Febrile Neutropenia Research Articles

Clinical drug interactions between voriconazole and 38 other drugs: a retrospective analysis of adverse events.

Voriconazole (VRZ) is involved in a variety of drug‒drug interactions (DDIs), but few studies have reported adverse events (AEs) associated with the DDIs of VRZ. The primary goal of this study was to analyse the potential risk factors for AEs caused by DDIs between VRZ and other drugs via the OpenVigil FDA platform and to provide a reference for preventing VRZ DDIs and monitoring clinically related adverse drug events. A retrospective pharmacovigilance study was conducted to investigate the AEs related to DDIs between VRZ and four categories of drugs: proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants, and other antibacterial drugs. AE information for the target drugs from the first quarter of 2004 to the third quarter of 2022 was downloaded from the OpenVigil FDA data platform. Four frequency statistical models-the reporting ratio method, Ω shrinkage measure model, combination risk ratio model, and the chi-square statistics model-were used to analyse the AEs related to DDIs and evaluate the correlation and influence of sex and age between the drug(s) and the target AEs detected. A total of 38 drugs were included, with 262 AEs detected by at least one of the four models and 48 AEs detected by all four models. Some 77 detected AEs were significantly positively correlated with DDIs and were related to higher reporting rates of AEs than when used alone. Graft-versus-host disease was the AE that had the strongest correlation with the drug interaction between VRZ and immunosuppressants (tacrolimus, mycophenolate mofetil, cyclophosphamide, and cyclosporine), and multiple organ dysfunction syndrome was correlated with VRZ in combination with other antibacterial drugs (linezolid, meropenem, cefepime, and vancomycin). Significant sex and age differences in the target AEs were detected for five and nine target drugs, respectively. For VRZ in combination with linezolid, aggravated conditions and respiratory failure should be given more attention in male patients, and mycophenolate mofetil and respiratory failure in female patients. When conditions are aggravated, febrile neutropenia and septic shock should be of particular concern in patients over 18years of age who use VRZ in combination with ceftazidime, ciprofloxacin, or cytarabine. In patients aged under 18, septic shock should be considered when VRZ is used in combination with meropenem and dexamethasone. AEs related to DDIs should receive more attention when VRZ is used in combination with PPIs (renal impairment), NSAIDs (constipation and renal failure), immunosuppressants (graft versus host disease, septic shock) and other antibacterial drugs (multiple organ dysfunction syndrome, febrile neutropenia, and respiratory failure). Considering the influence of sex and age differences in VRZ DDIs, these factors need to be considered when assessing the risk of AEs in patients receiving VRZ and other drugs.

Eribulin plus carboplatin combination for HER2-negative metastatic breast cancer: a multicenter, real-world cohort study

BackgroundPre-clinical data suggests a potential synergistic effect of eribulin and platinum. However, clinical data on the combination for metastatic breast cancer (mBC) is lacking. We evaluated the efficacy and safety of eribulin plus carboplatin (ErCb) in patients with mBC.Patients and methodsThis multicenter, real-world cohort study included patients with pre-treated metastatic triple negative breast cancer (TNBC) or endocrine-refractory hormone receptor (HR) positive, HER2-negative mBC who received ErCb. Eribulin (1.4 mg/m2) and carboplatin (target AUC = 2) were administered intravenously on day 1 and 8 of 21-day cycle. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.ResultsFrom March 2022 to December 2023, a cohort of 37 patients were recruited to the study. Among them, 22 patients have TNBC and 15 have HR + HER2 − mBC. Of the 22 patients with TNBC, 8 had an initial diagnosis of the HR + HER2 − subtype. The median treatment was 6 cycles (range, 2 − 8 cycles). In the full cohort, TNBC, and HR + HER2 − subgroup, the ORR were 51.4%, 54.5% and 46.7%, the DCR were 81.1%, 81.8% and 80%, and the median PFS were 5 months, 5 months, and 5.2 months, respectively. The median OS was 12.7 months in the entire cohort and 12.8 months in TNBC subgroup. The most common grade 3/4 hematological AEs were neutropenia (37.8%), leukopenia (35.1%), febrile neutropenia (10.8%), thrombocytopenia (5.4%), and anemia (2.7%). No grade 3/4 non-hematological AEs were observed.ConclusionErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.

Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial

Ziftomenib (KO-539) is an oral selective menin inhibitor with known preclinical activity in menin-dependent acute myeloid leukaemia models. The primary objective of this study was to determine the recommended phase 2 dose in patients with relapsed or refractory acute myeloid leukaemia based on safety, pharmacokinetics, pharmacodynamics, and preliminary activity. KOMET-001 is a multicentre, open-label, multi-cohort, phase 1/2 clinical trial of ziftomenib in adults with relapsed or refractory acute myeloid leukaemia. Results of the phase 1 study, conducted at 22 hospitals in France, Italy, Spain, and the USA, are presented here and comprise the dose-escalation (phase 1a) and dose-validation and expansion (phase 1b) phases. Eligible patients were aged 18 years or older, had relapsed or refractory acute myeloid leukaemia, and had an Eastern Cooperative Oncology Group performance status of 2 or less. For phase 1a, patients (all molecular subtypes) received ziftomenib (50-1000 mg) orally once daily in 28-day cycles. For phase 1b, patients with NPM1 mutations or with KMT2A rearrangements were randomly assigned (1:1) using third-party interactive response technology to two parallel dose cohorts (200 mg and 600 mg ziftomenib). Primary endpoints were maximum tolerated dose or recommended phase 2 dose in phase 1a, and safety, remission rates, and pharmacokinetics supporting recommended phase 2 dose determination in phase 1b. Analyses were performed in all patients who received at least one dose of ziftomenib (modified intention-to-treat population). Phase 1a/1b is complete. This trial is registered with ClinicalTrials.gov, NCT04067336, and the EU Clinical Trials register, EudraCT 2019-001545-41. From Sept 12, 2019, to Aug 19, 2022, 83 patients received 50-1000 mg ziftomenib (39 [47%] were male and 44 [53%] were female). Median follow-up was 22·3 months (IQR 15·4-30·2). Of 83 patients, the most common grade 3 or worse treatment-emergent adverse events were anaemia (20 [24%]), febrile neutropenia (18 [22%]), pneumonia (16 [19%]), differentiation syndrome (12 [15%]), thrombocytopenia (11 [13%]), and sepsis (ten [12%]). Overall, 68 of 83 patients had serious adverse events, with two reported treatment-related deaths (one differentiation syndrome and one cardiac arrest). Differentiation syndrome rate and severity influenced the decision to halt enrolment of patients with KMT2A rearrangements. In Phase 1b, no responses were reported in patients treated at the 200 mg dose level. At the recommended phase 2 dose of 600 mg, nine (25%) of 36 patients with KMT2A rearrangement or NPM1 mutation had complete remission or complete remission with partial haematologic recovery. Seven (35%) of 20 patients with NPM1 mutation treated at the recommended phase 2 dose had a complete remission. Ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with relapsed or refractory acute myeloid leukaemia. Phase 2 assessment of ziftomenib combination therapy in the upfront and relapsed or refractory setting is ongoing. Kura Oncology.

At-Home Care Versus Total Hospital Care Model for Autologous Stem Cell Transplantation in Adult Lymphoma Patients: A Pilot Case-Control Study.

Lymphoma is the second most prevalent cancer treated with autologous stem cell transplantation (ASCT). Additional resources are required to enhance the provision of care for these patients. To explore the complications and economic costs of home versus hospital care models for ASCT in patients diagnosed with lymphoma and to describe the experience of home care patients. This was an observational pilot case-control study with 1:1 matching, in which all patients assisted at home were included. Data were obtained by reviewing medical records and data from the hospital's financial and resource management service. The IEXPAC scale version 11 + 4 was used to assess the care process experience as perceived by home care patients. The study included 34 patients, in which there was a significant decrease in neutropenic fever, both in frequency and duration (P = .001 and P < .001, respectively), in mucositis days (P = .038), and the rate of red cell concentrate transfusion (P < .001); however, there was a longer neutrophil recovery time (P = .044) in home care versus hospitalized patients. The overall cost was higher in the hospital care model (P = .001). Home care patients obtained high scores on the perceived experience of the care process scale. The home ASCT model is associated with fewer complications, shorter hospital stays, and more significant cost savings. The experience of the home care process was rated satisfactorily. This study provides evidence for a model that offers high-quality care and a comfortable experience for ASCT patients. Preparing more nurses for this home care model is imperative.

Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma.

