Neutropenic Episodes Research Articles

Surveillance hématologique de la clozapine : les temps sont-ils venus d’assouplir les règles ?

BackgroundA significant proportion of people with resistant schizophrenia do not receive treatment with clozapine, despite its clearly established efficacy in this indication. The constraints associated with haematological monitoring are a major obstacle to clozapine use, resulting in a real loss of opportunity for the people concerned. ObjectiveThe aim of this opinion article is to question the relevance of maintaining the existing haematological monitoring rules for clozapine treatment. DiscussionRecent studies on the temporal evolution of agranulocytosis risk attributable to clozapine confirm that this risk becomes negligible after one to two years of treatment. Stringent haematological monitoring leads to unjustified discontinuation of clozapine, as transient neutropenic episodes, which may be linked to other causes are common in the general population. Haematological monitoring requires nursing time and sometimes complex organisational adaptations in outpatient facilities to ensure continuity of care, particularly at a time when medical and paramedical staffing levels are low. Haematological monitoring has already been reduced or suspended in several countries after the period of risk of agranulocytosis. ConclusionThe benefit/risk ratio of maintaining strict haematological monitoring rules for clozapine appears unfavourable, suggesting that the time may have come to reduce the risk of agranulocytosis.

Neoadjuvant Chemotherapy with Concurrent Letrozole for Estrogen Receptor-Positive and HER2-Negative Breast Cancer: An Open-Label, Single-Center, Nonrandomized Phase II Study (NeoCHAI).

The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon's minimax two-stage design; a pCR rate > 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33-63), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo-endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.

Time to antibiotic administration in patients undergoing HSCT with neutropenic fever.

e19501 Background: Cytotoxic chemotherapy for hematologic malignancies may adversely affect myelopoiesis, resulting in profound neutropenia that predisposes patients to severe infections. Patients undergoing hematopoietic stem cell transplantation (HSCT) are at particularly increased risk. Neutropenia is defined by an absolute neutrophil count (ANC) <500 cells/μL per complete blood count with differential. Neutropenic fever is a critical event with one-time temperature ≥101ºF or ≥100.4ºF sustained over one hour. Current standard-of-care is to initiate broad-spectrum antibacterial therapy within 30-60 minutes of presentation. MetroHealth Medical Center in Cleveland, Ohio launched a new Blood and Marrow Transplant program in 2023 in the state-of-the-art Glick Center. This retrospective study explores time to blood culture draw and initiation of antibiotics in HSCT patients with neutropenic fever. Methods: The MetroHealth HSCT database was used to identify hematologic malignancy patients status-post HSCT treated in the Blood and Marrow Transplant program. Tumor type and staging, chemo history, and infection prophylaxis (PPx) were recorded from chart review. Neutropenic fever episodes were identified by review of vitals history. Time to blood culture draw and antibiotic administration was then calculated from the medication administration record (MAR). Results: N = 11 hematologic malignancy patients status-post HSCT and chemotherapy were identified in the MetroHealth database. 8 presented with multiple myeloma (RISS stage II – IV), 2 with Hodgkin lymphoma, and 1 with mantle cell non-Hodgkin lymphoma. All patients were on Valtrex or acyclovir PPx, 10 on levofloxacin PPx, and 9 on fluconazole PPx. 6 of 11 patients had one documented episode of neutropenic fever each. ANC levels ranged from unidentifiable to 420 cells/μL. Half of the episodes saw blood culture draw within 1 hour and initiation of antibiotics in 60-90 minutes. The other 3 episodes saw culture draw at 2:13, 3:09, and 10:10 hours from fever and antibiotic administration at 12:00, 2:53, and 10:23 hours, respectively. Infectious disease (ID) specialists were consulted in each of the latter 3 cases. Conclusions: No patient at MetroHealth with neutropenic fever has seen appropriate initiation of antimicrobials within 30 to 60 minutes of presentation. Hypotheses for this delay include improper chart documentation, nurse training (delay in physician notification), and provider comfort (antimicrobials deferred to day team, ID consults). The latter is of particular concern given incidents of >10 hour delay to antibiotic initiation. Fortunately, there have not been any severe morbidity or mortality outcomes yet. Next steps are to deploy a quality improvement initiative to increase speed to fever identification, blood culture draw, and empiric antimicrobial delivery.

