Search Results (22)

Background/Objectives: Febrile neutropenia is a frequent and potentially life-threatening complication in pediatric oncology patients receiving chemotherapy. Due to profound immunosuppression, early diagnosis of infections remains a major clinical challenge. This review evaluates the diagnostic and prognostic utility of infection biomarkers in children with chemotherapy-induced severe neutropenia. Methods: We reviewed clinical studies that assessed the diagnostic performance of inflammatory biomarkers—including C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8, IL-10), and others—in pediatric febrile neutropenia. The review includes data on sensitivity, specificity, predictive value, and clinical applications. Results: CRP remains a common but nonspecific marker, often insufficient for early stratification. PCT showed consistently high negative predictive value and early responsiveness to bacterial infections. IL-6 and IL-10 demonstrated strong early diagnostic accuracy in the early phase (AUC > 0.80 in multiple studies) and were particularly useful in predicting septic shock when combined. IL-8, while less specific, may help rule out infection when levels are low. Emerging biomarkers such as presepsin, MR-proADM, and PSP showed promising diagnostic performance. Presepsin achieved near-perfect accuracy in some cohorts (AUC up to 0.996), outperforming CRP and PCT, though its ability to discriminate bacteremia at fever onset varied. MR-proADM demonstrated consistent AUCs above 0.75 and may support early sepsis identification. PSP was associated with significantly elevated levels in sepsis. Additional novel markers—including sTNFR-II, sIL-2R, IP-10, Flt-3L, MCP-1-a, and MBL—showed encouraging diagnostic profiles in individual studies, particularly due to high specificity, but require external validation. G-CSF also emerged as a promising candidate in multimarker models. In contrast, TNF-α and IL-1β displayed limited utility as standalone indicators. Conclusions: Biomarkers such as PCT, IL-6, Il-8, and IL-10 offer valuable tools for early infection detection and risk stratification in pediatric febrile neutropenia. Emerging markers—including presepsin, MR-proADM, and PSP—further enhance diagnostic precision and may support early identification of sepsis. Multimarker strategies, particularly those incorporating presepsin, IL-10, or MR-proADM, show potential to improve diagnostic performance beyond conventional markers. Further prospective validation is needed to optimize clinical implementation and guide personalized treatment decisions. Full article

The routine use of granulocyte colony-stimulating factor (GCSF) is not recommended for the prevention or treatment of chemotherapy-induced neutropenia or febrile neutropenia because risks associated with certain types of cancers, distant organ metastases, and primary tumor growth cannot be excluded. We examined the association between GCSF use and the incidence of brain metastasis (BM), as well as BM-free survival (BMFS). This retrospective cohort study included 121 stage IV breast cancer patients without confirmed BM at the time of diagnosis and who received at least one course of systematic chemotherapy or target therapy at a tertiary teaching hospital between 1 January 2014 and 31 December 2022. The effect of GCSF use on BM was assessed with other confounding factors in Cox regression analyses. In this retrospective cohort, patients who received GCSF treatment had a significantly higher incidence of BM than those who did not (34.9% vs. 13.8%, p = 0.011). Univariate Cox regression analysis showed that GCSF use, menopause status, hormone treatment, HER2 treatment, cumulative dosage, dosage density, and neutropenia were independent risk factors for BMFS (p < 0.05). GCSF users had a higher risk of BM (adjusted HR: 2.538; 95% CI: 1.127–5.716, p = 0.025) than nonusers. BM risk was significantly associated with those with neutropenia (RR: 1.84, 95% CI: 1.21, 2.80) but not with those without neutropenia (RR: 0.59, 95% CI: 0.41–0.84, Interaction p-value < 0.05). The higher the dose density of GCSF, the higher the risk compared with those who do not use GCSF (p for trend < 0.01). These preliminary results suggest that GCSF is associated with BM in patients with stage IV breast cancer who did not have BM at initial diagnosis. Further comprehensively designed large-scale observational studies are needed to confirm our preliminary results. Full article

