The use of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis is associated with increased rates of organ-specific toxicities. Despite limited data, the European Society for Blood ...and Marrow Transplantation-European LeukemiaNet working group recommend the use of folinic acid (FA) rescue to reduce MTX toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). In a multicenter, double-blind, randomized, controlled trial, we explored whether FA rescue reduces MTX-induced toxicity. We enrolled patients undergoing allo-HCT with myeloablative conditioning with peripheral blood stem cell grafts, with GVHD prophylaxis consisting of cyclosporine and MTX. Patients were randomized to receive FA or placebo starting 24 hours after each MTX dose and continuing over 24 hours in 3 to 4 divided doses. The primary end point was the rate of grades 3 and 4 oral mucositis. After enrollment of 52 patients (FA, n = 28; placebo, n = 24), preplanned interim analysis revealed similar rates of grade 3 and 4 (46.6% vs 45.8%;P= .97) and grades 1 to 4 (83.3% vs 77.8%;P= .65) oral mucositis. With a median follow-up of 17 (range, 4.5-50) months, there was no difference in the rates of acute and chronic GVHD, disease relapse, nonrelapse mortality, and overall survival. These interim results did not support continuation of the study. We conclude that FA rescue after MTX GVHD prophylaxis does not decrease regimen-related toxicity or affect transplantation outcomes. This study was registered atclinicaltrials.govas #NCT02506231.
•FA rescue following MTX GVHD prophylaxis does not decrease regimen-related toxicity or affect transplantation outcomes.
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Background Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia, often as a result of ventilator equipment contamination. Evidence-based guidance on optimal care of ...ventilator equipment to prevent infection is lacking. Here, we report on a significant and persistent reduction in A baumannii infection rates achieved by introducing a strict policy on ventilator care. Methods We implemented an institution-wide ventilator care policy that included routine exchange of breathing circuits and external bacterial filters (every 7-14 days) and replacement followed by routine sterilization of internal bacterial filters (every 4-8 weeks). We analyzed sputum cultures and patient outcomes among ventilated patients before and after the intervention. Results Between January 2012 and March 2013, 321 patients ventilated for more than 3 days comprised the study cohort. Health care-associated A baumannii acquisition was significantly reduced during the postintervention period (33% vs 16%; odds ratio, 0.39; 95% confidence interval, 0.23-0.67; P = .0008). Additionally, the median time to A baumannii acquisition was significantly longer postintervention (59 vs 21 days; P < .0001). A baumannii ventilator-associated pneumonia risk was also reduced postintervention (odds ratio, 0.39; P = .005). Conclusions Implementing a stricter standard of ventilator care than that currently defined in published guidelines can significantly decrease health care-associated A baumannii acquisition and related adverse outcomes among ventilated patients.
Abstract
Acute graft-versus-host disease (GVHD) has compromised and continues to compromise the benefits associated with allogeneic hematopoietic cell transplant to cure malignant and non-malignant ...diseases. Pharmacologic interventions to prevent GVHD have emerged as a major objective of research in the immunology and transplant fields. A better understanding of the pathobiology behind the GVHD process has led the way to novel approaches and medications. Here we review the present arsenal of medications used to prevent GVHD, focusing on past experience and the current evidence, and discuss future potential targets.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background. Prediction of bloodstream infection at the time of sepsis onset allows one to make appropriate and economical management decisions. Methods. The TREAT computerized decision-support system ...uses a causal probabilistic network, which is locally calibrated, to predict cases of bacteremia. We assessed the system's performance in 2 independent cohorts that included patients with suspected sepsis. Both studies were conducted in Israel, Italy, and Germany. Data were collected prospectively and were entered into the TREAT system at the time that blood samples were obtained for culture. Discriminative power was assessed using a receiver-operating characteristics curve. Results. In the first cohort, 790 patients were included. The area under the receiver-operating characteristics curve for prediction of bacteremia using the TREAT system was 0.68 (95% confidence interval CI, 0.63–0.73). We used TREAT's prediction values to draw thresholds defining a low-, intermediate-, and high-risk groups for bacteremia, in which 3 (2.4%) of 123, 62 (12.8%) of 483, and 55 (29.9%) of 184 patients were bacteremic, respectively. In the second cohort, 1724 patients were included. The area under the receiver-operating characteristics curve was 0.70 (95% CI, 0.67–0.73). The prevalence of bacteremia observed in the low-, intermediate-, and high-risk groups defined by the first cohort were 1.3% (4 of 300 patients), 13.2% (150 of 1139 patients), and 28.1% (80 of 285 patients), respectively. The low-risk groups in the 2 cohorts comprised 15%–17% of all patients. Performance was stable in the 3 sites. Conclusions. Using variables available at the time that blood cultures were performed, the TREAT system successfully stratified patients on the basis of the risk for bacteremia. The system's predictions were stable in 3 locations. The TREAT system can define a low-risk group of inpatients with suspected sepsis for whom blood cultures may not be needed.