The prevalence of neutropenia and association with infections in patients with systemic lupus erythematosus: a Swedish single-center study conducted over 14 years

Hematologic abnormalities are common manifestations of SLE, although neutropenia is observed less frequently and is not included in the classification criteria. Nonetheless, neutropenia is a risk factor for infections, especially those caused by bacteria or fungi. We aimed to evaluate the impact of neutropenia in SLE through a systematic investigation of all infections in a large cohort of well-characterized patients, focusing on neutropenia, lymphopenia, and hypocomplementemia. Longitudinal clinical and laboratory parameters obtained at visits to the Rheumatology Unit, Linköping University Hospital, and linked data on all forms of healthcare utilization for all the subjects included in our regional SLE register during 2008–2022 were assessed. Data regarding confirmed infections were retrieved from the medical records. Overall, 333 patients were included and monitored during 3,088 visits to a rheumatologist during the study period. In total, 918 infections were identified, and 94 occasions of neutropenia (ANC < 1.5 × 109/L) were detected in 40 subjects (12%). Thirty neutropenic episodes in 15 patients occurred in association with infections, of which 13 (43%) required in-hospital care, 4 (13%) needed intensive care, and 1 (3%) resulted in death. Bayesian analysis showed that patients with ≥ 1 occasion of neutropenia were more likely to experience one or more infections (OR = 2.05; probability of association [POA] = 96%). Both invasiveness (OR = 7.08; POA = 98%) and severity (OR = 2.85; POA = 96%) of the infections were significantly associated with the present neutropenia. Infections are common among Swedish SLE patients, 12% of whom show neutropenia over time. Importantly, neutropenia is linked to both the invasiveness and severity of infections. Awareness of the risks of severe infections in neutropenic patients is crucial to tailor therapies to prevent severe illness and death.

Successful Management of Neutropenic Sepsis Is Key to Better Survival of Patients With Blood Cancer in Sri Lanka: Real-World Data From the Resource-Limited Setting.

Sepsis is the main cause of nonrelapse mortality, and there are no published data on applicability of supportive care protocols from high-income countries such as Sri Lanka. The aim of the study was to investigate management and mortality of neutropenic episodes among Hemato-Oncology patients. Retrospective analysis of clinical characteristics, management, morbidity, and mortality of neutropenic Hemato-Oncology patients presented to the Lanka Hospital Blood Cancer Centre from January 1, 2019 to December 31, 2019 was performed. A total of 169 neutropenic episodes were identified; 115 (68%) of such episodes were related to chemotherapy. Acute leukemia, lymphoproliferative disorders, and plasma cell disorders accounted for 23%, 69%, and 8% of patients, respectively. The median age of patients who had sepsis was 56 years, whereas that of those who had no sepsis was 53 years (P = .49). The median time to neutropenia was 9 days for those in the sepsis group compared with 8 days in the group that had no sepsis (0.64). The median neutrophil count in the group that had sepsis was 0.06, whereas it was 0.69 in the group that had no sepsis (P ≤ .05). The median time to commencement of antibiotics was 20 minutes. To our knowledge, this is the only documented study related to outcome and successful applicability of western supportive care protocols to Sri Lankan patients with neutropenia. In this study, we have shown that neutropenic sepsis can be successfully managed in the setting of limited resources with service development, following guidelines and staff training.

A Systematic Review of Three Biomarkers to Aid in the Assessment of Outcomes for Children and Young People with Cancer that are Febrile Neutropenic

