Yield of repeat blood cultures in acute myeloid leukemia patients with febrile neutropenia and bacteremia following allogeneic hematopoietic stem cell transplant.

INTRODUCTION: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. RESULTS: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. CONCLUSION: Among bacteremic AML patients in the post-HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low.

Serum interleukin-33 and soluble suppression of tumorigenicity 2 in pediatric leukemia with febrile neutropenia.

The purpose of this study was to evaluate the association between interleukin-33 (IL-33) and its receptor Soluble Suppression of Tumorigenicity-2 (sST2) levels and bacterial infections during febrile neutropenia (FN) in pediatric patients with acute lymphoblastic leukemia (ALL). In this prospective, case-control study, participants were divided into 3 groups: ALL patients with FN (Group A), ALL patients without neutropenia and fever (Group B), and healthy children without infection and chronic disease (Group C). There were 30 cases in each group. Blood samples for IL-33 and sST2 have been drawn from patients in Group A before the initiation of treatment and on days 1 and 5 of treatment, and from patients in Groups B and C at initiation. At admission, mean IL-33 level (39.02 ± 26.40 ng/L) in Group B and mean sST2 level (185.3 ± 371.49 ng/ml) in Group A were significantly higher than the other groups (p = 0.038, p < 0.001, respectively). No difference was observed in the mean IL-33 and sST2 levels in the 5-day follow-up of patients in Group A (p = 0.82, p = 0.86, respectively). IL-33 and sST2 levels were not associated with fever duration, neutropenia duration or length of hospitalization. While C-reactive protein (CRP) was significantly higher in patients with positive blood culture (p = 0.021), IL-33 (p = 0.49) and sST2 (p = 0.21) levels were not associated with culture positivity.  Conclusion: IL-33 and sST2 levels were not found valuable as diagnostic and prognostic markers to predict bacterial sepsis in patients with FN. What is Known: • Neutropenic patients are at high risk of serious bacterial and viral infections, but the admission symptom is often only fever. • Febrile neutropenia has a high mortality rate if not treated effectively. What is New: • Febrile neutropenia is not only caused by bacterial infections. Therefore, new biomarkers should be identified to prevent overuse of antibiotics. • Specific biomarkers are needed to diagnose bacterial sepsis in the early phase of febrile neutropenia.

Performance of serum procalcitonin as a biochemical predictor of death in hematology patients with febrile neutropenia.

INTRODUCTION: Historically, the measurement of serum procalcitonin (PCT) levels in patients with leukopenia has been rejected without sufficient prospective evidence to justify this argument. On the other hand, the accumulated use of broad spectrum antibiotics in these patients and their consequences make the use of PCT attractive in an effort to reduce its use. PATIENTS AND METHODS: We conducted a prospective study between 2016 and 2018, recruiting newly diagnosed FN patients, evaluating them with PCT levels during the first 24 h. After this we evaluate them with overall survival throughout the follow-up. RESULTS: A total of 81 episodes of FN in 72 patients were included. We report a mortality of 27.2% in our cohort. The mean serum PCT in these patients was 4.01 ng/mL compared to 0.42 ng/mL in the survivors group (p < 0.01). Using ROC curves, we determined a cut-off point to predict septic shock/death at 0.46 ng/mL. Patients with a procalcitonin >0.46 ng/mL had an increased risk of death, with a HR of 4.43, (p = 0.048). CONCLUSION: In conclusion, in our trial a single PCT on admission at a cut-off value of 0.46 ng/mL was able to predict the occurrence of septic shock and death in FN patients.

Cytokine and chemokine profiles in episodes of persistent high-risk febrile neutropenia in children with cancer.

