Influenza a outbreak in an ambulatory stem cell transplant center.

BACKGROUND: In the era of cost-consciousness regarding healthcare , provision of medical services in an outpatient setting has become increasingly attractive. We report an influenza outbreak in an ambulatory stem cell transplant center in 2013 that highlights unique identification and infection control challenges in this setting. METHODS: Nasopharyngeal swabs were performed on patients with suspected influenza-like illnesses (ILI), defined by subjective fever or measured temperature of ≥37.7°C (≥100°F) with cough or sore throat during July 25, 2013 through August 7, 2013. In addition, testing was triggered by an elevated C-reactive protein (CRP). Specimens were analyzed by using eSensor Respiratory Viral Panel. Clinical and epidemiologic information was collected in real time, and frequencies were calculated on demographics, baseline clinical parameters, treatment methods, comorbidities, and symptoms of affected persons. RESULTS: Thirty-one patients had influenza A (H3N2) infection during July 25, 2013 through August 7, 2013. Only 7 patients (23%) met the Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists ILI case definition. Twenty-five patients (81%) had received ≥1 transplant, with 13 (42%) having occurred within 1 year before the outbreak. Twenty-five patients (81%) had received B-cell active chemotherapy <60 days before influenza diagnosis, 6 (19%) were neutropenic, and 25 (81%) lymphopenic. Among clinical and laboratory markers analyzed, abnormal CRP was the most sensitive screening tool for influenza. Twelve (39%) patients were hospitalized (median stay, 10 days; range, 2-20). No deaths occurred. CONCLUSIONS: Immunocompromised hosts with influenza have atypical presentations. Existing surveillance case definitions might be insufficient to reliably identify influenza outbreaks in such patients.

Baseline platelet count and creatinine clearance rate predict the outcome of neutropenia-related invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) is a life-threatening infection for immunocompromised patients. Improvement in IA outcome has been hampered by lack of early prognostic factors, namely, those available before starting chemotherapy (baseline) or early in the course of IA (nonbaseline). We hypothesized that prognostic factors can be identified before chemotherapy, ≤7 days from the first positive serum Aspergillus galactomannan index (s-GMI). METHODS: We analyzed 98 patients with multiple myeloma who developed neutropenia-related IA and had a positive s-GMI. Three response criteria were used: kinetics of s-GMI, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions, and 6-week survival. Baseline and nonbaseline variables were analyzed separately. RESULTS: Independent response predictors at baseline were a platelet count ≥65,000 platelets/mm(3) (odds ratio [OR], 1.009; 95% confidence interval [CI], 1.001-1.017; P = .03) by s-GMI kinetics, and a platelet count ≥65,000 platelets/mm(3) (OR, 1.009; 95% CI, 1.002-1.017; P = .01) and a creatinine clearance rate ≥53 mL/min (OR, 1.024; 95% CI, 1.006-1.042; P = .009) by EORTC/MSG criteria, with response rates of 83% and 28% when both variables were above or below these cutoffs, respectively (P < .001). Only baseline creatinine clearance rate ≥53 mL/min predicted 6-week survival (P = .003). Normalization of the s-GMI ≤7 days after the first positive s-GMI and neutrophil recovery were the nonbaseline factors associated with positive outcomes. CONCLUSIONS: Two simple, inexpensive to measure, widely available, and routinely collected prechemotherapy values, platelet count and creatinine clearance rate, predict IA outcome and stratify patients into low-, intermediate-, and high-risk categories, while early evaluation of s-GMI allows timely treatment modification. These findings may improve patient outcomes by optimizing management strategies for this serious infection and may prove valuable in designing clinical trials of interventions to improve IA outcomes.

Earlier response assessment in invasive aspergillosis based on the kinetics of serum Aspergillus galactomannan: proposal for a new definition.