For paediatric patients with cancer, febrile neutropenia (FN) is the most common complication of treatment. It requires inpatient hospitalisation and treatment with empirical broad-spectrum antibiotics. Approximately 20-30% of febrile neutropenic patients have a documented infection, thus needing antibiotics. For the rest, it is suggested that the cause of FN could be a viral or fungal infection, the malignancy itself, drug related or the result of a blood transfusion reaction as examples, therefore not requiring antibiotics. With no risk-stratification tool in use in practice to distinguish between patients who are at high or low risk of bacterial infections, recent studies have focused on identifying clinical and laboratory markers for this. This systematic review will focus on three biomarkers, C-reactive protein (CRP), presepsin (sCD14-ST) and lactate, to find their sensitivities and specificities for diagnosing bacterial infections and thus help determine the risk of poor outcomes for patients with FN. This review has systematically searched for relevant primary research papers. These studies have been critically appraised using a validated critical appraisal tool. Data from these studies were then extracted using a data extraction form, and evidence summarised. The findings have been interpreted, and the implications to practice and research are discussed. 1051 febrile neutropenic episodes from 743 children from different countries were analysed. In the majority of studies (75%), acute lymphoblastic leukaemia was the most frequent diagnosis. Eight of the studies in this review are looking at CRP. Two studies are looking at lactate, and five review presepsin. Lactate is a sensitive and specific biomarker with a lactate level ≥ 2mmol/L and &gt;2.5mmol/L showed sensitivities of 81% and 80% and specificities of 83% and 92.1%, respectively. Presepsin and CRP had mixed results for its sensitivity and specificity. Lactate and CRP are useful biomarkers for assessing the outcomes of children with FN and could be added to a CDR. This review cannot confirm that presepsin is a useful biomarker for practice and, therefore, cannot justify adding it to a CDR.

Invasive Fungal Infections in Children with Acute Leukemia: Epidemiology, Risk Factors, and Outcome.

Invasive fungal infections (IFI) cause morbidity and mortality in children with acute leukemia (AL). We retrospectively collected data on febrile neutropenic episodes (FNE) in AL children (2016-2021) and assessed factors associated with proven/probable IFI. Ninety-three children developed 339 FNE. Seventeen (18.3%) children developed 19 proven/probable IFI (11 yeast; eight molds). The proven/probable yeast IFI rate was 6/52 (11.5%) in children who belong to the high risk for IFI category (HR-IFI-AL: high-risk acute lymphocytic leukemia (ALL), acute myeloid leukemia, relapse); and 5/41 (12.2%) in the non-HR-IFI-AL category (standard/intermediate risk ALL). The proven/probable mold IFI rate was 7/52 (13.5%) in HR-IFI-AL children and 1/41 (2.4%) in the non-HR-IFI-AL category. In the multivariable analysis, underlying genetic syndrome, oral mucositis, and older age were significantly associated with proven/probable IFI, while a longer time since AL diagnosis was protective. Two of 13 (15.4%) HR-IFI-AL children died because of IFI. The elevated risks of proven/probable mold IFI and the associated mortality in HR-IFI-AL children, and high risk of invasive candidiasis in the non-HR-IFI-AL group, emphasize the need for the close monitoring of local epidemiology and the adjustment of practices accordingly.

Markers of intestinal mucositis to predict blood stream infections at the onset of fever during treatment for childhood acute leukemia.

Despite chemotherapy-induced intestinal mucositis being a main risk factor for blood stream infections (BSIs), no studies have investigated mucositis severity to predict BSI at fever onset during acute leukemia treatment. This study prospectively evaluated intestinal mucositis severity in 85 children with acute leukemia, representing 242 febrile episodes (122 with concurrent neutropenia) by measuring plasma levels of citrulline (reflecting enterocyte loss), regenerating islet-derived-protein 3α (REG3α, an intestinal antimicrobial peptide) and CCL20 (a mucosal immune regulatory chemokine) along with the general neutrophil chemo-attractants CXCL1 and CXCL8 at fever onset. BSI was documented in 14% of all febrile episodes and in 20% of the neutropenic febrile episodes. In age-, sex-, diagnosis- and neutrophil count-adjusted analyses, decreasing citrulline levels and increasing REG3α and CCL20 levels were independently associated with increased odds of BSI (OR = 1.6, 1.5 and 1.7 per halving/doubling, all p < 0.05). Additionally, higher CXCL1 and CXCL8 levels increased the odds of BSI (OR = 1.8 and 1.7 per doubling, all p < 0.0001). All three chemokines showed improved diagnostic accuracy compared to C-reactive protein and procalcitonin. These findings underline the importance of disrupted intestinal integrity as a main risk factor for BSI and suggest that objective markers for monitoring mucositis severity may help predicting BSI at fever onset.