Patients with acute myeloid leukemia (AML) who progress after exposure to hypomethylating agents (HMA) have a dismal prognosis. We hypothesized that the addition of venetoclax, a BCL-2 inhibitor, to ...AML patients who previously failed HMA might overcome resistance. Adult patients (≥ 18 years) with AML were eligible if leukemia relapsed after, or was refractory to HMA. In general, in addition to venetoclax, patients continued HMA or other low-intensity therapies. Patients who previously underwent allogeneic hematopoietic cell transplantation (HCT) were also eligible. Data were analyzed in November 2018. Twenty-three patients were treated between October 2016 and October 2018 and were eligible for this study. Median age was 76 years and 6 patients had leukemia that relapsed post allogeneic HCT. None of the patients experienced tumor lysis syndrome and toxicities were as expected and manageable. Febrile neutropenia was the most common toxicity (78% of patients). Median hospitalization time was 13 days. Forty-three percent of the patients achieved CR/CRi. Overall survival (OS) was 74% at 6 months and median OS in patients who achieved remission was 10.8 months. Higher number of blasts in both bone marrow and peripheral blood was associated with lower chances of CR, while higher WBC, LDH, and bone marrow or peripheral blasts were associated with increased mortality rate. The addition of venetoclax to patients with HMA-refractory AML may result in a substantial anti-leukemic activity, specifically in those achieving complete remission. This should be further tested in a well-designed prospective trial.
Extended infusion of β-lactam antibiotics in patients with febrile neutropenia resulted in a higher rate of clinical success compared with standard bolus infusion. The benefit of extended β-lactam ...infusion was greatest among patients with pneumonia.
Abstract
Background
Febrile neutropenia may be a sign of severe infection and is associated with significant morbidity and mortality in high-risk patients with hematologic malignancies. Extended infusion of β-lactam antibiotics is associated with greater clinical response than is bolus infusion in nonneutropenic critically ill patients, but data are lacking for febrile neutropenic patients.
Methods
We designed a single-center, nonblinded, randomized trial to compare extended infusion (4 hours) and bolus infusion (30 minutes) of piperacillin-tazobactam or ceftazidime in high-risk patients with febrile neutropenia. The primary endpoint was overall response on day 4, defined as the combination of resolution of fever, sterile blood cultures, resolution of clinical signs and symptoms, and no need for a change in the antibiotic regimen. Outcome was adjudicated by investigators blinded to treatment allocation.
Results
Of 123 enrolled patients, 105 had febrile neutropenia and were included in the intention-to-treat analysis: 47 in the extended infusion arm and 58 in the bolus infusion arm. Overall response occurred in 35 (74.4%) patients treated with extended infusion and 32 (55.1%) patients treated with bolus infusion (P = .044). The superiority of extended infusion was greatest for patients with clinically documented infections (overall response, 68.4% 13/19 vs 35.7% 10/28; P = .039) and specifically for those with pneumonia (80% 4/5 vs 0% 0/8; P = .007).
Conclusions
Extended infusion of β-lactams is associated with superior treatment outcomes compared with bolus infusion for high-risk patients with febrile neutropenia. The benefit of extended β-lactam infusion may be greatest for patients with pulmonary infections.
Clinical Trials Registration
NCT02463747.
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