Episodes Of Febrile Neutropenia Research Articles

ORAL MICROBIOME SEQUENCING TEST IN A CLINICAL CASE OF ACUTE MYELOID LEUKEMIA WITH PERSISTENT ORAL INFECTION

A previously healthy, 45-year-old female patient, with the recurrence of acute myeloid leukemia, was hospitalized for oncological treatment. During hospitalization, she presented episodes of febrile neutropenia associated with pharyngotonsillitis and thrombocytopenia. Oral clinical examination presented erythematous and swollen gums with active bleeding. Thus, mechanical and chemical local control of the oral microbiota and systemic antibiotic therapy were instituted. Three conclusive cultures of gingival secretion were performed, which was conclusive for normal oropharyngeal microbiota; however, the infection panorama is still persistent. An oral microbiome DNA from saliva test was performed, resulting in 167027 sequences harboring 34 types of bacteria. Among the identified microorganisms, Granulicatella adiacens and Veillonella parvula were found in greater quantity, which could be responsible for oral homeostasis instability. Two days after the oral microbiome test result, the patient died. A previously healthy, 45-year-old female patient, with the recurrence of acute myeloid leukemia, was hospitalized for oncological treatment. During hospitalization, she presented episodes of febrile neutropenia associated with pharyngotonsillitis and thrombocytopenia. Oral clinical examination presented erythematous and swollen gums with active bleeding. Thus, mechanical and chemical local control of the oral microbiota and systemic antibiotic therapy were instituted. Three conclusive cultures of gingival secretion were performed, which was conclusive for normal oropharyngeal microbiota; however, the infection panorama is still persistent. An oral microbiome DNA from saliva test was performed, resulting in 167027 sequences harboring 34 types of bacteria. Among the identified microorganisms, Granulicatella adiacens and Veillonella parvula were found in greater quantity, which could be responsible for oral homeostasis instability. Two days after the oral microbiome test result, the patient died.

Prolonged 14-day continuous infusion of high-dose ifosfamide (14IFO) for relapsed/refractory high-grade osteosarcoma (R/R HOS): A retrospective multicenter cohort study.

11534 Background: The prognosis of patients (pts) with relapsed/refractory (R/R) High-Grade Osteosarcoma (HOS) remains dismal without an agreement on systemic therapy. The use of 14IFO with an external pump in outpatient setting (1g/sqm/day x 14 days every 21) in R/R HOS pts is limited. This is the first retrospective cohort study focused on 14IFO activity and toxicity in this setting (NCT04651569). Methods: Five Centers of the Italian Association of Pediatric Onco-Hematology and Italian Sarcoma Group participated to the study. Primary aim is to investigate 14IFO activity in pts with R/R HOS younger than 40 years. Secondary aim is to evaluate toxicity, according to CTCAE v.5, and clinical benefit. Progression Free Survival (PFS) and Overall Survival (OS) analysis are performed using the Kaplan Meier method with 95% confidence interval (CI). Results: Between 2012 and 2021, 26 R/R HOS pts were treated with 14IFO (median follow-up: 17,5 months, range: 4,6 – 83 months). Median age is 19 years at the beginning of 14IFO; eleven pts (42%) are ≤ 18 years. Three pts (12%) have a localized HOS, twelve pts (46%) have pulmonary disease only and eleven pts (42%) have a pluri-metastatic HOS. Eleven pts (42%) have a relapsed HOS with a median disease-free interval (DFI) of 13 months before 14IFO, the remaining (58%) have a refractory disease to two or more treatments. Overall, thirteen pts (50%) receive 14IFO as second line therapy and fifteen pts (57%) are pre-treated with Ifosfamide in first line. Disease Control Rate is 57,5% (5 Partial Response + 10 Stable Disease). Seven pts (27%) receive a local treatment after 14IFO (5 surgery, 1 Radiotherapy (Rt), 1 Carbon Ion Rt). The median PFS is 4,1 months (95% CI 2.13, 7.37). 6-month and 1-year PFS are 38% (95% CI 24-63) and 8% (95% CI 2-29), respectively. The median OS is 13.7 months (95% CI 10.6 – 23.7). 1-year and 2-year OS are 51% (95% CI 35-75) and 22% (95% CI 9.5-49), respectively. Relapsed pts have both longer median PFS and OS compared to pts with a refractory disease [PFS: 7.33 months vs 2.13 months (p = 0.02); OS: 19.4 months vs 10.7 months (p = 0.1)]. Sixteen pts (61%) receive at least 4 cycles and an amount of 101 cycles are evaluated for toxicity. Grade 4 hematological toxicity is reported in 15 cycles (14,8%) as follows: i) white-blood cell decrease in 6 cycles (6%); ii) neutropenia in 7 cycles (7%); iii) thrombocytopenia in 2 cycles (2%). One patient has one episode of febrile neutropenia. No grade 3-4 non hematological toxicities are reported. Conclusions: This trial shows a non inferiority activity of 14IFO compared to other treatments in this setting, despite the small number of pts. Therefore, 14IFO should be considered as a treatment option in R/R HOS, especially for its well tolerated toxicity profile and the home-administration that improve patient’s quality of life and it could significantly reduce cancer care cost. Clinical trial information: NCT04651569 .