Optimal frontline use of active agents in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is prudent to improve outcomes. We report the long-term follow-up of the phase 2 trial of HyperCVAD with nelarabine and pegylated asparaginase (Original cohort). In the latest protocol iteration venetoclax was added to the induction/consolidation regimen (Venetoclax cohort). Eligible patients were adults with untreated T-ALL/LBL or after minimal therapy and with adequate organ function. Primary endpoint of this analysis was improvement in 2-year progression free survival (PFS) and overall survival (OS) with venetoclax. From Aug 2007 to Dec 2024, 145 patients, at a median age of 35.4 years, were treated; 46 (33.8%) were in the venetoclax cohort. At median follow-up (mFU) of 62.4 months, 5-year PFS, duration of response (DOR), and OS were 63.7%, 72.0% and 66.2% respectively. In the venetoclax cohort (mFU 24.4 months) 2-year PFS (87.9% versus 64.1%, p = 0.03) and 2-year DOR (93.6% versus 69.2%, p = 0.005) were superior to the original cohort (mFU 89.4 months) and 2-year OS appeared better (87.8% versus 73.9%, p = 0.16). Febrile neutropenia was the most common serious adverse event, seen in 60% patients. The addition of venetoclax to HyperCVAD-nelarabine-pegylated asparaginase was tolerable and led to improvement in DOR and PFS.

Tolerability and Outcomes for Treatment of Older Myxoid Liposarcoma Population.

Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. This single institution retrospective study included patients aged 70 years and older with localized (non-metastatic) myxoid liposarcoma. Sixteen patients were included. The median age was 75 years, and 9 (56%) were female. Fourteen (88%) were extremity tumors and two (12%) were trunk. The median tumor size was 10.4 cm (range, 3.6 to 28 cm). Five (31%) tumors had a round cell component. All patients had surgery. Fourteen (88%) had perioperative radiation, and three (19%) had perioperative chemotherapy. One patient had postoperative infection, and one patient had neutropenic fever from preoperative chemotherapy. The median follow up from surgery was 6.3 years. Eight (50%) patients died from MLPS. The median relapse-free survival and overall survival were 34 months and 75 months, respectively. Most older patients with localized MLPS received perioperative radiation therapy with surgery, and few serious toxicities were reported. Even with treatment, half of the patients relapsed.

Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA Adverse Event Reporting System

ABSTRACT Background The Phosphoinositide 3-kinases (PI3Ks) family plays a crucial role in tumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibiting PI3Kδ) were developed to target the PI3K pathway. However, the toxicity limits their application to some extent. It’s necessary to investigate the adverse effects (AEs) of these inhibitors. Research design and methods We conducted a comparative analysis of the safety signals of AEs in PI3K inhibitors using disproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). Results Our study identified significant safety signals for metabolic disorders with all PI3K inhibitors. Notable safety signals for gastrointestinal disorders were observed with most PI3K inhibitors, with the exception of copanlisib. Common AEs shared among all PI3K inhibitors included colitis and dehydration. Alpelisib displayed unique AEs associated with metabolic disorders, whereas copanlisib exhibited idiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnson syndrome emerged as a common severe adverse event (SAE) among alpelisib, copanlisib, and idelalisib, while febrile neutropenia was prevalent among copanlisib, duvelisib, and idelalisib. Intestinal perforation was solely associated with alpelisib. Conclusions The safety profiles of the five PI3K inhibitors vary concerning adverse events. These findings could guide drug selection and inform future prospective research.

Febrile neutropenia induced by adjuvant radiotherapy for a patient with breast cancer accompanied with reversible splenial lesion syndrome (RESLES, TypeI): a case report

BackgroundReversible splenial lesion syndrome (RESLES) is known as a neuro-imaging syndrome with recurrent but reversible lesion of the corpus callosum, characterized by nonspecific but usually mild encephalopathies and specific imaging manifestations.There are few published reports in the field of oncology.Case presentationA 33-year-old female with right breast cancer and with no particular family history was admitted to hospital with high fever and severe headache, after receiving adjuvant radiotherapy. Blood routine test upon admission suggested neutropenia, considering myelosuppression associated with radiotherapy. There were no definite findings of common pathogenic microorganism, and no imaging indication of certain infectious sites other than a likely reversible corpus callosum syndrome suggested by brain MRI, which was relieved after systemic antibiotic therapy and granulocyte colony-stimulating factor injection.ConclusionsReversible splenial lesion syndrome is a kind of clinical-imaging syndrome with multiple clinical manifestations and etiologies. This breast cancer patient after postoperative adjuvant radiotherapy develops a complication of RESLES that rings an alarm bell to the oncologists not to easily recognize the corpus callosum lesion as infarction or metastasis. Meanwhile, the potential pathogenic mechanisms need to be explored further.

