Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation

A cohort of 138 children with 144 hematopoietic stem cell transplantation (HSCT) performed in 1997-2006 were analyzed to evaluate risk factors and mortality predictors of hepatic veno-occlusive disease (VOD). Nineteen patients (13.2%) developed VOD (nine boys, median age 3.5 years) at 1-21 days after HSCT (median 13 days). Age < or =2 years at transplant (odds ratio (OR)=5.25, P=0.011), BU-CY conditioning (OR=5.16, P=0.001), thalassemia major (OR=3.97, P=0.015), platelet engraftment beyond day +21 (OR=8.67, P=0.025) were univariate risk factors for VOD. The first two remained significant in multivariate regression. Seven patients (36.8%) with VOD died, at a median of 44 days post transplant (range, 30-421 days). The 5-year survival was 62%. All surviving patients had normal liver function on follow-up at 0.5-9 years. Patients with VOD had higher 100-day mortality (16.3 vs 9.6%, P=0.024). Mortality predictors included donors other than autologous or matched sibling (hazard ratio (HR)=23.6, P=0.006), hepatic and cutaneous GVHD (HR=8.15, P=0.038), maximal weight gain >9% (HR=6.81, P=0.023), pleural effusion, intensive care unit admission, peak bilirubin >300 micromol l(-1) (HR=13.6, P=0.016), day +21 bilirubin >200 micromol l(-1) (HR=33.9, P=0.001), and rise of bilirubin >15 micromol l(-1) per day within the first week (HR=19.8, P=0.006). Mortality was substantially higher if >3 predictors were present (HR=33.9, P=0.001). Meticulous monitoring in high-risk patients and early treatment should be considered before VOD progresses beyond salvage.     

造血干细胞移植后患者侵袭性真菌感染发生及危险因素分析

目的 了解造血干细胞移植（HSCT）后患者侵袭性真菌感染（ZVI）的发病率及危险因素。方法 选择2003年6月至2004年9月于我所进行HSCT的患者148例,按照我国IFI的诊断标准及临床疗效进行回顾性分析。结果 诊断IFI的患者共52例,其中确诊者35例,拟诊者17例。其发生时间为移植后2—400d,中位时间为62d。确诊IFI在移植后3、6个月及1年的累积发病率分别为15．6％、42．5％、48．9％。根据多因素分析,早期IFI的危险因素为：Ⅲ～Ⅳ度的急性移植物抗宿主病（GVHD）、广谱抗生素的长期应用及巨细胞病毒感染;晚期IFI的危险因素为：广泛型慢性GVHD和激素的长期应用。结论 具有较多危险因素的HSCT受者更易发生IFI,而避免或减少上述危险因素是预防IFI的有效方法。     

Incidence and outcomes of Clostridium difficile-associated disease in hematopoietic cell transplant recipients

Hematopoietic stem cell transplant (HSCT) recipients are at a high risk of Clostridium difficile-associated disease (CDAD) given frequent hospitalizations, prolonged antibiotic usage and altered integrity of intestinal mucosa. The prevalence and trends of CDAD in HSCT patients have not been extensively studied. In this study, the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify CDAD in HSCT patients using a nationwide inpatient sample in the United States from 2000 to 2009. The prevalence of CDAD and in-hospital mortality in HSCT were investigated and compared to those without any transplants. Multivariate analysis was performed to identify if BMT and graft versus host disease (GVHD) were independently associated with mortality in CDAD patients. Of the 344,507 HSCT discharges, 4.7 % had CDAD. This was about 5 times higher when compared to non-transplant discharges. During engraftment admission, rates of CDAD were higher in allogenic group (8.4 vs. 5.7 %, p < 0.001). In subsequent admissions, those with GVHD had higher rates of CDAD (5.7 vs. 3.2 %, p < 0.001). On adjusted analysis in patients with CDAD, during engraftment admission, allogenic group had significantly higher mortality when compared with non-transplants (OR 3.7). Notably, there was no significant difference in mortality between patients with and without CDAD during the engraftment period for the allogeneic group. In subsequent admissions, there was higher mortality in those with GVHD (OR 4.8). Though the prevalence of CDAD in non-transplant population doubled (from 0.44 % in 2000 to 0.99 % in 2008), it has remained stable in HSCT patients (from 4.8 % in 2000 to 5.6 % in 2008). HSCT and GVHD are independently associated with CDAD though its presence does not affect mortality.     

Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients

M. Mikulska, V. Del Bono, R. Prinapori, L. Boni, A.M. Raiola, F. Gualandi, M.T. Van Lint, A. Dominietto, T. Lamparelli, P. Cappellano, A. Bacigalupo, C. Viscoli. Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.
Transpl Infect Dis 2010: 12: 505–512. All rights reserved Abstract: Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case–control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2–24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65–48.99 and OR=7.52, 95% CI, 1.56–36.31, respectively, P=0.047); severe (grades 3–4) mucositis (OR=9.04, 95% CI, 1.97–41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11–18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93–18.66 for 1–7 days of therapy, and OR=7.31, 95% CI, 1.78–30.12 for 8–23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06–0.97, P=0.045 and OR=0.11, 95% CI, 0.02–0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.     

Incidence and outcome of idiopathic pneumonia syndrome in pediatric stem cell transplant recipients

Idiopathic pneumonia syndrome (IPS) is a rare complication following stem cell transplant (SCT) and its incidence among pediatric SCT recipients is not known. To assess the incidence of IPS, we retrospectively reviewed the incidence of IPS at our center. IPS is defined as the presence of multilobar infiltrates by chest radiograph or computed tomography scan, need for supplemental oxygenation with declining pulse oximetry and no identifiable pulmonary infection. Between July 1999 and August 2005, 11 of 93 children who received a fully ablative allogeneic SCT (11.8%) developed IPS. All 11 patients had normal pulmonary evaluation before transplant. IPS developed at a median of 17 days (range 8-42 days) after transplant. Recipients of unrelated donor transplant had increased risk of developing IPS. There was a significant association between acute or hyperacute graft-versus-host disease (GVHD) and IPS (P=0.035). All patients had significant hypoxia and five patients required assisted ventilation. IPS was the cause of death in two patients. Although there was complete resolution of respiratory symptoms in the other nine patients, overall transplant-related mortality was significantly higher among patients with IPS (64 vs 17%, P=0.002). IPS is a relatively common complication in pediatric SCT recipients and acute GVHD is an important associated factor.     

Experience from a single paediatric transplant centre with identification of some protective and risk factors concerning the development of hepatic veno-occlusive disease in children after allogeneic hematopoietic stem cell transplant

Hepatic veno-occlusive disease (VOD) is a frequent and severe complication of hematopoietic stem cell transplantation (HSCT) affecting 9.6–17.3 % of cases. 200 HSCT, performed between January 1995 and March 2013 in our Paediatric HSCT Centre in Trieste, were retrospectively analysed to evaluate the frequency of VOD and to identify the associated risk factors. The frequency of VOD according to the Seattle criteria was 17 %, within the range reported in literature. The mortality rate was 37.5 % (75 out of 200 transplantations) in the general population and 73.5 % (25 out of 34) in VOD patients (p < 0.05). Veno-occlusive disease significantly decreased from 38 % (1995–2000) to 8 % (2007–2013) p < 0.05. Univariate and multivariate analyses identified sepsis and pre-transplant ferritin levels above 1000 ng/ml as two significant risk factors for VOD, while the use of tacrolimus appeared to be associated with a lower VOD risk. Veno-occlusive disease still remains an important cause of transplant-related mortality even if it appears to have decreased over the last few years.     