Patients with breast cancer undergoing chemotherapy are susceptible to prolonged and severe neutropenia. Multiple biosimilars of long-acting granulocyte colony-stimulating factors (LA-G-CSFs) have been newly developed to prevent this disease. Nonetheless, which LA-G-CSF regimen has the optimal balance of efficacy and safety remains controversial. Moreover, there is a lack of evidence supporting clinical decisions on LA-G-CSF dose escalation in poor conditions. PubMed, Embase, Cochrane Library, Web of Science, and several Chinese databases were searched (December 2022) to collect randomized controlled trials (RCTs) about LA-G-CSFs preventing chemotherapy-induced neutropenia in breast cancer patients. No restrictions were imposed on language. A Bayesian network meta-analysis was performed. We assessed the incidence of severe neutropenia (SN) and febrile neutropenia (FN), the duration of SN (DSN), and the absolute neutrophil account recovery time (ANCrt) for efficacy, while the incidence of severe adverse events (SAE) was assessed for safety. The study was registered in PROSPERO (CRD42022361606). A total of 33 RCTs were included. Our network meta-analysis demonstrated that lipegfilgrastim 6 mg and eflapegrastim 13.2 mg outperformed other LA-G-CSFs with high efficacy rates and few safety concerns (SUCRA of lipegfilgrastim 6 mg: ANC rt 95.2%, FN 97.4%; eflapegrastim 13.2 mg: FN 87%, SN 89.3%). Additionally, 3.6 mg, 4.5 mg, 6 mg, and 13.2 mg dosages all performed significantly better than 1.8 mg in reducing the duration of SN (3.6 mg: DSN, SMD −0.68 [−1.13, −0.22; moderate]; 4.5 mg: −0.87 [−1.57, −0.17; low]; 6 mg: −0.89 [−1.49, −0.29; moderate]; 13.2 mg: −1.02 [1.63, −0.41; high]). Increasing the dosage from the guideline-recommended 6 mg to 13.2 mg can reduce both the duration and incidence of SN (SMD −0.13 [−0.24 to −0.03], RR 0.65 [0.43 to 0.96], respectively), with no significant difference in SAE. For patients with breast cancer, lipegfilgrastim 6 mg and eflapegrastim 13.2 mg might be the most effective regimen among LA-G-CSFs. Higher doses of LA-G-CSF may enhance efficacy without causing additional SAEs. Full article

The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HR_Malay [95% CI]:2.04 [1.44–2.88], p < 0.001; HR_Indian:1.88 [1.11–3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities’ risk (HR_Malay:1.29 [1.07–1.54], p = 0.006; HR_Indian:1.50 [1.19–1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities. Full article

Chemotherapy-induced febrile neutropenia (FN) is a medical emergency that causes severe adverse effects and death. Respiratory infections are one of the main causes of fever in patients with FN. We studied whether infection prevention and control (IPC) guidance for coronavirus 2019 disease reduced the incidence of FN. We reviewed female patients with breast cancer treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide with prophylactic pegfilgrastim between 2019 and 2021. IPC guidance was implemented in April 2020. There was no difference in the incidence of chemotherapy-induced neutropenia between patients with and without IPC. In patients with IPC, the incidence of FN (9.5%) was lower than that of patients without IPC (27.9%). The hospitalization duration (0.7 ± 1.5 days) and total hospital cost (279.6 ± 42.6 USD) of the IPC group were significantly lower than that of the non-IPC group (2.0 ± 3.8 days and 364.7 ± 271.6 USD, respectively). IPC guidance should be implemented to prevent FN in high-risk patients with breast cancer. Full article

Haematological patients represent a vulnerable population to opportunistic infections, mainly due to the disease itself and chemotherapy-induced neutropenia. The level of immune suppression strongly increases the importance of timely antibiotic treatment in order to prevent sepsis-related mortality. During the initial fever episode, serum biomarkers are usually used to estimate the probability of blood stream infection prior to the results of microbial diagnosis. A new serum biomarker combination study on a febrile haematological population, including C-reactive protein (CRP), interleukin-6 (IL−6) and procalcitonin (PCT), is proposed in order to improve their predictive accuracy. In our prospective study, CRP, IL−6 and PCT were evaluated in 34 immunosuppressed haematological patients immediately after the onset of 51 fever episodes, either during the course of standard chemotherapy or high-dose chemotherapy and autologous stem cell transplant. The fever episodes were divided into documented infections and fever alone. Receiver operating characteristic analysis (ROC) was performed for each biomarker and a combination of all three biomarkers (multiROC) to define a new predictive index. Significant differences were evidenced between the two groups (documented infection and no infection) for both PCT and IL−6 (p = 0.03 and p = 0.035, respectively), but none for CRP (p = 0.1). The composite parameter is more reliable than any single biomarker alone, with an area under the curve (AUC) of 79% and with high sensitivity and specificity. IL−6 gave the closest response compared to the composite index. Composite parameters of serum biomarkers could be used for an early diagnosis of infection at fever onset in haematological patients. Full article