Pembrolizumab in Japanese patients with primary mediastinal large B-cell lymphoma: results from the KEYNOTE-A33 study.

KEYNOTE-A33 (NCT04317066) is an open-label, single-arm, phase 1 trial designed to evaluate the safety and efficacy of pembrolizumab in Japanese patients with relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBCL). Patients received pembrolizumab 200mg every 3weeks for up to 35 cycles. The primary endpoints were safety and objective response rate (ORR) per International Working Group 2007 criteria by independent central review. The secondary endpoint was disease control rate (DCR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. Seven patients were enrolled and treated; the median age was 32years (range 26-43) and 86% were female. The median time from the first dose to data cutoff (April 12, 2022) was 5.6months (range 2.4-21.2). Grade 3-5 treatment-related adverse events (AEs) occurred in 2 patients (29%; 2 grade 4 neutropenia, 1 grade 3 febrile neutropenia); however, no patient discontinued pembrolizumab or died because of treatment-related AEs. The ORR was 43% [95% confidence interval (CI) 10-82]. DCR was 57% (95% CI 18-90). Median DOR was not reached (NR). Four (57%) patients had a reduction in target lesion size of ≥ 50%. The median PFS was 2.9months (95% CI 2.6-NR). The median OS was 17.5months (95% CI NE-NE), and the 12months OS rate was 100%. Overall, pembrolizumab had manageable safety and clinically meaningful antitumor activity in Japanese patients with R/R PMBCL, results that were consistent with those observed in prior global studies. Registry and the Registration No. of the study/trial: Clinicaltrials.gov: NCT04317066.

Practice Patterns and Incidence of Febrile Neutropenia in Patients Receiving Triplet Drug Chemotherapeutic Regimens in GUT Cancers: Do We Need to Add WBC Growth Factors? (ForGeT GCSF Study)

Background and Objectives: There are limited data on the requirement and duration of white blood cell (WBC) growth factor (GF) administration in patients receiving biweekly docetaxel, oxaliplatin, leucovorin, 5 Fluorouracil (mFLOT) or modified FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5 Fluorouracil (mFOLFIRINOX) regimens. Methods: The data of 749 patients with pancreatic, gastric, and colorectal adenocarcinomas treated with mFOLFIRINOX or mFLOT for at least three cycles between January 2018 and December 2022 were retrieved. Results: Of the 749 patients, 387 (52%) received mFLOT, while 362 (48%) received mFOLFIRINOX. Increased use of GF was seen in patients with diabetes mellitus (70 vs. 53%; p &lt; 0.001), prior chemotherapy (82 vs. 49%; p &lt; 0.001), prior pelvic radiotherapy (89 vs. 54%; p &lt; 0.001), prior surgery (70 vs. 49%; p &lt; 0.001), and stage I to III cancers as opposed to stage IV cancers (61 vs. 48%; p = 0.006). The use of GF resulted in a statistically lesser incidence of all-grades neutropenia (2.6 vs. 18.4%; p &lt; 0.001), grade 3/4 neutropenia (1.2 vs. 12.5%; p &lt; 0.001), and the primary endpoint of febrile neutropenia (FN; 1.2 vs. 6.1%; p = 0.001). There were no differences in the incidence of all grades of neutropenia (3.7 vs. 1.9%; p = 0.527), grade 3/4 neutropenia, and the primary endpoint of FN (1.2 vs. 1.1%; p = 0.079) in patients receiving single-day versus multiday GF, respectively. Interpretation and Conclusion: The use of GF reduces the rates of FN by approximately 80% in patients receiving mFLOT and mFOLFIRINOX, although incidences of FN are low with these regimens. The incidence of febrile neutropenia was similar with single-dose versus multiday GF in efficacy when administered with mFLOT and mFOLFIRINOX chemotherapy.