BACKGROUND: In children with cancer and persistent high-risk febrile neutropenia (HRFN), cytokines/chemokines profiles can guide the differentiation of febrile neutropenia (FN) due to infections and episodes of unknown origin (FN-UO). METHODS: A prospective, multicenter study in Santiago, Chile included patients ≤ 18 years with cancer and HRFN. Clinical and microbiological studies were performed according to validated protocols. Serum levels of 38 cytokines/chemokines were determined on day 4 of persistent HRFN. We performed comparisons between i) HRFN episodes with a detected etiological agent (FN-DEA) and FN-UO, and ii) bacterial versus viral infections. ROC curves were used to assess the discriminatory power of the analytes. RESULTS: 110 HRFN episodes were enrolled (median age 8 years, 53% female). Eighty-four patients were FN-DEA: 44 bacterial, 32 viral, and 8 fungal infections. Twenty-six cases were categorized as FN-UO. Both groups presented similar clinical and laboratory characteristics. Nineteen out of 38 analytes had higher concentrations in the FN-DEA versus FN-UO group. G-CSF, IL-6, and Flt-3L showed the highest discriminatory power to detect infection (AUC 0.763, 0.741, 0.701). Serum levels of G-CSF differentiated bacterial infections and IP-10 viral agents. A combination of G-CSF, IL-6, Flt-3L, and IP-10 showed an AUC of 0.839, 75% sensitivity, and 81% specificity. CONCLUSION: A specific immune response is present on day four of persistent HRFN in children with cancer. We propose a combined measure of serum concentrations of G-CSF, IL-6, IP-10, and Flt-3L, in order to predict the presence of an infectious agent as compared to an episode of FN with unknown origin.

The use of serum endothelial adhesion molecules in pediatric patients with leukemia with febrile neutropenia to predict bacteremia.

OBJECTIVE: Febrile neutropenia (FN) represents a life-threatening complication in hematological malignancies. We aimed to analyze the utility of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF) levels compared with C-reactive protein (CRP) and procalcitonin (PCT) during febrile neutropenia episodes of pediatric patients with leukemia. METHODS: Two plasma samples, on day 0 (initial of episode) and day 3 (48-72 h after episode), for VCAM-1, ICAM-1 and VEGF, CRP and PCT were prospectively collected concomitantly during each febrile neutropenic episode between December 2016 and December 2017. The primary outcome was bacteremia and the secondary outcome was intensive care unit (ICU) admission. RESULTS: Twenty-two (28.6%) acute lymphoblastic lymphoma (ALL), seventeen (22.1%) acute myeloblastic lymphoma (AML) patients and thirty-eight (49.3%) control patients with no known underlying disease or fever were included in this study. Of the 39 patients; 16 (41%) had bacteremia. Mean serum sVCAM1 and sICAM1 levels were significantly higher in control group, compared to FN patients (p < 0.001). Mean serum sVCAM2 level was significantly higher in FN patients with bacteremia compared to FN patients without bacteremia (144.97 ± 70.35 pg/mL vs 85.45 ± 53.76 pg/mL, p = 0.022). Mean sVCAM1 and 2 levels were higher in FN patients with ICU admission. In this study, we found that sVCAM-1 and VEGF, when combined to CRP and PCT, could predict gram-negative bacteremia in FN episodes of pediatric hematological malignancy. CONCLUSION: Serum endothelial adhesion molecules, excluding sVCAM-1, cannot predict bacteremia and ICU admission alone in FN patients; but may be associated with clinical outcome when used with PCT and CRP.

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Treatment of myeloid malignancies relapsing after allogeneic hematopoietic stem cell transplantation with venetoclax and hypomethylating agents-a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group.

Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination of venetoclax and hypomethylating agents (HMAClax) for the treatment of relapse of myeloid malignancies after alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine (n = 13) or decitabine (n = 19); 11 patients received DLI in addition. HMAClax was the first salvage therapy in 8 patients. The median number of cycles per patient was 2 (1-19). All but 1 patient had grade 3/4 neutropenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%); 5 of these were fatal. In 30 evaluable patients, overall response rate (ORR) was 47% (14/30, 3 CR MRDneg, 5 CR, 2 CRi, 1 MLFS, 3 PR). ORR was 86% in first salvage patients versus 35% in later salvage patients (p = 0.03). In 6 patients with molecular relapse (MR), ORR was 67% versus 42% in patients with hematological relapse (HR) (n = 24, p = n.s.). After a median follow-up of 8.4 months, 25 patients (78%) had died and 7 were alive. Estimated median overall survival was 3.7 months. Median survival of patients with HMAClax for first versus later salvage therapy was 5.7 and 3.4 months (p = n.s.) and for patients with MR (not reached) compared to HR (3.4 months, p = 0.024). This retrospective case series shows that venetoclax is utilized in various different combinations, schedules, and doses. Toxicity is substantial and patients who receive venetoclax/HMA combinations for MR or as first salvage therapy derive the greatest benefit.