Previous research has determined that the required doses for treating febrile neutropenia with vancomycin are higher than the doses used conventionally. These recommendations have been made considering pharmacotherapeutic goals based on minimum concentration (${\mathrm{C}}_{\min }$) between 15–20 $\mathrm{mg}/\mathrm{L}$. This study was developed to evaluate dose recommendations based on the achievement of a target consisting of ratio of area under the curve over minimum inhibitory concentration (${\mathrm{AUC}}_{24\mathrm{h}}/\mathrm{MIC}$) $\ge 400$ in this population of individuals. This study was conducted in a referral hospital for cancer treatment, study participants received vancomycin doses of $1\mathrm{g}$ every 12 h in 2-4-h infusions. Vancomycin was described by a two-compartment pharmacokinetic model with clearance dependent on the estimated glomerular filtration rate. Simulations were performed taking into account a reduced version of the model to establish the influence of controllable and non-controllable variables on the probability of achieving several PK-PD targets. A dose of $2.5\mathrm{g}/\mathrm{day}$ in patients with estimated glomerular filtration rate ($\mathrm{eGFR}$) between 80 and $122\mathrm{mL}/\min /1.73{\mathrm{m}}^2$ was adequate to achieve the pharmacotherapeutic target. A discrepancy was found between $\mathrm{AUC}$-based and ${\mathrm{C}}_{\min }$-based PK/PD indices, the former being affected by the dose and creatinine clearance while the latter highly influenced by the interval between doses. Full article

Background and Objectives: Chemotherapy-induced febrile neutropenia is the most widespread oncologic emergency with high morbidity and mortality rates. Herein we present a retrospective risk factor identification study to evaluate the prognostic role of lymphocyte-based measures and ratios in a cohort of chemotherapy-induced febrile neutropenia patients following granulocyte colony-stimulating factor (G-CSF) therapy. Materials and Methods: The electronic medical records at our center were utilized to identify patients with a first attack of chemotherapy-induced febrile neutropenia and were treated accordingly with G-CSF between January 2010 to December 2020. Patients’ demographics and disease characteristics along with laboratory tests data were extracted. Prognosis-related indicators were the absolute neutrophil count (ANC) at admission and the following 6 days besides the length of stay and mortality rate. Results: A total of 80 patients were enrolled, which were divided according to the absolute lymphocyte count at admission into two groups, the first includes lymphopenia patients (n = 55) and the other is the non-lymphopenia group (n = 25) with a cutoff point of 700 lymphocytes/μL. Demographics and baseline characteristics were generally insignificant among the two groups but the white blood cell count was higher in the non-lymphopenia group. ANC, neutrophils percentage and ANC difference in reference to admission among the two study groups were totally insignificant. The same insignificant pattern was observed in the length of stay and the mortality rate. Univariate analysis utilizing the ANC difference compared to the admission day as the dependent variable, revealed no predictability role in the first three days of follow up for any of the variables included. However, during the fourth day of follow up, both WBC (OR = 0.261; 95% CI: 0.075, 0.908; p = 0.035) and lymphocyte percentage (OR = 1.074; 95% CI: 1.012, 1.141; p = 0.019) were marginally significant, in which increasing WBC was associated with a reduction in the likelihood of ANC count increase, compared to the lymphocyte percentage which exhibited an increase in the likelihood. In comparison, sequential ANC difference models demonstrated lymphocyte percentage (OR = 0.961; 95% CI: 0.932, 0.991; p = 0.011) and monocyte-to-lymphocyte ratio (OR = 7.436; 95% CI: 1.024, 54.020; p = 0.047) reduction and increment in the enhancement of ANC levels, respectively. The fifth day had WBC (OR = 0.790; 95% CI: 0.675, 0.925; p = 0.003) to be significantly decreasing the likelihood of ANC increment. Conclusions: we were unable to determine any concrete prognostic role of lymphocyte-related measures and ratios. It is plausible that several limitations could have influenced the results obtained, but as far as our analysis is concerned ALC role as a predictive factor for ANC changes remains questionable. Full article

