Absolute Neutrophil Count Research Articles

Clinical and Laboratory Characteristics of Pediatric Patients With ACKR1/DARC-Associated Neutropenia.

ACKR1/DARC-associated neutropenia (ADAN), resulting from homozygosity for a single nucleotide polymorphism (SNP) in the ACKR1/DARC gene (rs2814778), is a common cause of benign neutropenia that primarily affects individuals of African and Jewish Yemenite descent. We aimed to characterize ADAN in pediatric patients in Israel, given its ethnically diverse population. We assessed children with isolated neutropenia treated during 2018-2023 at one pediatric center, for the ACKR1/DARC polymorphism, using Sanger sequencing or targeted next-generation sequencing. Of 115 patients evaluated, 49 (42.6%) were diagnosed with ADAN; of these, 29 (59%) had absolute neutrophil counts in the severe range (0-0.5×109/L) at diagnosis. The allele distribution revealed 37% of Muslim Arab and 61% of Jewish origin. Yemenite, Ethiopian, Mediterranean, Asian, and European ancestry were included; 59% had a family history of neutropenia. The median age at the first neutropenia detection was 1.2years; 91.8% were identified during routine blood counts. The median absolute neutrophil count at diagnosis was 0.5×109/L (interquartile range: 0.3). An increased susceptibility to infections was not found either before or during the median follow-up period of 2.5years (interquartile range: 1.54) after the diagnosis of ADAN. In 34 patients (72.3%), neutrophil counts were in the normal range during febrile illnesses. We identified ADAN in individuals of variable ethnicities, almost half with severe neutropenia. We recommend testing for ADAN in all children with isolated neutropenia without severe infections. Homozygosity for the ACKR1/DARC rs2814778 SNP may obviate the need for further investigation, follow-up, or treatment in specific clinical scenarios.

Emapalumab Treatment in Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis in the United States: A Retrospective Medical Chart Review Study.

Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH. REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH. Fifteen of 105 patients (14.3%) had rheumatologic disease-associated HLH. Of these, nine (60.0%) had systemic juvenile idiopathic arthritis, and one (6.7%) had adult-onset Still disease. Median (range) age at HLH diagnosis was 5 (0.9-39) years. Most patients (9 of 15; 60.0%) initiated emapalumab in an intensive care unit. Emapalumab was most frequently initiated for treating refractory or recurrent (10 of 15; 66.7%) disease. Most patients received HLH-related therapies before (10 of 15; 66.7%) and concurrently with (15 of 15; 100.0%) emapalumab. Emapalumab-containing regimens stabilized or achieved physician-determined normalization of most laboratory parameters, including absolute neutrophil count and absolute lymphocyte count (13 of 14; 92.9%), chemokine ligand 9 (9 of 11; 81.8%), and platelets and alanine transaminase (11 of 14; 78.6%), and reduced glucocorticoid dose by 80%. Overall survival and 12-month survival probability from emapalumab initiation were 86.7%. Emapalumab-containing regimens stabilized or normalized most key laboratory parameters, reduced glucocorticoid dose, and were associated with low disease-related mortality, thereby demonstrating potential benefits in patients with rheumatologic disease-associated HLH.

The Impact of Inflammatory Markers and Obesity in Chronic Venous Disease

Background: Chronic venous disease (CVD) represents a significant health challenge, particularly in obese individuals. This study focuses on the interplay between inflammation, obesity, and CVD, by analyzing the role of inflammatory markers in the disease progression. Methods: Clinical and paraclinical data of 619 patients hospitalized and treated in the Phlebology Department (1stSurgical Department, “Pius Brînzeu” Emergency County Hospital Timișoara, Romania) between 2018 and 2024 were analyzed. Results: The statistical analysis revealed that age, C-reactive protein (CRP), fibrinogen, and absolute neutrophil count (ANC) were key predictors of CVD progression. Specifically, elevated CRP and fibrinogen levels correlated strongly with increased CVD severity, particularly in patients with higher body-mass index (BMI). BMI, while not an independent predictor, contributed indirectly to the disease severity through its association with these inflammatory markers. The logistic regression model incorporating age, BMI, CRP, fibrinogen, and ANC demonstrated a high predictive accuracy, with an area under the curve (AUC) of 0.902, highlighting the models reliability in stratifying patients at risk for severe CVD. Conclusions: This predictive model not only aids in identifying high-risk patients but also reinforces inflammation as a critical therapeutic target in CVD management.

Clearing the Air: Acute Invasive Fungal Rhinosinusitis in Hematologic Cancer Patients.