BACKGROUND: Current criteria for assessing treatment response of invasive aspergillosis (IA) rely on nonspecific subjective parameters. We hypothesized that an Aspergillus-specific response definition based on the kinetics of serum Aspergillus galactomannan index (GMI) would provide earlier and more objective response assessment. METHODS: We compared the 6-week European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) response criteria with GMI-based response among 115 cancer patients with IA. Success according to GMI required survival with repeatedly negative GMI for ≥2 weeks. Time to response and agreement between the 2 definitions were the study endpoints. RESULTS: Success according to EORTC/MSG and GMI criteria was observed in 73 patients (63%) and 83 patients (72%), respectively. The GMI-based response was determined at a median of 21 days after treatment initiation (range, 15-41 days), 3 weeks before the EORTC/MSG time point, in 72 (87%) of 83 responders. Agreement between definitions was shown in all 32 nonresponders and in 73 of the 83 responders (91% overall), with an excellent κ correlation coefficient of 0.819. Among 10 patients with discordant response (EORTC/MSG failure, GMI success), 1 is alive without IA 3 years after diagnosis; for the other, aspergillosis could not be detected at autopsy. The presence of other life-threatening complications in the remaining 8 patients indicates that IA had resolved. CONCLUSIONS: The Aspergillus-specific GMI-based criteria compare favorably to current response definitions for IA and significantly shorten time to response assessment. These criteria rely on a simple, reproducible, objective, and Aspergillus-specific test and should serve as the primary endpoint in trials of IA.

A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients.

We prospectively evaluated the bone changes associated with proteasome inhibition using single agent bortezomib in relapsed or refractory myeloma patients. Ten patients received bortezomib 1.3 mg/m(2) per days 1, 4, 8 and 11 for three 21-day cycles, and 6 patients received 1 mg/m(2) per day with the same schedule. Bone architecture and metabolism changes were assessed by bone markers, micro-CT, bone histomorphometry, tetracycline labeling and serum parathormone levels. Bone parameter variations were compared by response to treatment. Microarchitectural changes were observed in all evaluable responsive patients. Bone alkaline phosphatase changes were associated with disease response (≥PR vs. others P=0.03 cycle 1, day 11) serum parathormone levels were also significantly increased (P=0.04 on days 11, 21, 33) in responding individuals. This study demonstrates that the myeloma control produced by proteasome inhibition is associated with bone changes and to a discrete pattern of hormonal variation.

Probable invasive aspergillosis without prespecified radiologic findings: proposal for inclusion of a new category of aspergillosis and implications for studying novel therapies.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) definition of invasive aspergillosis used in clinical trials lacks sensitivity. We hypothesize that giving lower weight to the prespecified radiologic findings in patients with a positive serum galactomannan index test result will improve the definition's diagnostic sensitivity. METHODS: The medical records of 121 patients with 125 cases of invasive aspergillosis treated at a referral cancer institute from January 2003 through December 2009 were reviewed. Aspergillosis was diagnosed as EORTC-MSG proven or probable (controls, 83) or probable invasive aspergillosis without prespecified radiologic criteria (cases, 42). The latter differed from the former by the inclusion of patients whose pulmonary infiltrates, although well described in invasive aspergillosis, do not fulfill EORTC-MSG invasive aspergillosis requirements. The host, clinical, and mycologic characteristics and survival of cases and controls served as end points. RESULTS: A total of 114 (91%) of 125 patients had multiple myeloma. Patients had a median age was 65 years (range, 26-81 years), and 74 were male. All had received antineoplastic therapy, including stem cell transplantation (58 [46%]). Aspergillosis involved lungs (88 patients), sinuses (9 patients), or both (28 patients). Except for higher median baseline platelet count and shorter duration of neutropenia among cases, there were no statistically significant differences between groups on all predefined end points, including 4-, 6-, and 12-week survival. Eleven of 26 cases were reclassified as controls on the basis of subsequent imaging. CONCLUSIONS: Except for less well-circumscribed consolidations, the host, clinical, radiologic, and mycologic characteristics and outcome of patients with probable invasive aspergillosis but without prespecified radiologic criteria are similar to those with EORTC-MSG invasive aspergillosis. Enrolling such patients in clinical trials of novel therapies will increase the pool of eligible study participants and improve trial speed and efficiency.