A Retrospective Study of the Association between Respiratory Tract Viral PCR Panel Results and Clinical Outcomes in Children with Cancer and Febrile Neutropenia and Review of the Literature

Abstract Objective The role of respiratory viral pathogens (RVPs) in children with cancer having febrile neutropenic (FEN) episodes has not been well studied. The objectives of this study were to investigate the prevalence and clinical outcomes of RVP in this group. Methods Pediatric patients with cancer and an episode of FEN, presenting between March 2021 and March 2022 were included. All data were retrospectively retrieved from patient files. A throat swab sample was obtained for the detection of 17 RVPs and evaluated by a polymerase chain reaction (PCR) method. Results A total of 110 (male n = 76; 69.1%) patients with a mean ± standard deviation age of 6.68 ± 4.92 years were included. Reproduction in PCR was seen in 76 (69.1%) children. Rhinovirus (31.6%) and respiratory syncytial virus (15.8%) were the most frequently detected viruses. Mixed respiratory viruses (coinfections of ≥2 viruses) were only seen in 13%. The median (range) duration of hospitalization was 11 (2–143) days, and 8.2% of the children were admitted to the pediatric intensive care unit (PICU). The median (range) length of stay (LOS) in the PICU was 8 (1–100) days. Overall mortality rate was 3.6%. There was no significant difference in LOS in the hospital, rate of admission to PICU, LOS in the PICU, and the mortality rate between children with and without growth in PCR (p &gt; 0.05). Conclusion There was high prevalence of RVP in children with cancer and FEN. However, given that having a positive RVP does not affect LOS in the hospital/PICU or disease severity, in this population, there was no association between positive PCR findings and clinical features investigated or outcome.

Classification of Chemotherapy-Induced Febrile Neutropenic Episodes Into One of the Three Febrile Neutropenic Syndromes.

Introduction Febrile neutropenia is a commonly encountered medical emergency in patients undergoing cancer treatment and can delay and modify the course of treatment and even lead to dire outcomes, including death. The cause of fever in a post-chemotherapy-induced neutropenic patient can be confusing to treating physicians. A review of the literature demonstrated that blood culture results could determine the cause of febrile neutropenia in only approximately 10% to 25% of patients. The objective of our study was to measure the incidence of positive blood cultures, urine cultures, and other body fluid cultures resulting in chemotherapy-induced neutropenia and further classify fever episodes into three neutropenic fever syndromes, such as microbiologically documented, clinically suspected, or unknown causes of fever, respectively. Methods We conducted a prospective observational study on 399 chemotherapy-induced neutropenic fever episodes with the aim of classifying them into one of the three neutropenic syndromes. Wetried to document the cause of the fever in these patients. We also noted the type of cancer treatment regimen they were on and correlated their clinical profile with their body fluid cultures, including blood cultures, urine cultures, and other body fluid cultures. We then categorized each fever episode into one of three neutropenic syndromes. Results We studied 399 febrile neutropenic episodes. We were able to microbiologically document the cause of fever in 39% of the cases, and we obtained growth in 51 out of 399 blood cultures (13%), which was comparable to the available literature, and urine culture showed growth in 62 out of 399 cultures (16%), while other body cultures such as pus culture, bile culture, and bronchioalveolar lavage cultures collectively showed growth in 42 out of 399 episodes (10%). The most common bacteria isolated in both blood and urine cultures were Escherichia coli. Cumulatively, including blood, urine, and body fluid cultures, we were able to classify 39% (155 out of 399 cases) of febrile neutropenic episodes as microbiologically documented. The cause of fever was clinically suspected by means of careful history taking and an extensive physical examination in 31% (125 out of 399) without growth evidence in blood cultures, urine cultures, or any other body fluid culture. The cause of fever remained unknown in 119 cases (30%) of patients and was classified under the unknown cause of fever. Conclusions We conclude by stating that the study of fever in a neutropenic patient should include a thorough history and clinical evaluation of blood, urine, and other body fluid cultures instead of solely relying on blood culture results. We recommend further classifying patients into one of the three neutropenic fever syndromes, such as those that are microbiologically documented, clinically suspected, or unknown. Our blood cultures were able to give us a 13% positivity rate, whereas microbiologically, we were able to isolate an organism likely causing feverin 39% of patients. The cause of fever was suspected clinically in 31% of patients, but we were unsuccessful in microbiologically documenting any culture growth in blood, urine, or any other body fluid culture. The cause of fever remained a mystery and unknown to us without any microbiological or clinical cues in 119 cases (30%) of febrile neutropenic episodes.