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disorder that occurs due to immunologic dysregulation. HLH can be primary (hereditary) or secondary to infections, autoimmune diseases, immune deficiencies, metabolic diseases, drugs, or malignancies. Lymphoid neoplasms mostly accompany malignancy-associated HLH. We present a case of a 12-year-old boy with a history of precursor B lymphoblastic leukemia (B-ALL), who subsequently developed chemotherapy-induced acute myeloid leukemia (t-AML). The patient was admitted for febrile neutropenia and initial laboratory tests revealed hemophagocytic lymphohistiocytosis (HLH). The hospital course was complicated by multiple infections and septic shock. The patient received several broad-spectrum antimicrobials, dexamethasone, as well as a pericardial drain to drain the hemorrhagic pericardial effusion. Despite intervention, the patient expired, and an autopsy was performed. We provide a synopsis of the main autopsy findings. Full article

Background: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients. Methods: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t-tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls. Results: PRS distributions were not significantly different in any of the comparisons. Higher PRS_overall quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79–1.06]; FNc: 0.87 [0.73–1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRS_ER-pos) and ER-negative weighted PRS (PRS_ER-neg). Conclusion: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc. Full article

The primary prophylaxis with filgrastim (FIL) and pegfilgrastim (PEG-F) is recommended to decrease the severity of chemotherapy-induced neutropenia (CIN). The commonly reported adverse drug reactions (ADRs) with FIL and PEG-F is bone pain. ADRs pertaining to FIL and PEG-F were extracted from the European EudraVigilance (EV) database. The Individual Case Safety Reports (ICSRs) obtained from EV database that reported FIL and PEG-F as the suspected drug were analyzed. Registered ADRs (from the groups “General disorders and administration site conditions”, “Blood and lymphatic system disorders”, “Musculoskeletal and connective tissue disorders” and “Investigations”) for FIL and PEG-F were collected from EV database from 2007 to 5 June 2021. The reporting odds ratio (ROR) was used to calculate ICSRs with most common ADRs related to FIL and PEG-F. A total of 17,403 ICSRs described the incidence of most common ADRs of FIL and PEG-F. The commonly reported ADRs for both drugs were pyrexia, bone pain, back pain, neutropenia and febrile neutropenia. The odds ratio of ICSRs belonging to the System Organ Class (SOC) “Investigations” (ROR 1.01 (CI 0.93–1.10)) revealed no significant difference in FIL and PEG-F. However, for the SOCs (General disorders and administration site conditions” and “Musculoskeletal and connective tissue disorders” ((ROR 1.14 (CI 1.06–1.21); ROR 1.21 (CI 1.18–1.32), respectively), an increased reporting probability with PEG-F was found. The authors reported a lower reporting probability for the SOC “Blood and lymphatic system disorders” for FIL versus PEG-F (ROR 0.75 (CI 0.70–0.80)). Our results have demonstrated that the occurrence of bone pain was similar with FIL and PEG-F. For the incidence of pyrexia and back pain, PEG-F was associated with a higher reporting probability as compared to FIL. However, the incidence of neutropenia and febrile neutropenia was higher in FIL compared to PEG-F. Further evaluation of data from real life is needed. Full article

Patients with chemotherapy-induced febrile neutropenia (CIFN) may have changes in the pharmacokinetics (PK) compared to patients without malignancies or neutropenia. Those changes in antibiotic PK could lead to negative outcomes for patients if the therapy is not adequately adjusted to this. In this, open-label, non-randomized, prospective, observational, and descriptive study, a PK model of cefepime was developed for patients with hematological neoplasms and post-chemotherapy febrile neutropenia. This study was conducted at a cancer referral center, and study participants were receiving 2 g IV doses of cefepime every 8 h as 30-min infusions. Cefepime PK was well described by a two compartment model with a clearance dependent on a serum creatinine level. Using Monte Carlo simulations, it was shown that continuous infusions of 6g q24h could have a good achievement of PK/PD targets for MIC levels below the resistance cut-off point of Enterobacteriaceae. According to the simulations, it is unnecessary to increase the daily dose of cefepime (above 6 g daily) to increase the probability of target attainment (PTA). Cumulative fraction of response (CFR) using interment dosing was suboptimal for empirical therapy regimens against K. pneumoniae and P. aeruginosa, and continuous infusions could be used in this setting to maximize exposure. Patients with high serum creatinine levels were more likely to achieve predefined PK/PD targets than patients with low levels. Full article