Enzalutamide, docetaxel and androgen deprivation (ENZADA trial) for metastatic castrate sensitive prostate cancer (mCSPC).

5072 Background: The use of contemporary androgen receptor signaling inhibitors (ARSI) in combination with docetaxel (Doc) and androgen deprivation therapy (ADT) has shown improved outcomes in recent trials. Prostate specific antigen (PSA) serologic complete response (CR) has correlated with improved overall survival (OS) in prior studies. In the E3805 study, the 12-month PSA CR rate was 28% for the ADT + Doc arm. In this study, we hypothesized the combination of androgen deprivation therapy with Doc and enzalutamide (Enz) would improve the 52-week PSA CR rate compared to the historical control with ADT + Doc in newly diagnosed patients with mCSPC. Methods: The ENZADA trial is a single institution phase II study in patients with mCSPC. Patients received ADT, Doc 75 mg/m2 IV every 3 weeks for up to 6 cycles and Enz 160mg daily until radiographic progression. The primary endpoint was 52-week PSA CR. Secondary endpoints included safety/toxicity, best PSA response, time to castration resistance (TTCR) and overall survival (OS). Patients were stratified by radiographic volume of disease by E3805 criteria. The study was designed with 90% power and 1-sided alpha 0.1 to show an improvement in the 52-week PSA CR from 25% to 45%, with rejection of the null hypothesis if 14 of 39 evaluable subjects achieved a 52-week PSA CR. Results: Between Sep 2017 and Aug 2021, 40 subjects were enrolled, and 36 were evaluable for the primary endpoint. At the data cut-off of 9/2/22, median follow up was 42.6 months. Thirty subjects (75%) had high volume disease, and 32 (80%) subjects presented with de novo metastatic disease. Median age was 64.5 years; 65% (N=26) were identified as White and 35% (N=14) were identified as Black or African American (AA). Median pretreatment PSA was 129.5 ng/ml. 67.5% (27/40) of subjects received six cycles of Doc. 10% (4/40) of subjects had Enz dose modifications. 52-week PSA CR occurred in 22/36 (61.1%) patients (P<0.001). 13/23 (56.5%) White subjects and 9/13 (69.2%) Black or African American subjects experienced 52-week PSA CR (P=.50). Median TTCR was not reached; castrate resistance at 2 and 4 years was 62.4% and 53.5%, respectively. Eleven deaths occurred (3/14 Black or AA and 8/26 White); median OS was not reached. OS at 2 and 4 years was 83.2% and 63.1%, respectively. OS at 2 and 4 years was 85.7% and 78.6%, respectively, in Black or AA subjects and 82.4% and 50.9%, respectively, in White subjects (P=.26). Treatment-related Grade 3-5 adverse events occurred in 17/40 (42.5%) patients, including 3 episodes of febrile neutropenia. Conclusions: ADT+Doc+Enz improved 52-week PSA CR compared to historical control with ADT+Doc. These results are consistent with the recent ARASENS and PEACE1 studies and support the use of triplicate regimens combining ADT+Doc+ARSI in newly diagnosed mCSPC patients. No detectable difference in outcome by race has been observed to date in the study cohort. Clinical trial information: NCT03246347 .