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.

Validation of National Early Warning Score and Quick Sequential (sepsis-related) Organ Failure Assessment in acute myeloid leukaemia patients treated with intensive chemotherapy.

Chemotherapy-induced neutropenia in acute myeloid leukaemia (AML) is a risk factor for life-threatening infections. Early diagnosis and prompt interventions are associated with better outcomes, but the prediction of infection severity remains an open question. Recently, National Early Warning Score (NEWS) and quick sequential organ failure assessment (qSOFA) scores were proposed as warning clinical instruments predicting in-hospital mortality, but their role in the haematological context is still unknown. We retrospectively assess the predictive role of NEWS and qSOFA in a large and homogeneous cohort of adult AML patients treated with intensive chemotherapy. In a total of 1048 neutropenic episodes recorded in 334 consecutive patients, the scores were applied to predict outcomes on the same day of fever onset, and after 24 and 48 h from score calculation. Both NEWS and qSOFA significantly predicted death, with more accuracy on the same day (NEWS AUROC 0.984 and qSOFA AUROC 0.969) and after 24 h (NEWS AUROC 0.928 and qSOFA AUROC 0.887), while remained moderately accurate after 48 h. Furthermore, also ICU admission was accurately predicted at fever onset and after 24 h. Both scores were useful tools in the management of post chemotherapy neutropenic febrile AML patients.

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.

Chemotherapy-Induced Oxidative Stress in Pediatric Acute Lymphoblastic Leukemia.

Introduction Plasma antioxidant capacity in children receiving chemotherapy decreases due to the effect of the disease and chemotherapy. Increased oxidative stress (OS) predisposes to an increased risk for chemotherapy-related toxicity and febrile neutropenic episodes. Materials and methods We conducted this case-control study in the hematology-oncology unit of the department of pediatrics of a tertiary hospital in Delhi, India, from November 2017 to March2019to compare OS between children with acute lymphoblastic leukemia (ALL) and healthy controls. We estimated the trends in OS as measured by the plasma total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) levels at baseline and at the completion of induction I (four weeks), induction II (eight weeks), and induction IIA-consolidation (16 weeks) phases of chemotherapy in children with ALL. We also assessed the change in OS during different phases of initial treatment and studied the association between OS and the hematological toxicity of chemotherapy (determined by the need for blood component therapy and the number of febrile neutropenic episodes) and serum cobalamin and folate levels. Results OS was significantly higher in children with ALL at diagnosis (n=23) compared to controls (n=19).The median (interquartile range (IQR)) TAC levels (mM) were significantly lower (1.21 (1.05-1.26) versus 1.28 (1.26-1.32), P=0.006), and TBARS levels (nmol/mL) were significantly higher (312.0 (216.6-398.0) versus 58.5 (46.2-67.2), P<0.001) in children with ALL at diagnosis compared to controls. OS was highest at the end of the induction I phase (four weeks) despite the patients being in clinical and hematological remission. OS at the completion of intensive chemotherapy (16 weeks) was higher than at diagnosis. A significant correlation was found between serum folate levels and TAC levels at baseline (P=0.03). Serum cobalamin levels, the need for blood component therapy, and the number of febrile neutropenic episodes did not have any association with OS. Conclusion Children withALL had significantly higher OS compared to controls, indicating that underlying disease affects the oxidative balance unfavorably. Chemotherapy itself increases oxidative stress.

Investigation of Candidemia Diagnosis by PCR Method in Febrile Neutropenic Patients with Hematological Malignancies