Optimized blood culture strategy to document febrile neutropenia.

BACKGROUND: Poor and delayed microbiological documentation of episodes of febrile neutropenia (EFN) deserves improvement. We assessed the impact of a new blood culture (BC) sampling protocol to optimize the diagnosis of bloodstream infection during EFN, compared with standard of care protocol. METHODS: This pre/post intervention included patients who presented an EFN in a pediatric hematology-oncology center. Data were compared between 1-year periods P1 (110 EFN, 53 patients) and P2 (124 EFN, 53 patients). Pre-intervention settings were 1-2 mL of blood cultured per BC set and several samplings over days (multisampling strategy) during period P1 vs. one unique early sampling of a large volume of blood (0.5-60 mL) depending on patient weight during period P2 (single-sampling weight-adapted strategy). Microbial detection and time-to-diagnosis were evaluated. RESULTS: Seventeen EFNs were microbiologically documented in P1 (15.5%) and 26 in P2 (21%). The rate of positive BC sets increased during P2 (10.4% vs. 5.8%). All cases of bacteremia were documented by BC drawn during the first 4 days of fever, and during P2 by samples obtained on the first day of fever. CONCLUSIONS: Bacteremia detection was improved. This proof-of-concept study shows benefits of combining the single-sampling strategy with large weight-adapted blood sampling strategy during EFN. IMPACT: Combination of single-sampling and weight-adapted blood culture strategies showed benefits in the documentation of bloodstream infections during febrile neutropenia. Bacteremia detection was improved in this preliminary study and this warrants further evaluation in the overall pediatric population. We observed no adverse effects associated with the new strategy while overall blood sparing was improved and handling of intravascular devices was reduced. The good tolerance of the blood sampling suggests that the recommended 1% volume limitation in children could be reconsidered. A similar evaluation is justified in the overall pediatric population suspected for bloodstream infection.

Predictive Value of FMO3 Variants on Plasma Disposition and Adverse Reactions of Oral Voriconazole in Febrile Neutropenia.

BACKGROUND AND OBJECTIVES: With the increasing number of patients with febrile neutropenia (FN), voriconazole (VRC) has been widely used in hospitals for first-line treatment of FN. The study was designed for evaluating the influence of FMO3 mutation on the plasma disposition and adverse reactions of VRC in FN. MATERIALS AND METHODS: A single-center observational study was conducted in the inpatient ward for 4 years. The genotypes of FMO3 and cytochrome P450 (CYP) 2C19 were detected by PCR-restriction fragment length polymorphism. Patients with neutropenia were screened according to the CYP2C19 metabolic phenotype and other inclusion criteria. Five days after empirical administration of VRC, blood concentrations of VRC and nitrogen oxides in patients' blood were determined by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI MS/MS). Serum parameters and clinical adverse reaction symptoms in the medical records were collected and statistically analyzed. RESULTS: A total of 165 patients with neutropenia with the intermediate metabolic phenotype of CYP2C19 were screened. At the initial stage of oral VRC treatment, patients with the FMO3 E308G genotype had a poorer plasma disposal ability to VRC than those with the wide type of FMO3 (WT) genotype (p = 0.0005). Moreover, patients with the FMO3 E308G genotype were more likely to have adverse drug reactions and abnormal serum parameters after receiving VRC treatment. For example, the serum potassium level in the FMO3 E308G genotype group was significantly lower than that in the WT group (p = 0.028), the abnormal level of total bilirubin in the FMO3 E308G genotype group was significantly higher than that in the WT group (p = 0.049), and the aspartate aminotransferase level in the E308G group was significantly higher than that in the WT group (p = 0.05). The incidence of atopic dermatitis and visual impairment in the FMO3 E308G genotype group was 67 and 75%, respectively, and the incidences of peripheral neuroedema, headache, and diarrhea were 57, 50, and 60%, respectively, which were significantly different from those in the WT group. CONCLUSION: FMO3 E308G reduces the activity of the FMO3 enzyme by decreasing the metabolic ability of VRC, which increases the plasma concentration of VRC and may also lead to adverse reactions in patients with FN.