Evaluation of FTO polymorphism in 6-mercaptopurine related intolerance in children with acute lymphoblastic leukemia.

Thiopurine drugs like 6-Mercaptopurine (6MP) are the cornerstone of maintenance therapy in acute lymphoblastic leukemia (ALL). A recently described variant in alpha-ketoglutarate dependent dioxygenase (FTO) gene has been reported to play an important role in thiopurine induced myelosuppression. In this study, we genotyped a coding variant (p.Ala134Thr, rs79206939) and an intronic variant (rs16952570) of FTO in 174 Indian children (age ≤ 12years) with ALL on maintenance phase of chemotherapy and examined correlation with the risk of thiopurine induced myelosuppression and hepatic toxicity. The prevalence of FTO-rs16952570 polymorphism was 18.4% (32/174) with 142 (82%) cases having TT genotype, 26 (15%) cases with TC genotype and 6 (3.4%) cases having CC genotype. FTO-rs79206939 was absent and non-polymorphic in our study group. The mean dose of 6-MP during 36weeks of maintenance of TT, TC and CC carriers of FTO-rs16952570 was 53.7, 53.6 and 54.1mg/m2/day. Number of patients tolerating starting dose of 60mg/m2/day was significantly higher in CC (50%) than TT/TC (14%) genotype carrying cases (p = 0.014). However, no statistical significance was observed for total leukocyte count (TLC), absolute neutrophil count (ANC) as well as for platelets counts in patients harboring FTO-rs16952570 TT/TC/CC genotype at 4, 8, 12, 24 and 36weeks after start of thiopurine therapy. Further, no significant correlation was noted between number of weeks of chemotherapy interruptions or episodes of febrile neutropenia and no evidence of hepatotoxicity was found with the genotype studied. Polymorphism in FTO-rs16952570 did not show any correlation with thiopurine related toxicity in ALL patients.

Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP)

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient’s characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance.The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends.

D-index and invasive fungal infections (IFIs) in adult acute myeloid leukemia (AML) patients with the first episode of febrile neutropenia.

This study aimed to evaluate the performance of the D-index, a calculated measure of neutropenic burden, in predicting the risk of invasive fungal infections (IFIs) in acute myeloid leukemia (AML) patients. A retrospective study of adult AML patients who received the first induction chemotherapy and developed febrile neutropenia was conducted. Clinical characteristics, laboratory data, and the calculation of the D-index and cumulative D-index (c-D-index) were collected and analyzed between patients with and without IFIs. A total of 101 patients were included, with 16 (15.8%) patients who developed IFIs. Clinical characteristics, antifungal prophylaxis, and AML cytogenetic risk were similar between patients with or without IFIs. The results showed that the D-index and c-D-index were more effective in predicting IFIs than the duration of neutropenia. With the D-index cutoff of 7083, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.3%, 83.5%, 48.2%, and 95.9%, respectively. c-D-index at 5625 revealed sensitivity, specificity, PPV, and NPV for IFIs of 68.8%, 68.2%, 28.9%, and 92.1%, respectively. Using this cutoff of c-D-index, patients without IFIs were overtreated with an antifungal regimen in 45 (52.9%) cases. The D-index and c-D-index were helpful indicators for defining the risk of IFIs in AML patients with febrile neutropenia.

Value-Based Care for Healthy Children With First Episode of Febrile Neutropenia.

There is a lack of guidance on the management of febrile neutropenia in otherwise healthy children, including the need for hospitalization and antibiotic administration, leading to significant practice variation in management. The aim of this initiative was to decrease the number of unnecessary hospitalizations and empirical antibiotics prescribed by 50% over a 24-month period for well-appearing, previously healthy patients older than 6 months presenting to the emergency department with a first episode of febrile neutropenia. A multidisciplinary team of stakeholders was assembled to develop a multipronged intervention strategy using the Model for Improvement. A guideline for the management of healthy children with febrile neutropenia was created, coupled with education, targeted audit and feedback, and reminders. Statistical control process methods were used to analyze the primary outcome of the percentage of low-risk patients receiving empirical antibiotics and/or hospitalization. Balancing measures included missed serious bacterial infection, emergency department (ED) return visit, and a new hematologic diagnosis. Over the 44-month study period, the mean percentage of low-risk patients hospitalized and/or who received antibiotics decreased from 73.3% to 12.9%. Importantly, there were no missed serious bacterial infections, no new hematologic diagnoses after ED discharge, and only 2 ED return visits within 72 hours without adverse outcomes. A guideline for the standardized management of febrile neutropenia in low-risk patients increases value-based care through reduced hospitalizations and antibiotics. Education, targeted audit and feedback, and reminders supported sustainability of these improvements.