Objective: Candidiasis" is the predominant fungal infection that occurs invasively and opportunistically in individuals with compromised immune systems. Febrile neutropenia patients receiving cytotoxic chemotherapy due to malignancy, especially acute leukemia and stem cell transplantation are at greater risk among many others. In this study, it was aimed to search for Candida DNA to make an early diagnosis by using PCR method Materials &amp; Method: This prospective study was conducted in Pediatric Hematology Transplantation Clinic of Akdeniz University. The study enrolled 78 patients with malignancies and candidiasis infection who were experiencing febrile neutropenia. The febrile neutropenic episodes were identified prospectively by monitoring the daily leukocyte counts and fever symptoms of the patients. Results: Candida was grown in the blood cultures of seven (9%) of the febrile neutropenic patients included in the study. All of the breeding Candidas were C.albicans. The underlying primary diagnosis of 6 (85.7%) of the febrile neutropenic patients with reproduction was hematological malignancy, while the underlying primary diagnosis of one (12.5%) was solid malignancy (Neuroblastoma). PCR detected Candida DNA in 9% of Febrile Neutropenic patients. C.albicans was grown in the blood cultures of all patients with Candida DNA. Conclusion: As a result, The conclusion drawn was that in cases where candidemia is suspected, particularly in febrile neutropenic patients with hematological malignancies who are immuno-compromised and at high risk of mortality, rapid and accurate diagnosis using Candida PCR with high sensitivity and specificity is necessary.

One Hundred Consecutive Neutropenic Febrile Episodes Demonstrate That CXCR3 Ligands Have Predictive Value in Discriminating the Severity of Infection in Children with Cancer.

This study assesses the value of the CXCR3 ligands CXCL9/MIG, CXCL10/IP-10 and CXCL11/I-TAC when used to supplement the standard infection markers C-reactive protein (CRP) and procalcitonin (PCT) in the diagnostic algorithm of neutropenic fever in children with cancer. The concentration of CRP, PCT and chemokines was determined during the first hour of fever and 12-24 h afterwards in pediatric oncology patients with neutropenia. Among 100 consecutive febrile episodes in neutropenic patients, 34 cases demonstrated fever of unknown origin (FUO) (group A), 47 demonstrated mild clinically or microbiologically proven infection (Group B) and 19 severe infection (Group C). Significantly higher PCT-1 levels were found in group C (0.24 ng/mL) vs. group A (0.16 ng/mL), and PCT-2 in group C (1.2 ng/mL) vs. A (0.17 ng/mL), and in C vs. B (0.2 ng/mL). Chemokine concentrations (I-TAC-1, IP-10-1, IP-10-2) were significantly lower in Group A vs. B+C; I-TAC 1: 48.64 vs. 70.99 pg/mL, p = 0.03; IP-10 1: 59.95 vs. 96.84 pg/mL, p = 0.04; and IP-10 2: 102.40 vs. 149.39 pg/mL, p = 0.05. The selected pro-inflammatory chemokines I-TAC and IP10 might help to distinguish cancer patients with febrile neutropenia with the highest risk of infection. Although procalcitonin could serve as a marker of a high risk of infection, its delayed response diminishes its usefulness.

1773. Evaluation of Fluoroquinolone Prophylaxis in Preventing Bacterial Infection in Neutropenic Afebrile Patients Without Leukemias or HSCT: A Systematic Review

Abstract Background Per 2010 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer, routine use of fluoroquinolone (FQ) chemoprophylaxis in low-risk populations (defined as those with solid tumors or lymphoma undergoing chemotherapy) is not recommended to prevent febrile neutropenic episodes as it was not found to impact all-cause mortality. Since these guidelines were published, there have been additional randomized trials (RCTs) of FQ chemoprophylaxis in patients with cancer. Our objective was to assess the efficacy of FQ vs placebo in preventing probable or confirmed bacterial infection in patients with cancer who did not have leukemias or hematopoietic stem cell transplant (HSCT). Secondary outcomes of interest included febrile episodes, mortality, and adverse effects of antibiotic use. Methods Medline via PubMed, The Cochrane Central Register of Controlled Trials, and SCOPUS from inception through 2/17/2022 were searched. We included RCTs in English comparing FQ to placebo in preventing neutropenic fever and bacterial infections in patients with cancer who did not have leukemias or HSCT. Results We included 5 RCTs (N= 3158). The rates of probable or confirmed bacterial infection in patients with cancer revealed 541/1562 (34.6%) infections in the FQ group and 679/1560 (43.5%) in the placebo group (OR: 0.68, 95% CI:0.59,0.79, I2 = 57%, p=0.002). In evaluating development of febrile episodes, 300/1566 (19.2%) events were noted in the FQ group and 407/1555 (26.2%) in the placebo group (OR: 0.58, 95% CI:0.41,0.83, I2 = 0%, p&amp;lt; 0.001). Mortality events in the FQ group were 113/1597(7.1%) and 124/1508 (8.2%) in the placebo group (OR: 0.76, 95% CI:0.53,1.1, I2 = 7%, p=0.15). Adverse events associated with antibiotic use in the studies were more frequent in the FQ group. Figure 1Forest Plot of Mortality in included studiesFigure 2Results on Development of Fevers in included studies.Figure 3Forest plot of Probable or Proven Infection in included studies. Conclusion Although evidence does not show that FQ prophylaxis provides mortality benefit, it did show a decrease in development of bacterial infections and febrile episodes. This suggests that treatment may still provide clinical benefit to this population of patients, but must be weighed against risks and consequences of long-term antibiotic use, which were not reported by the included studies. Disclosures All Authors: No reported disclosures.