Sequential [177Lu]Lu-PSMA-617 and docetaxel versus docetaxel in patients with metastatic hormone-sensitive prostate cancer (UpFrontPSMA): a multicentre, open-label, randomised, phase 2 study

Lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 improves survival and quality of life in patients with metastatic castration-resistant prostate cancer, but whether it confers a benefit in hormone-sensitive disease is unknown. We aimed to evaluate [177Lu]Lu-PSMA-617 before docetaxel treatment in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer. UpFrontPSMA was an investigator-initiated, multicentre, open-label, randomised, phase 2 trial done at 11 Australian hospitals. Eligible patients had prostate adenocarcinoma without clinically significant neuroendocrine differentiation or small-cell histology, were aged 18 years or older, had less than 4 weeks on androgen deprivation therapy, had an Eastern Cooperative Oncology Group performance status of 0-2, and had high-volume PSMA-avid disease on [68Ga]Ga-PSMA-11 PET-CT with no major discordance on 2-[18F] fluorodeoxyglucose-PET-CT. Patients were randomly assigned (1:1) to the experimental treatment ([177Lu]Lu-PSMA-617 followed 6 weeks later by docetaxel) or standard-of-care treatment (docetaxel alone) using computer-based block randomisation with random block sizes, stratified by disease volume by conventional imaging and duration of androgen deprivation therapy at the time of registration. Neither patients nor investigators were masked to treatment assignment. Patients in the experimental group received two cycles of [177Lu]Lu-PSMA-617 7·5 GBq every 6 weeks intravenously, followed 6 weeks later by six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously, whereas patients in the standard-of-care treatment group received six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously. All patients received continuous androgen deprivation therapy. The primary endpoint was undetectable prostate-specific antigen (≤0·2 ng/mL) at 48 weeks, assessed using a modified intention-to-treat analysis. The trial is registered with ClinicalTrials.gov, NCT04343885. Between May 5, 2020, and April 18, 2023, 130 patients were randomly assigned, 63 (48%) to [177Lu]Lu-PSMA-617 plus docetaxel and 67 (52%) to docetaxel alone. All patients were male and no race or ethnicity data were collected. Median follow-up was 2·5 years (IQR 1·8-3·0). Four patients in the docetaxel alone group withdrew consent after randomisation and no data beyond screening were collected. An additional four patients were not evaluable for the primary endpoint at 48 weeks (two in each group). 25 (41%) of 61 patients (95% CI 30-54) in the [177Lu]Lu-PSMA-617 plus docetaxel group had undetectable PSA at 48 weeks compared with ten (16%) of 61 patients (9-28) in the docetaxel alone group (OR 3·88, 95% CI 1·61-9·38; p=0·0020). The most common grade 3 or 4 treatment-related adverse events were febrile neutropenia (seven [11%] of 63 patients in the [177Lu]Lu-PSMA-617 plus docetaxel group vs six [10%] of 63 patients in the docetaxel alone group) and diarrhoea (four [6%] of 63 patients vs none). Serious adverse events occurred in 16 (25%) patients in the [177Lu]Lu-PSMA-617 plus docetaxel group (none were definitely related to [177Lu]Lu-PSMA-617) and 16 (25%) patients in the docetaxel alone group. No treatment-related deaths occurred. [177Lu]Lu-PSMA-617 followed by docetaxel improved antitumour activity in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer compared with docetaxel alone, without increased toxic effects. Our data potentially support a role for [177Lu]Lu-PSMA-617 in metastatic hormone-sensitive prostate cancer. Prostate Cancer Research Alliance (Movember Foundation and Australian Government Medical Research Future Fund), US Department of Defence Impact Award-Clinical Trials, Endocyte/Advanced Accelerator Applications (a Novartis company), Australian Nuclear Science and Technology Organization, Victorian Cancer Agency, University of Melbourne, and Peter MacCallum Cancer Foundation.

The long-term impact of an antimicrobial stewardship program in febrile neutropenia: an 8 years follow up.