Documento de consenso de manejo de neutropenia febril en el paciente pediátrico oncohematológico de la Sociedad Española de Infectología Pediátrica (SEIP) y la Sociedad Española de Hematología y Oncología Pediátrica (SEHOP)

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance.The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends.

Cyclic neutropenia and concomitant IgA nephropathy: a case report

BackgroundIgA nephropathy (IgAN) is universally recognized as one of the most common primary glomerular diseases in all ages. Cyclic neutropenia (CN) is a rare haematologic disorder that is associated with mutations of the ELANE gene. The co-occurrence of IgAN and CN is extremely rare. This is the first case report of a patient with IgAN and genetically confirmed CN.Case presentationWe report a case of a 10-year-old boy who presented with recurrent viral upper respiratory tract infections accompanied by several episodes of febrile neutropenia, haematuria, proteinuria and acute kidney injury. Upon first admission, his physical examination was unremarkable. His kidney function was impaired, whereas his urine microscopy showed evidence of macroscopic haematuria and proteinuria. Further workup showed elevated IgA. The renal histology was consistent with mesangial and endocapillary hypercellularity with mild crescentic lesions, while immunofluorescence microscopy showed IgA-positive staining, which was characteristic of IgAN. Moreover, genetic testing confirmed the clinical diagnosis of CN, therefore Granulocyte colony-stimulating factor (G-CSF) was initiated to stabilize the neutrophil count. Regarding proteinuria control, the patient was initially treated with an Angiotensin-converting-enzyme inhibitor for approximately 28 months. However, due to progressive proteinuria (> 1 g/24 h), Corticosteroids (CS) were added for a period of 6 months according to the revised 2021 KDIGO guidelines with favorable outcome.ConclusionsPatients with CN are more susceptible to recurrent viral infections, which can trigger IgAN attacks. In our case CS induced remarkable proteinuria remission. The use of G-CSF contributed to the resolution of severe neutropenic episodes, viral infections and concomitant AKI episodes, contributing to better prognosis of IgAN. Further studies are mandatory to determine whether there is a genetical predisposition for IgAN in children with CN.

Mild COVID-19 outcomes in adults with inborn errors of immunity: a single-center experience

Currently, 640 million cases of coronavirus disease 2019 (COVID-19) and 6.6 million deaths have been reported world-wide. Risk factors for severe COVID-19 are known, including those with compromised immunity. Among patients with inborn errors of immunity (IEI), early reports of severe outcomes lead to strict masking and social distancing measures. While this resulted in relatively low infection rates among those with IEI, real-world data describing the clinical course of COVID-19 in this patient population have remained limited. We performed a retrospective study of adult IEI patients followed by our center in which a positive test (rapid antigen or PCR) for COVID-19 was determined between November 2021-November 2022. Medical charts were reviewed, and patient interviews conducted. All patients provided informed consent. Twenty-nine patients were enrolled (22 females, 7 males), aged between 18–69 years (median: 20–29 years). The cohort included those with antibody deficiencies (41.37%), combined immunodeficiencies (34.48%; HIES, CARD11, STAT1-GOF), immune dysregulation disorders (20.69%; LRBA deficiency, AIRE deficiency) and phagocyte defect (3.45%; CGD). The duration of symptoms ranged between 3 days-4 weeks (median: < 1 week). Upper respiratory symptoms (including sore throat, congestion) were reported in 97% while fever was present in 41% of patients. Prior to infection, 14 (48%) patients had underlying asthma or bronchiectasis - 2 subsequently experienced shortness of breath and were treated with inhalers or Sotrovimab, respectively. No treatment was required in 65.5% of cases. The remaining received Paxlovid (10.3%), Sotrovimab (13.79%), or antibiotics (10.3%). Of the 2 patients with STAT1-GOF, one tested positive during a repeat episode of febrile neutropenia which required hospitalization. No other patients were hospitalized or needed ICU admission. No deaths were recorded. In light of these favourable outcomes, patients with IEI can gradually and safely return to normal activities.