The antibiotic stewardship program (ASP) is a necessary part of febrile neutropenia (FN) treatment. Pharmacist-driven ASP is one of the meaningful approaches to improve the appropriateness of antibiotic usage. Our study aimed to determine role of the pharmacist in ASPs for FN patients. We prospectively studied at Thammasat University Hospital between August 2019 and April 2020. Our primary outcome was to compare the appropriate use of target antibiotics between the pharmacist-driven ASP group and the control group. The results showed 90 FN events in 66 patients. The choice of an appropriate antibiotic was significantly higher in the pharmacist-driven ASP group than the control group (88.9% vs. 51.1%, p < 0.001). Furthermore, there was greater appropriateness of the dosage regimen chosen as empirical therapy in the pharmacist-driven ASP group than in the control group (97.8% vs. 88.7%, p = 0.049) and proper duration of target antibiotics in documentation therapy (91.1% vs. 75.6%, p = 0.039). The multivariate analysis showed a pharmacist-driven ASP and infectious diseases consultation had a favorable impact on 30-day infectious diseases-related mortality in chemotherapy-induced FN patients (OR 0.058, 95%CI:0.005–0.655, p = 0.021). Our study demonstrated that pharmacist-driven ASPs could be a great opportunity to improve antibiotic appropriateness in FN patients. Full article

Data on the use of Granulocyte colony-stimulating factor (G-CSF) in pregnant cancer patients are scarce. The International Network of Cancer, Infertility and Pregnancy (INCIP) reviewed data of pregnant patients treated with chemotherapy and G-CSF, and their offspring. Among 2083 registered patients, 42 pregnant patients received G-CSF for the following indications: recent chemotherapy induced febrile neutropenia (5; 12%), dose dense chemotherapy (28, 67%), poly chemotherapy (7, 17%), or prevention of neutropenia at delivery (2; 5%). Among 24 women receiving dose dense chemotherapy, three (13%) patients recovered from asymptomatic neutropenia within 5 days. One patient developed pancytopenia following polychemotherapy after which the pregnancy was complicated by chorioamnionitis and intrauterine death. Nineteen singleton livebirths (49%) were born preterm. Sixteen neonates (41%) were admitted to the Neonatal Intensive care Unit (NICU). No neonatal neutropenia occurred. Two neonates had congenital malformations. Out of 21 children in follow-up, there were four children with a motor development delay and two premature infants had a delay in cognitive development. In conclusion, the rate of maternal and neonatal complications are similar to those described in (pregnant) women treated with chemotherapy. Due to small numbers and limited follow-up, rare or delayed effects among offspring exposed to G-CSF in utero cannot be ruled out yet. Full article

In children with cancer, chemotherapy can produce cytotoxic effects, resulting in immunosuppression and an augmented risk of febrile neutropenia and bloodstream infections. This has led to widespread use of antibiotic prophylaxis which, combined with intensive chemotherapy treatment, could have a long-term effect on the gastrointestinal microbiome. In this review, we aimed to analyze the current literature about the widespread use of antibiotic prophylaxis in children experiencing infectious complications induced by chemotherapy and its effects on the gut microbiome. Our review of the literature shows that antimicrobial prophylaxis in children with cancer is still a trending topic and, at the moment, there are not enough data to define universal guidelines. Children with cancer experience long and painful medical treatments and side effects, which are associated with great economic and social burdens, important psychological consequences, and dysbiosis induced by antibiotics and also by chemotherapy. Considering the importance of a healthy gut microbiota, studies are needed to understand the impact of dysbiosis in response to therapy in these children and to define how to modulate the microbiome to favor a positive therapeutic outcome. Full article