% of cases. Diarrhea was absent in one-third of cases. Among 12 recipients of allogeneic HSCT, 8 presented with bacteremia and only 6 had diarrhea. A total of 9 of these 12 patients had chronic GVHD. Metastatic disease was distinctly rare and occurred in only two patients, whereas one patient died of NTS sepsis. Food safety practices to prevent NTS infection are important in HSCT recipients, particularly for those who have chronic GVHD after allogeneic HSCT.
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PMID:Nontyphoidal Salmonella infection among recipients of hematopoietic SCT. 2083 89


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