Evaluation of a safe neutrophil count for cessation of intravenous antibiotics and early hospital discharge in stable, afebrile patients recovering after acute myeloid leukemia therapy or an autograft

Currently there are no guidelines on a safe neutrophil count(ANC) for intravenous antibiotic(IVAB) cessation and hospital discharge in patients recovering after febrile neutropenia(FN). We assessed the safety in selected patients after recent FN of prompt IVAB cessation and hospital discharge. Safety was defined as no fever recurrence after IVAB cessation and readmission in the 10-days post-discharge for infections. A retrospective, single center audit conducted on 92 adult hematology patients admitted with de novo acute myeloid leukemia (AML) for intensive chemotherapy or for an autograft. Most admissions (n = 128/141;91%) were complicated by FN. Half of FN episodes ceased IVAB promptly with a median(range) ANC of 0.6(0.1–4.9x109/L); none of these episodes had recurrent fever requiring IVAB resumption. Prompt discharge occurred in 45% overall. Subsequent unplanned readmission rates were low. In afebrile, stable AML and autograft patients without medico-social barriers to discharge, IVAB can be ceased and hospital discharges safely done ≤24h of ANC ≥ 0.2x109/L.

The role of presepsin in pediatric patients with oncological and hematological diseases experiencing febrile neutropenia

Febrile neutropenia (FN) represents one of the main complications of pediatric patients with oncological and hematological diseases. In these patients, it is crucial to identify bacterial infections. The aim of this study is to evaluate presepsin as an early biomarker of bacterial infections during FN. We compared patients with oncological and hematological diseases and a 2:1 age-matched healthy control group. In the FN group, we evaluated 4 biomarkers, namely, C reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL6) and presepsin at the onset of fever (T0) and 48 h after T0 (T1). In the control group, we only evaluated presepsin. We enrolled a total of 41 children with oncological and hematological diseases disease experiencing 50 FN episodes and 100 healthy patients in the control group. In patients with FN, we found that presepsin was significantly higher than in the control group (p < 0.001). However, in the FN group, we did not find a statistically significant difference between patients with and without bacteremia (p = 0.989 at T0, p = 0.619 at T1). Presepsin values at T1 were higher in patients experiencing an unfavorable outcome (p = 0.025). This study shows that presepsin increases in neutropenic patients, but it only revealed useful in predicting an unfavorable outcome 48 h from the onset of fever.

High frequency of viridians group streptococci bacteremia in pediatric neuroblastoma high-risk patients during induction chemotherapy

Existing literature on febrile neutropenia (FN) has categorized patients with acute leukemia or those undergoing allogeneic stem cell transplantation (SCT) as being high risk for severe infection, bacteremia, and poor outcomes. Comprehensive studies of infection risk in pediatric high-risk neuroblastoma (NB-HR) during induction chemotherapy are limited, and mostly merged within the solid tumor (ST) group. Therefore, it is unclear whether infectious complications and outcomes for NB-HR are the same as in other ST groups. We conducted a retrospective medical record review of pediatric FN patients in a single center from March 2009 to December 2016. FN episodes were categorized into five groups based on underlying diagnosis (acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), NB-HR during induction chemotherapy, other solid tumors, and SCT). Comparative analyses of infectious complications between patients with NB-HR and those with other types of cancer diagnoses were performed. A total of 667 FN episodes (FNEs) were identified in 230 patients. FNEs occurred in 82 episodes with NB-HR. Bloodstream infection (BSI) occurred in 145 (21.7%) of total FN episodes. The most isolated organisms were the viridians group streptococci (VGS) (25%). NB-HR patients have higher rates of VGS bacteremia (OR 0.15, 95% [CI 0.04, 0.56]) and are more likely to be admitted to the Pediatric Intensive Care Unit (PICU) compared to patients with other solid tumors (OR 0.36, 95% [CI 0.15, 0.84]). Interestingly, there is no difference in VGS rates between patients with NB-HR and those with AML despite the fact that NB-HR patients do not receive a cytosine arabinoside (AraC)-based regimen. This large neuroblastoma cohort showed that patients with NB-HR during induction chemotherapy are at higher risk for VGS bacteremia and PICU admissions compared with patients with other solid tumors. Further prospective studies are needed to investigate infection-related complications in this high-risk group and to improve morbidity and mortality.