To describe the long-term effects of an ASP among febrile neutropenia (FN) patients. A quasi-experimental study was conducted between 2015 and 2023 at a tertiary care hospital in Istanbul, Türkiye. The ASP was implemented for FN patients, and the effects were assessed before and after the ASP interventions, which included FN clinical pathways and regular multi-disciplinary meetings with relevant healthcare workers. A total of 489 FN episodes of 290 patients were included, 42% were female, and the mean age was 56 years (SD: 15, range: 18-89 years). After the intervention, the rate of appropriate antimicrobial therapy at the levels of starting (p = 0.005), switching (p < 0.001), and de-escalation/discontinuation, (p < 0.001) significantly increased. Another positive impact of the ASP was a significant reduction in candidemia (from 4.88 to 0.74, p = 0.004), as well as a significant reduction in the 90-day mortality rate (from 19 to 5%, p < 0.001). In multivariate analysis, having a gram-negative bloodstream infection, prolonged days with fever, and a high risk for neutropenia were found to be significant predictors of 90-day mortality, while follow-up with ASP significantly reduced mortality. Implementation of ASP led to reduced candidemia and LOS without increasing mortality, even in a country with a high rate of antimicrobial resistance. Implementation of sustainable ASP for FN patients is critical in combating antimicrobial resistance.

Early Recognition of Drug-Induced Febrile Neutropenia Leads to an Improved Outcome in the Trauma Intensive Care Unit: A Case Report

AbstractTraumatic brain injury necessitates the use of antiepileptics for seizure prophylaxis, which are associated with multiple side effects including neutropenia, which may be dose dependent or idiosyncratic. We report the case of a young male with traumatic brain injury who developed febrile neutropenia, likely secondary to antiepileptic use. Early recognition and stopping of the drugs with use of granulocyte colony-stimulating factor led to the successful management of the patient.

Venetoclax Combined With FLAG-IDA in Refractory or Relapsed Acute Myeloid Leukemia.

The prognosis of patients with refractory or relapsed AML (R/R-AML) is very limited. To (re)achieve complete remission, there has recently been increasing evidence that the combination of venetoclax (VEN) with chemotherapy is associated with improved outcomes. Our retrospective, single-center study of 53 R/R-AML patients with a median follow-up time of 11.0 months compared standard salvage chemotherapy (FLAG-Ida or HAM in n = 35 patients) with a combination of venetoclax (VEN) and FLAG-Ida (FLAVIDA in n = 18 patients) concerning safety and efficacy. Regarding the primary endpoints, there was a statistically significant increased eventfree survival (EFS) in the FLAVIDA group compared to patients with standard chemotherapy based on the univariate log-rank-test and in the multivariate Cox regression analysis (HR 0.22 [95% CI 0.05, 0.97]). There were no differences between the two groups in terms of patients developing febrile neutropenia CTCAE III° and IV° or a delay in hematological recovery. In addition, a clear trend towards an improved overall response rate (78% vs. 51%) was demonstrated in the FLAVIDA group. The FLAVIDA regimen represents a promising treatment alternative for R/R AML patients with a high response rate and significantly improved EFS compared to standard chemotherapy.

Predicting Neutropenic Sepsis in Patients with Hematologic Malignancy: A Retrospective Case-Control Study.

Neutropenic sepsis (NS) is one of the leading causes of death among patients with hematologic malignancies. Identifying its predictive factors is fundamental for early detection. Few studies have evaluated the predictive factors in relation to microbial infection confirmation, which is clinically important for initiating sepsis treatment. This study aimed to determine whether selected biomarkers (i.e., body temperature, C-reactive protein, albumin, procalcitonin), treatment-related characteristics (i.e., diagnosis, duration of neutropenia, treatment modality), and infection-related characteristics (i.e., infection source, causative organisms) can predict NS in patients with hematologic malignancies. We also aimed to identify the optimal predictive cutoff points for these parameters. This retrospective case-control study used the data from a total of 163 patients (58 in the sepsis group and 105 in the non-sepsis group). We collected data with reference to the day of specimen collection, with which microbial infection was confirmed. Multiple logistic regression was used to determine predictive risk factors and the area under the curve (AUC) of the receiver operating characteristic for the optimal predictive cutoff points. The independent predictors of NS were average body temperature during a fever episode and procalcitonin level. The odds for NS rose by 9.97 times with every 1°C rise in average body temperature (95% confidence interval, CI [1.33, 75.05]) and by 2.09 times with every 1 ng/mL rise in the procalcitonin level (95% CI [1.08, 4.04]). Average body temperature (AUC = 0.77, 95% CI [0.68, 0.87]) and procalcitonin levels (AUC = 0.71, 95% CI [0.59, 0.84]) have fair accuracy for predicting NS, with the optimal cutoff points of 37.9°C and 0.55 ng/mL, respectively. This study found that average body temperature during a fever episode and procalcitonin are useful in predicting NS. Thus, nurses should carefully monitor body temperature and procalcitonin levels in patients with hematologic malignancies to detect the onset of NS.