Infectious Complication During Induction Chemotherapy in Children with Acute Myeloid Leukemia- A Single Center Study

Background: Acute Myeloid Leukemia (AML) contributes to about 20% of leukemia. Most of the AML patients suffer from infection.&#x0D; Objective: To evaluate the rate of infection, type and site of infection, organisms responsible for infection and to assess antibiotic sensitivity pattern and infection related mortality in AML.&#x0D; Material &amp; Methods: Newly diagnosed AML patients aged between 1-18 years, admitted to receive induction chemotherapy were enrolled. They received induction of chemotherapy according to Modified MRC’ 12 in our department. Patient was on followup throughout the induction period and all the infectious complication occurred during this period were analyzed.&#x0D; Result: A total of 38 episodes of infection developed in 34 patients in both cycles of induction (1.12 episodes/ patient). Among the total 38 episodes of infection, fever was the commonest clinical presentation. In both chemotherapy cycles, 7(18.4%) episodes of infection were culture positive. A total of 9 organisms were isolated of which most of them was gram-negative. Fever without focus was found in 15(39.5%) episodes. Profound neutropenia was present in 15(39.47%) episodes and profound neutropenic episodes were found to be culture positive in 5(71.4%) cases. About 6(17.5%) patients died during 1st cycle of induction.&#x0D; Conclusion: Among children with AML, profound neutropenic cases had high susceptibility to culture positive infection. Further prospective study is needed to identify means to prevent infectious complication of AML patients receiving induction chemotherapy particularly in those with profound neutropenia.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (3) : 134-140

Administration of Obinutuzumab, and Not Rituximab, during Induction and Maintenance for Follicular Lymphoma Increases the Likelihood of Developing Delayed Neutropenia