Impact of Adding a Rapid PCR-Based Blood Culture Identification Panel to the Antimicrobial Stewardship Program of Patients with Febrile Neutropenia in a Peruvian Referral Hospital.

The addition of Biofire® FilmArray® Blood Culture Identification panel 2 (BCID2) to the antimicrobial stewardship program (ASP) could improve outcomes in bloodstream infections (BSI) of patients with febrile neutropenia (FN). A pre- and post-quasi-experimental single-center study was conducted at a reference hospital in Peru. Three groups were considered: patients with BSI before ASP intervention (control group), patients with BSI after ASP intervention (group 1), and patients with BSI after ASP intervention plus BCID2 PCR Panel implementation (group 2). Overall, 93 patients were identified (32 control, 30 group 1, 31 group 2). The median time to effective therapy was significantly shorter in group 2 compared to group 1 and control group, respectively (3.75 vs. 10 h, p = 0.004; 3.75 vs. 19 h, p < 0.001). No significant differences in terms of relapse of bacteremia, in-hospital mortality (all cause), and 30-day-all-cause hospital readmission between the three study periods were found. The appropriateness of empirical antimicrobial use, adding or change, and the following de-escalation or discontinuation was significant when the two intervention periods were compared with the control group (p < 0.001). In addition to the lack of local studies documenting the microbiological profile of FN episodes, adding syndromic panels-based testing could allow for the consolidation of ASP strategies.

Çocukluk çağı febril nötropenisinde solunum virüsü panelinin maliyet etkinliği

ABSTRACT&#x0D; Objective: The aim of this study is to analyze the clinical utility and cost of the respiratory virus panel test in the febrile neutropenia (FN) episode in children undergoing chemotherapy.&#x0D; Material and Method: From 2014 to 2018, 180 episodes of FN in 93 children with cancer were retrospectively analyzed. The patients were divided into those with (Group A) and without respiratory virus panel (Group B). The demographic and clinical features and cost analysis of the groups A and B were noted.&#x0D; Results: Of these FN episodes, 46 were in Group A (25.5%) and 134 were in Group B (74.5%). We found positivity in 45 (97.8%) of 46 episodes in Group A. While modification was required in 14 FN episodes (30.4%) in Group A, modification was required in 35 FN episodes (26.1%) in group B. The difference was not statistically significant (p=0.570). In Group A, only 5 (10.8%) were modified according to the respiratory virus panel. The respiratory virus panel prices were $72.43 (interquartile range, $38.8). The ratio of respiratory virus panel cost to the total cost was 9.67% (interquartile range 11.6). The median total cost of group A was $663.18 (interquartile range, 850.1), while that of group B was $596.24 (interquartile range, 723.81). The difference was not statistically significant (p=0.141).&#x0D; Conclusion: The respiratory virus panel may contribute to the preference of antibiotics by giving rapid results in FN attacks. However, no effect on modification rates was observed, and only a small percentage of patients underwent antibiotic modification according to respiratory virus panel.

Risk factors and predictors of adverse outcomes of in paediatric febrile neutropenia