Comparison of CRP and procalcitonin for etiological diagnosis of fever during febrile neutropenia in hematology patients- an experience from a tertiary care center in Northern India.

INTRODUCTION: Febrile neutropenia is a common cause in morbidity and mortality during treatment of hematological neoplasms. METHODS: Subjects included all cases admitted under hematology department with febrile neutropenia from February to June 2018. Each febrile episode was investigated by standard investigations (Blood culture, Chest x ray etc.); Procalcitonin (PCT) and c reactive protein (CRP) was sent at fever onset 0, 24, 48 h, day 7 and day 14. RESULTS: Data was analyzed for 52 febrile episodes in 50 patients. PCT cut off value at 24 h of ≤1.2 ng/ml had a sensitivity and specificity of 62.5% and 87.5% for discriminating Invasive fungal infection (IFI) and Microbiologically documented infection (MDI) (p = 0.033). PCT had a negative predictive value of 70% for the diagnosis of IFI as compared to MDI. CRP cut off >160 mg/dl at 48 h was suggestive of fever due to fungal infection with a sensitivity of 100%, specificity of 48%, PPV of 33.3% and NPV of 100%. CRP at 24 and 48 h of fever was useful to distinguish non-infectious causes of fever from infectious causes. CONCLUSION: PCT at 24 h and CRP at 48 h was useful in identifying fungal infection. CRP was a better marker when compared to PCT for identifying disease fever.

Plasma level of interleukin-18 and complicated course of febrile neutropenia in hematological patients after intensive chemotherapy.

In search of a biomarker for complicated course of febrile neutropenia (FN), plasma IL-18 was measured in 92 hematological patients after intensive chemotherapy at the beginning of FN (days 0-3). Complicated course was defined as blood culture positivity or septic shock. IL-18 varied according to background hematological malignancy and showed an inverse correlation with leukocyte count. IL-18 was not associated with complicated course of FN, defined as blood culture positivity or septic shock, in the whole study group, but an association was observed on d1 and d2 after the onset of FN in the subgroup of autologous stem cell transplant recipients with non-Hodgkin lymphoma.

An eleven-year cohort of bloodstream infections in 552 febrile neutropenic patients: resistance profiles of Gram-negative bacteria as a predictor of mortality.

Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum ß-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.

Increased Arbekacin Clearance in Patients With Febrile Neutropenia.

BACKGROUND: Arbekacin (ABK) is used to treat infections caused by methicillin-resistant Staphylococcus aureus and is used widely for the treatment of febrile neutropenia (FN). As ABK has a narrow therapeutic concentration window, the dosage must be adjusted via therapeutic drug monitoring. However, the influence of the physiology of patients with FN on the pharmacokinetic (PK) parameters of ABK remains unclear. Therefore, we examined this influence on ABK PK parameters. METHOD: We performed a retrospective cohort study using data from patients with a hematologic malignancy who were ≥18 years and had been administered ABK. We excluded patients who did not receive therapeutic drug monitoring and had an estimated glomerular filtration rate (eGFR) of <30 mL/min, because clinically sufficient data would not be available. RESULT: Of the 99 enrolled patients, 25 did not have FN and 74 had FN. Arbekacin clearance (CLabk) was shown to correlate with eGFR in patients with FN (r = 0.32, P = 0.0062) and without FN (r = 0.50, P = 0.01). CLabk was higher in patients with FN than in those without FN. In addition, in the eGFR of <100 mL/min group (normal renal function), CLabk and CLabk/eGFR were also higher in patients with FN than in those without FN. CONCLUSIONS: CLabk was increased in patients with FN and normal renal function; therefore, we propose an increased ABK dose for patients with FN and normal renal function.

Is current initial empirical antibiotherapy appropriate to treat bloodstream infections in short-duration chemo-induced febrile neutropenia?