The results of the PRIMA trial published a decade ago, substantiated the benefit of maintenance therapy with anti-CD20 monoclonal antibodies (MoAb), following chemo-immunotherapeutic induction, for prolongation of the progression-free survival (PFS) of patients with high-tumor- burden follicular lymphoma (FL). Rituximab-associated delayed neutropenia, defined as an event occurring after recovery of cytopenias related to the chemotherapy backbone, has been reported in lymphoma patients, with the prevalence varying between 8-27%. Several mechanisms have been implicated in its pathogenesis, mainly related to B-cell recovery, such as a disrupted stromal-derived factor-1 gradient and the generation of anti-neutrophil antibodies. The available data associated with anti-CD20 MoAb-mediated delayed neutropenia during the prolonged (2-year) maintenance treatment in FL are limited, and the consequences of its occurrence remain unclear. The aims of this study were to assess the prevalence of neutropenia and risk factors for its development in FL patients during maintenance therapy as well as to evaluate its severity and impact on decisions regarding modification of the original treatment protocol. In this retrospective study, clinical data were retrieved from electronic medical records of FL patients treated at the Rambam Health Care Campus between 2006 (when maintenance therapy was first applied) and 2021. Continuous variables were statistically processed using the Mann Whitney U test and categorical variables - using Fisher exact tests. Statistical significance was defined as p <0.05. During the study period, a total of 305 patients treated for high-tumor-burden FL were identified in the institutional database; 164 of these patients (53.8%) also received maintenance therapy with anti-CD20 MoAb (rituximab or obinutuzumab). Data on 157/164 patients were included in the final analysis after the exclusion of 7 patients due to their concomitant autoimmune disease. During maintenance therapy, 37/157 (23.6%) patients developed delayed neutropenia, with 4/37 (11%) of them experiencing at least one recurrent event. This relatively high percentage of delayed events is comparable only to that observed in a study which evaluated heavily pretreated lymphoma patients (Cattaneo C et al. Leuk Lymphoma, 2006), exposed to highly myelotoxic regimens or fludarabine and did not include a maintenance phase. Median time from the start of maintenance to the first neutropenic episode in the current study was 5 (range 1.5-12) months and the majority of these events were of high grade (III and IV in 24% and 38% of patients, respectively). Despite the fact that 15/37 (40%) patients who developed this complication were hospitalized with neutropenic fever, the occurrence of neutropenia led to early discontinuation of maintenance treatment solely in 14% of the cohort and had no effect on PFS, measured at a median follow-up of 91.5 months. Univariate and multivariate analyses identified the use of the obinutuzumab/bendamustine (O/B) combination for induction therapy, or maintenance with obinutuzumab (O) as the only risk factors of delayed neutropenia development in patients on maintenance therapy (odds ratios in case of O/B induction followed by O maintenance: 4.433 [95%CI=1.387-14.17, p=0.012]; in case of O maintenance: 3.048 [95%CI=1.207-7.697, p=0.018]). All other laboratory and clinical factors examined did not impact late neutropenia occurrence (Table 1). The current study demonstrates that the administration of obinutuzumab both as part of induction with bendamustine and as maintenance therapy increases the likelihood of developing anti-CD20 MoAb-induced delayed neutropenia, suggesting that pharmacokinetic differences between type I and type II MoAb are partly responsible for this effect. Moreover, the findings regarding the prevalence of neutropenia and time to its first episode in this study cohort do not support the involvement of processes related to B-cell recovery in the pathogenesis of this complication during maintenance treatment, and warrant investigation of alternative mechanisms. The risk factors for delayed neutropenia in FL patients on maintenance therapy, identified in this study, should be considered in the treatment paradigm for older frail patients who are more prone to complications of neutropenic fever. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pegfilgrastim Versus Filgrastim in the Supportive Care of Heavily Pretreated Multiple Myeloma in Treatment with Pomalidomide-Dexamethasone

The objective of this study was to compare the efficacy and safety of pegfilgrastim in patients affected by heavily pretreated MM, treated with pomalidomide-dexamethasone, in order to determine whether a single subcutaneous injection of pegfilgrastim is as effective as daily injections of standard filgrastim, in terms of haematological toxicity, febrile neutropenic episodes, antibiotic usage and hospedalization duration. 57 patients (31 M and 26 F) were enrolled, median age at diagnosis 69 years (r. 52-84), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-12), every refractory to all the drugs previously received, received Pomalidomide-Dexamethasone (P 4 mg for 21 days, D 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. Since first course, received in domestic setting, with a very good compliance, patients performed blood counts once weekly and received, from day +8 to day +19, prophylactic oral chinolonic antibiotics and anti-fungal drugs. During neutropenia after first cycle, Filgrastim (5 μgr/kg/day for 3 days) was given if neutrophils count was <1500 x 10^9 cells/L. Median number of filgrastim administrations was 4.6 (r. 3-6); nadir neutropenia was registered after a median of 10.4 days (r. 7-14); median of nadir neutrophil count was 1.13 x 10^9 cells/L (r.0.3 - 1.5), with maximum duration of 14 days. From the second course, all patients switched to prophylaxis with pegfilgrastim (6 mg), injected subcutaneously with a single administration on day +3 independently from the neutrophil count at that time. During pegfilgrastim, neutropenia was never longer than 8 days, with a consequent reduction of neutropenia-related infections. Median nadir neutrophil count, evaluated for every patients for at least three courses of therapy (r. 3-6) registered at day +11, was 1.28 (r.0.9-2.2). Only 4 patients needed a supplement of 3 administrations of filgrastim. Pegfilgrastim was well tolerated in all patients: main side effects in our patients were mild fever and bone pain (21.2%). In patients affected by heavily pretreated MM treated with pomalidomide-dexamethasone, pegfilgrastim seems to reduce the incidence of severe neutropenia and infections and may increase the possibility to maintain the scheduled time of treatment.