Background: Febrile neutropenia (FN) is the commonest acute complication of cancer treatment in children. The identification of patients at risk for FN as well as adverse outcomes has been described.Aim: To evaluate the prevalence and potential risk factors for FN and describe adverse outcomes in a cohort of children treated for cancer.Setting: The study was carried out in a paediatric oncology unit in a children’s hospital, Cape Town, South Africa.Methods: A retrospective study from 01 January 2017 to 31 December 2019 on children with cancer at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa.Results: Two hundred and sixty-seven episodes of FN occurred in 179 patients. Independent predictors of FN were acute myeloid leukaemia (AML) (p = 0.039), acute lymphocytic leukaemia (ALL) (p = 0.020) and intensive chemotherapy (p ≤ 0.001). Mucositis (p = 0.001), central venous access device (CVAD) placement (p = 0.004), haematologic malignancies (p = 0.040), blood transfusion during FN episode (p 0.001) and severe neutropenia (white cell counts 0.3 × 109 cells/L) (p ≤ 0.001) were risk factors for adverse outcomes. The mortality rate from FN was 3.57%. Independent predictors of adverse outcomes in those with FN were AML (p = 0.001), CVAD placement (p = 0.019) and severe neutropenia (p = 0.005).Conclusion: Treatment related adverse outcomes following chemotherapy-induced FN are likely in children with AML, severe neutropenia and with CVAD placement.Contribution: Adverse outcomes from paediatric febrile neutropenia is high. There is need for clinical decision making aimed at prevention and early identification of individuals at risk.

Lower Respiratory Infections in Children With Febrile Neutropenic Leukemia: A Case in a Jordanian Hospital.

The study aimed to examine the prevalence of pneumonia in pediatric children diagnosed with leukemia at King Hussein Medical Center, Royal Medical Services, Amman, Jordan. The study was conducted from January 2019 to March 2020. A total of 100 hospitalized leukemia patients with febrile neutropenic episodes were evaluated for the presence of pneumonia. Samples were collected from all patients and tested for microbial growth. Univariate analysis revealed that age (P = .033) and packed cell volume (P = .006) were statistically significant risk factors, associated with the prevalence of pneumonia in leukemia patients with febrile neutropenia episodes. Similarly, as the absolute neutrophil count counts increased with an odds ratio and a 95% confidence interval of 2.386 (0.859-6.625), the odds of pneumonia in febrile neutropenic patients were more prevalent. The study reported the prevalence of pneumonia in immunocompromised febrile neutropenic patients with leukemia, which could lead to the development of evidence-based febrile neutropenic treatment protocol development. It will assure more responsive patient management and treatment.

Abstract P4-01-28: PALBOSPAIN: OBSERVATIONAL ANALYSIS OF FIRST-LINE THERAPY WITH PALBOCICLIB IN PATIENTS WITH HR+/HER2- METASTATIC BREAST CANCER (MBC) IN REAL-LIFE CONDITIONS

Abstract INTRODUCTION AND OBJECTIVES Palbociclib associated with hormone therapy (HT) has shown significant benefit in progression-free survival (PFS) and response rate versus HT alone in patients with HR+, HER2- MBC. The PALBOSPAIN study evaluates the efficacy and safety of palbociclib treatment under real-life conditions. The main objective of the study was to assess PFS, and secondary objectives were overall survival (OS), response rate, time to next line of treatment, percentage of dose reduction and safety. MATERIAL AND METHODS This is an observational, ambispective, multicenter, nation-wide study. Patients diagnosed with HR+/HER2- MBC who had started first-line treatment with palbociclib between November 2017 and November 2019 were included. Patients treated within a clinical trial were excluded, as were those who had received any previous systemic treatment for advanced disease. RESULTS 762 patients from 35 centers were included. 79% (n=600) were postmenopausal, 54.9% (n=418) had visceral disease, and 30.6% (n=233) had de-novo metastatic disease. Palbocliclib was combined with an aromatase inhibitor in 69.6% of patients and fulvestrant in 30.2% Four groups were established to assess efficacy (table 1): overall population; patients with de-novo metastatic disease (cohort A); patients relapsing &amp;gt;12 months after the end of adjuvant hormonal therapy (cohort B); and patients relapsing within 12 months after the end of adjuvant hormonal therapy (cohort C). Median PFS was 24 months (CI 95%; 25-27) overall and 28 (IC 95%; 23-39), 29 (IC 95%;25-35) and 14 months (IC 95%;11-17) for cohorts a, B and C, respectively. Median overall survival was 42 months (40-NA). The most common side effects were neutropenia (71.3%, grade 3-4 in 52.5%, no episodes of febrile neutropenia), fatigue (38.6%), leucopenia (29.8%), anemia (28.9%), articular pain (19%), and thrombocytopenia (2,2%). 49% (n=385) of patients required dose reduction of palbociclib (one level in 27.6% and two levels in 21.4%). CONCLUSION In the first two years after its approval in Spain, palbociclib in first line of HR+/HER2- MBC in real-life conditions yielded PFS and safety results comparable to those of PALOMA 2 and PALOMA 3 clinical trials. OS results were poorer, although the population included in this retrospective study is heterogeneous and median survival values have not been reached in some subgroups. Table 1. Efficay results of palbociclib in real world Citation Format: Noelia Martínez-Jáñez, Meritxell Bellet Ezquerra, Fernando Henao, Luis Manso, Antonio Antón, Pilar Zamora, Serafin Morales Murillo, Pablo Tolosa, Raquel Andrés, Lourdes Calvo, Elena Galve, Rafael Lopez, Francisco Ayala de la Peña, Sara López-Tarruella, Laia Boronat, Tamara Martos, J. Ignacio Chacón, Isabel Álvarez, Juan de la Haba-Rodríguez, Fernando Moreno Antón. PALBOSPAIN: OBSERVATIONAL ANALYSIS OF FIRST-LINE THERAPY WITH PALBOCICLIB IN PATIENTS WITH HR+/HER2- METASTATIC BREAST CANCER (MBC) IN REAL-LIFE CONDITIONS [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-28.