Use of EMPAgliflozin in the prevention of CARDiotoxicity: the EMPACARD – PILOT trial

BackgroundAnthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10–15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatmentMethodsThe EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections.ResultsDuring the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04–0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure.ConclusionEmpagliflozin is associated with reduced incidence of CTRCD in high-risk patients treated with anthracyclines. These data should serve as the foundation for a clinical trial to test whether SGLT2 inhibitors can reduce the incidence of heart failure in this patient group.

Carboplatin and Paclitaxel Chemoradiation for Localized Anal Cancer in Patients Not Eligible for Mitomycin and 5-Fluorouracil.

Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Ten patients were included; eight were female, and the median age was 75.5 years (54-87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40-100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4-50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials.

A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units

Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value. Method We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection. Results A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for &gt;5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p&lt;0.04) Conclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.

An Institutional Febrile Neutropenia Protocol Improved the Antibacterial Treatment and Encouraged the Development of a Computerized Clinical Decision Support System.

We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline's release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.

Preadmission Penicillin Allergy Evaluation Before Hematopoietic Stem Cell Transplantation Optimizes Febrile Neutropenia Treatment and Inpatient Resource Utilization

Febrile neutropenia is a common complication of conditioning chemotherapy for hematopoietic stem cell transplant (HSCT), but a major barrier for optimal treatment of febrile neutropenia is historical penicillin allergies. Our group recently published a development of a clinical pipeline for delabeling penicillin allergies in adult patients planned to undergo hematopoietic stem cell transplant (HSCT). In this retrospective cohort study, we followed patients to evaluate their outcomes during inpatient admission for HSCT. We hypothesized that, among patients planned for HSCT with a self-reported penicillin allergy, completing penicillin allergy testing (amoxicillin ingestion challenge with or without concomitant penicillin skin testing) prior to HSCT admission would be associated with differences in inpatient treatment for febrile neutropenia (including antibiotic selection and timing of antibiotic administration) and improved inpatient resource utilization (including nursing and inpatient physician consults). We identified patients with a self-reported penicillin allergy who answered a penicillin allergy questionnaire and were subsequently admitted to our institution for HSCT. We divided the cohort into 2 groups: patients whose penicillin allergy was evaluated prior to admission (EPTA) and patients whose penicillin allergy was not evaluated prior to admission (NEPTA). We then performed comparison between the 2 groups for general clinical outcomes of HSCT admission (duration of admission, need for ICU transfer, readmission rate, etc.), febrile neutropenia treatment, and inpatient resource utilization. Statistics were calculated using the non-parametric two-tailed Fisher exact test for categorical outcomes and the non-parametric two-tailed Mann-Whitney U test for numerical outcomes RESULTS: Within our cohort, 35 patients completed penicillin allergy testing prior to HSCT admission (EPTA) and 44 patients did not (NEPTA). Demographics were similar between these groups, and there was no significant difference in the rate of febrile neutropenia during HSCT admission (EPTA 64% vs NEPTA 66%, p=1.00). EPTA patients were significantly more likely to receive standard first-line antibiotics (cefepime or ceftazidime) for febrile neutropenia (EPTA 95% vs NEPTA 65%, p=0.015) and time between febrile neutropenia onset and antibiotic administration was shorter (EPTA mean 66 mins vs NEPTA mean 121 mins, p=0.0058). No patients in the EPTA group experienced an immediate hypersensitivity reaction (hives, anaphylaxis, etc.) or severe cutaneous adverse reaction (SCAR) during HSCT admission. EPTA patients were also significantly less likely to require 1:1 nursing for antibiotic test doses, challenges, and desensitizations (EPTA 0% vs NEPTA 49%, p<0.0001); less likely to require inpatient allergy consult (EPTA 0% vs NEPTA 12%, p=0.031); and less likely to require inpatient antimicrobial stewardship consult (EPTA 0% vs NEPTA 13%, p=0.013) during their HSCT admission. In summary, patients who completed penicillin allergy testing prior to HSCT admission were more likely to receive first-line antibiotics and received antibiotics more rapidly for treatment of febrile neutropenia. Furthermore, patients who completed penicillin allergy testing prior to HSCT admission were less likely to require 1:1 nursing, inpatient allergy consults, and inpatient antimicrobial stewardship consults during HSCT admission.