Aspergillosis in hematopoietic stem cell transplant recipients: Risk factors, prophylaxis, and treatment

This article discusses newer antifungal agents, recent randomized controlled trials, and the 2008 guidelines for treatment of aspergillosis in reference to hematopoietic stem cell transplantation (HSCT). Strategies such as reduced-intensity conditioning and agents such as infliximab shed new light on aspergillosis risk. The association between Toll-like receptor polymorphisms and aspergillosis is an exciting development. Posaconazole was evaluated in two randomized prophylaxis trials, and a large, randomized trial established voriconazole’s therapeutic superiority to amphotericin. However, many questions remain regarding which patients benefit most from prophylaxis; resistance to newer antifungals; and combination, salvage, and immunomodulatory therapies. Current therapies and strategies have improved the outlook of HSCT recipients with invasive aspergillosis. Future directions include increasingly sophisticated risk stratification, clinical testing of combination therapies, and adjunctive immunomodulatory therapies.     

Antifungal prophylaxis in hematopoietic stem cell transplant recipients

Infections remain a major complication of hematopoietic stem cell transplantation, with recent trends indicating that fungal pathogens have become one of the most common causes of death. Attention has turned to the use of prophylactic antifungal medications to prevent infection with both Candida and Aspergillus species. Recent studies, which are reviewed within, indicate success in preventing infections caused by azole-susceptible Candida species, accompanied by improved transplant-related mortality rates in high-risk patients. Further studies are necessary to develop strategies to prevent infection with Aspergillus species.     

Hepatic veno-occlusive disease following hematopoietic stem cell transplantation

The clinical syndrome of hepatic veno-occlusive disease (VOD) is one of the most common and serious complications following hematopoietic stem cell transplantation (SCT). High-dose chemotherapy or chemoradiation therapy in the context of autologous and allogeneic SCT can profoundly injure sinusoidal endothelium and hepatocytes within zone 3 of the liver acinus, producing the clinical syndrome of hepatomegaly and/or right upper quadrant pain with jaundice and fluid retention, typically manifest as weight gain. The incidence is variable and ranges from 10 to 60%. Mild to moderate disease is characterized by eventual complete resolution. In contrast, severe disease frequently results in multiorgan failure and death. The purpose of this review is to discuss the pathophysiology and clinical features of VOD, and the current status and future directions of research for both prevention and treatment.     

Adenovirus infections in hematopoietic stem cell transplant recipients.

We report a 12% incidence of adenovirus infections among 532 recipients of hematopoietic stem cell transplant (HSCT) from January 1986 through March 1997. The median time from day of stem cell infusion to first positive culture was 41 days. Recipients of allogeneic stem cells, as opposed to autologous stem cell recipients, were more likely to have a culture positive for adenovirus (16% vs. 3%; P<.0001). Pediatric patients were also more likely than adults to have a positive culture (23% vs. 9%; P<.0001). Among stem cell recipients with partially matched related donors, pediatric recipients appear to be at significantly greater risk for infection than adult recipients (P<.001). Positive cultures were associated with evidence of invasion in 64% of cases (41 of 64). A multiple logistic regression analysis showed that isolating adenovirus from more than 1 site correlated with greater risk for invasive infections (P=.002). Invasive infections were associated with poorer chance of survival.     

Infection surveillance in pediatric hematopoietic stem cell transplantation recipients

Objective

To describe the profile of reported healthcare‐associated infections (HAIs) in pediatric patients submitted to hematopoietic stem cell transplantation (HSCT) at a reference center.

Methods

Retrospective cohort of pediatric patients who were submitted to HSCT from 2008 to 2016. The criteria for HAI were based on those established by the National Healthcare Safety Network. Data were collected by active surveillance performed daily by professionals. This study was approved by the institutional research ethics committee.

Results

A total of 86 HSCTs were performed in 81 patients younger than 18 years of age (median, 10 years). Of these, 69 (85%) were males. Aplastic anemia and leukemia were the main diagnoses. A total of 140 HAIs were diagnosed with an incidence density of 28.2 infections/1000 patient‐days. The most common HAI was laboratory‐confirmed bloodstream infection (46), the majority of which was reported to be central venous catheter‐associated (43). Gram‐negative bacteria were the most prevalent microorganisms (58.5%). Almost all the infections occurred until 30 days after transplantation, and 17 deaths were observed within 180 days after the procedure.

Conclusion

Active surveillance of HAIs in HSCT children allowed the evaluation of the incidence and profile of HAIs, which is essential for the health care of these patients.