INTRODUCTION: Fever of unknown origin is by far the most common diagnosis in low-risk febrile neutropenic patients undergoing chemotherapy. The current empirical regimen combines amoxicillin-clavulanic acid and fluoroquinolones in low-risk neutropenic patients. The aim of this study was to assess the appropriateness of antibiotherapy and the outcome of bloodstream infections (BSI) in patients with expected neutropenia of short duration. METHODS: This 2-year monocentric retrospective study included all consecutive neutropenic febrile adult patients with expected duration of neutropenia ≤ 7 days. They were classified into low- and high-risk groups for complications using the MASCC index. Appropriateness of initial empirical antibiotic regimen was assessed for each BSI. Multivariate analysis was performed to identify factors associated with mortality. RESULTS: Over the study period, 189 febrile episodes with positive blood cultures in neutropenic patients were reported, of which 44 occurred during expected duration of neutropenia ≤ 7 days. Patients were classified as high-risk (n = 27) and low-risk (n = 17). Gram-negative bacteria BSI represented 57% of cases, including only two multidrug-resistant bacteria in high-risk patients. Initial empirical antibiotherapy was appropriate in 86% of cases, and inappropriate in the event of coagulase-negative Staphylococcus BSI (14%), although the outcome was always favorable. In low-risk patients, no deaths and only 12% of severe complications were reported, contrasting with mortality and complication rates of 48% (p < 0.001) and 63% in high-risk patients (p < 0.001), respectively. CONCLUSIONS: Outcome of BSI is favorable in low-risk febrile neutropenic patients, even with inappropriate empirical initial antibiotic regimen for coagulase-negative Staphylococcus BSI. Initial in-hospital assessment and close monitoring of these patients are however mandatory.

Efficacy and safety of granulocyte transfusion in children: A single-center experience.

BACKGROUND: Granulocyte suspension transfusion (GTx) can be used in severely neutropenic patients with infections that cannot be controlled despite appropriate antibiotic therapy. OBJECTIVE: We aimed to evaluate the effectiveness and safety of GTx for the treatment of febrile neutropenia (FEN) in the pediatric age group. METHODS: Patients who underwent GTx in the Hematology Clinic of Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital between 2013 and 2017 were evaluated retrospectively. Hematologic and clinical response rates, effects on survival, and adverse effects were investigated. Clinical response was defined at two time points: clinical response I was evaluated after each transfusion, while clinical response II was evaluated after the final GTx in a FEN episode. RESULTS: During the study period, 343 GTx were given 107 FEN episodes of 74 patients. The mean number of granulocyte suspensions administered per patient and per FEN episode was 4.6 units and 3.2 units. The mean GTx volume administered was 237 ± 40 mL, and the mean granulocyte count was 2.8 ± 1.3 x 1010 /unit. Hematologic response was attained in 163 (47.6%) of 343 transfusions. Clinical response I was obtained in 88 (25.7%) of the GTx, and clinical response II was attained in 83 (78.5%) of 107 episodes. Life-threatening adverse event was not observed. The cumulative 1-month and 3-month survival rates were 87.8% and 76.5%, respectively. CONCLUSION: High hematologic response and clinical recovery rates were achieved with GTx, with no limiting adverse effects. Granulocyte transfusion appears to be a safe and effective treatment in pediatric patients with FEN.

Efficacy and safety of micafungin in unrelated cord blood transplant recipients.

Micafungin (MCFG) is an echinocandin antifungal drug used for prophylaxis and treatment of fungal infections after allogeneic hematopoietic cell transplantation (HCT). However, its efficacy and safety in patients undergoing cord blood transplantation (CBT) has not been clarified. We retrospectively analyzed the efficacy and safety of MCFG in 92 adult patients undergoing CBT in our institute. Of the entire cohort, 83 patients (90%) received MCFG for empirical or preemptive therapy. Documented breakthrough fungal infection occurred in 2 patients during MCFG treatment. Among the 49 patients who received MCFG as empirical therapy for febrile neutropenia, 41 (84%) patients had resolution of fever during neutropenia. Elevation of serum levels of hepatobiliary parameters during MCFG treatment was commonly observed, but grade 3 or higher elevation was rare. We also compared the efficacy and safety of 2 different initial daily doses of MCFG (150 mg vs. 300 mg). There were no significant differences of efficacy and safety between the two groups. These data suggest that MCFG was effective and safe for adult patients undergoing CBT. The optimal daily dose of MCFG treatment is a matter of future investigation for adult patients undergoing CBT.

Updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer.

Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review assesses the predictive role of biomarkers in identifying events such as bacteraemia, clinically documented infections, microbiologically documented infection, severe sepsis requiring intensive care or high dependency care and death. This review collates 8319 episodes from 4843 patients. C-reactive protein (CRP), interleukin (IL)-6, IL-8 and procalcitonin (PCT) consistently predict bacteraemia and severe sepsis; other outcomes have highly heterogeneous results. Performance of the biomarkers at admission using different thresholds demonstrates that PCT > 0.5 ng/mL offers the best compromise between sensitivity and specificity: sensitivity 0.67 (confidence interval [CI] 0.53-0.79) specificity 0.73 (CI 0.66-0.77). Seventeen studies describe the use of serial biomarkers, with PCT having the greatest discriminatory role. Biomarkers, potentially with serial measurements, may predict adverse outcomes in paediatric febrile neutropenia and their role in risk stratification is promising.

Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia.

Background Early diagnosis of infection is essential for the initial management of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this study, we have evaluated two emerging infection biomarkers, pancreatic stone protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of differentiation 25 (sCD25), for the detection of an infectious cause in FN, in comparison with other commonly used infection biomarkers, such as procalcitonin (PCT). Methods A total of 105 cancer patients presenting to the emergency department were prospectively enrolled. We observed 114 episodes of chemotherapy-associated FN. At presentation, a blood sample was collected for the measurement of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these markers for the diagnosis of infection, the area under the curve (AUC) of the receiver operating characteristic curves was calculated. Results Infection was documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher in infected patients. PCT was the biomarker with the highest diagnostic accuracy for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance, with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and sCD25 were shown to be independently associated with infection. Conclusions Two novel biomarkers, PSP and sCD25, correlated with infection in cancer patients with chemotherapy-associated FN, but neither PSP nor sCD25 improved the performance of PCT. Based on the results obtained, the introduction of these novel biomarkers as a tool for the diagnosis of infection in this patient group is not recommended.

Serum biomarkers for sepsis in children with febrile neutropenia and cancer.

The National Institute for Health and Care Excellence (NICE) defines febrile neutropenia or "neutropenic sepsis" as a patient with an absolute neutrophil count (ANC) less than 0.5 x 109/L and temperature >38°C or signs and symptoms of sepsis.

Evaluation of the effectiveness of caspofungin against febrile neutropenia and the factors related to the alteration in its plasma concentration.

Caspofungin (CPFG) is an echinocandin antifungal agent that inhibits the synthesis of ß-1, 3-D-glucan, a critical component of the cell wall of target fungi. Several clinical studies have confirmed the efficacy and safety of CPFG in patients with febrile neutropenia (FN); however, there are no reports available in Japanese patients with FN. Therefore, we investigated the therapeutic efficacy and pharmacokinetics of CPFG as an empirical therapy in a Japanese hospital. Twenty-four Japanese patients, who were diagnosed with FN at Gifu University Hospital from February 2014 to August 2017, were enrolled. Blood samples were collected at the end of CPFG dosing (0.5 h after the infusion) on day 1 and immediately prior to the next infusion on days 2, 3, and 4. The concentration of CPFG in plasma was measured by high-performance liquid chromatography. The efficacy was assessed by five of the component endpoints, and safety was monitored according to the Common Terminology Criteria for Adverse Events. CPFG showed an excellent effect against FN (75%, 18/24), without any serious hepatic or renal toxicity. Regarding the pharmacokinetics, the plasma concentration of CPFG was significantly correlated with body weight; although, no correlation was observed between the plasma concentration of CPFG and the other factors investigated, such as gender or laboratory results. These results suggest the high efficacy, safety, and tolerability of CPFG as an empirical antifungal therapy for Japanese patients with FN.