MANAGEMENT OF FEBRILE NEUTROPENIA IN LUNG CANCER

Febrile neutropenia (FN) is defined as an oral temperature of &gt;38.3° C or two consecutive measures &gt; 38° C within 2 hours accompanied by an absolute neutrophil count (ANC) of 500/L or a predicted decrease below 500/L in individuals undergoing systemic chemotherapy for cancer. FN is one of the oncological emergencies that can influence cancer patients' outcomes since it can increase morbidity, treatment delays, decreased survival, and expanded costs. The incidence of FN is 3.7-28% in lung cancer patients. Mortality associated with FN episodes is 15%. FN risk factors include chemotherapy regimen, age, comorbidities, mucositis, performance status, and previous FN history. Validated predicted instruments such as The Multinational Association for Supportive Care in Cancer (MASCC) or The Clinical Index of Stable Febrile Neutropenia (CISNE) score could assist in risk assessment of FN and determine advanced management. Effective therapy of FN requires investigation of diagnosis as soon as possible and acknowledging the potential source of infection. The prophylactic granulocyte colony-stimulating factors (G-CSF) and anti-microbials successfully reduced mortality due to FN.

The efficacy and toxicity of dexrazoxane use in children with cancer: A pupulation-based study from Maritimes, Canada

Anthracycline induced cardiotoxicity is a well-recognized complication in pediatric oncology. The use of the cardio-protective drug dexrazoxane has gained traction despite its unclear efficacy and toxicity. A retrospective, population-based study was completed using chart and database information on children treated with anthracycline at the IWK Health Centre from 2009-2015 (n=178). The efficacy of dexrazoxane was defined as a lack of undesirable deviations in identified cardiac parameters on echocardiogram. Toxicity of dexrazoxane was defined as chemotherapy delays from any of decreased absolute neutrophil count (ANC), decreased platelets, increase in viral/bacterial episodes and febrile neutropenia (FN) episodes. Patients were stratified into groups based on the total amount of anthracycline received and whether they received dexrazoxane. Regardless of anthracycline dose, we found no significant relationships regarding cardiac function in the untreated and dexrazoxane treated groups. However, we found that patients who were treated with &gt;250mg/m2 of anthracycline and received dexrazoxane experienced significantly more platelet delays but no cardiac benefit (p=0.007). When classified by diagnosis, we also found that dexrazoxane treated patients diagnosed with low-risk acute lymphocytic leukemia (LR-ALL) were likely to experience a delay in treatment due to both low ANC (p=0.0001) and the development of FN (p=0.02) whereas high-risk acute lymphocytic leukemia (HR-ALL) patients were likely to experience treatment delays due to thrombocytopenia (p=0.03), low ANC (p=0.0001) and FN (p=0.0001). Despite finding no significant differences regarding the efficacy of dexrazoxane as a cardio-protectant, we have shown that its use induces non-cardiac toxicities in children with cancer that contribute to treatment delays.