Air quality has been shown to impact the rates of fungal infection of the airway, causing diseases such as acute invasive fungal rhinosinusitis (AIFRS), particularly in immunocompromised patients. We theorize that patients with hematologic malignancies in units with aging air handling units (AHUs) have a higher attack rate of AIFRS. Retrospective chart review identified patients with hematologic malignancy and AIFRS in two distinct and equal time periods between 2013 and 2022, representing the presence of aging AHUs and new AHUs, respectively. Cubic feet per minute (CFM) air flows, AIFRS attack rates, and clinical data were compared between the two groups and statistical analyses performed. The older AHUs produce air flow of 27,610 CFM and the newer AHUs produce air flow of 80,000 CFM. There were 18 patients with air supplied by older AHUs and 7 patients with air supplied by new AHUs who developed AIFRS. There was a significantly higher AIFRS attack rate for patients supplied by the older AHUs compared with patients supplied by newer AHUs (p = 0.033). The patients supplied by the older AHUs tended to be younger. The white blood cell counts, absolute neutrophil counts, and the mean time to diagnosis did not differ between the two groups. To our knowledge, this is the first study to examine AIFRS in immunocompromised patients' inpatient environment. Further research should explore whether higher CFM AHUs can decrease this disease among our most vulnerable patients. 3 Laryngoscope, 134:4466-4470, 2024.

Alternative therapy for lymphoma with febrile neutropenia using traditional Chinese medicine: A case report

IntroductionFebrile neutropenia is a common complication in patients undergoing chemotherapy for hematologic malignancies and is associated with significant morbidity and mortality. Primary granulocyte colony-stimulating factor (G-CSF) prophylaxis is consistently associated with a notable reduction in the risk of febrile neutropenia. However, the use of G-CSF in patients who are already neutropenic from chemotherapy remains controversial. Studies have shown that 12.9% of cancer patients incorporate traditional Chinese medicine (TCM) to alleviate chemotherapy side effects in Taiwan; thereby providing an alternative management strategy for neutropenic fever in cancer patients. Case presentationThis is an 18-year-old female with newly diagnosed precursor T-lymphoblastic lymphoma. After chemotherapy, the patient developed febrile neutropenia. Despite the use of antibiotics and G-CSF, the febrile neutropenia persisted for two months. Approximately ten days after the initiation of traditional Chinese medicine decoction with the strategy of tonifying the spleen and stomach, clearing yin fire, and uplifting yang, her absolute neutrophil count (ANC) had gradually increased. Additionally, after two weeks of treatment, her fever subsided. The patient continued with chemotherapy and was discharged in stable condition. DiscussionAntibiotic use aligns with the TCM perspective of an “attack” approach. Conversely, our TCM decoction was designed to raise the ANC by tonifying the spleen and stomach, clearing Yin Fire, and uplifting Yang. Li Dongyuan, one of the four great masters of the Jin Yuan Dynasty, created the formula: Bupiwei Shengyang Sanhuo Decoction that is notable in this regard. The herbs in our decoction have shown hematopoietic and myelosuppression-alleviating effect. For many patients who do not respond adequately to G-CSF alone, integrative treatments involving both TCM and Western medicine can offer additional therapeutic benefits by increasing blood cell counts.

Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing.

Oral mucositis affects about 20% of children undergoing high-dose methotrexate (HDMTX) for acute lymphoblastic leukemia (ALL), despite existing management strategies. Personalized HDMTX dosing, adjusted by pharmacokinetics and leukemia risk, has reduced mucositis incidence, but variations still occur with similar 24-h methotrexate levels. This retrospective study investigated risk factors for oral mucositis under individualized methotrexate protocols. Data from patients with ≥ Grade 2 oral mucositis (CTCAE v4.0) were analyzed from the St. Jude Children's Research Hospital total 16 trial. A 1:1 case-control matching method considered age, sex, risk classification, immunophenotype, and methotrexate course. McNemar's, Bowker's symmetry, and Wilcoxon signed-rank tests were used for statistical analyses. Risk factors for recurrent mucositis were identified in a case-only analysis. The study found significant associations between methotrexate-induced mucositis and new-onset skin rashes (p = 0.0027), fever (p = 0.0016), neutropenic fever (p = 0.0008), lower absolute neutrophil count (p < 0.0001), acute kidney injury (AKI) (p = 0.0164), delayed methotrexate clearance (p = 0.0133), and higher 42-h methotrexate levels (p = 0.0179). In the standard/high-risk group, mercaptopurine dose was also linked to mucositis (p = 0.0495). Multivariable analysis showed that skin rashes (OR 6.5, p = 0.0016), fever (OR 2.8, p = 0.009), and neutropenia (OR 2.3, p = 0.0106) were independent risk factors for mucositis. Female sex (OR 7.12, p = 0.015) and AKI (OR 3.819, p = 0.037) were associated with recurrent mucositis. Fever, skin rashes, AKI, delayed methotrexate clearance, and higher 42-h methotrexate levels were key risk factors for HDMTX-induced oral mucositis. Skin rashes, fever, and neutropenia were independent predictors, while female sex and AKI were linked to recurrent mucositis.

Human body resistance dynamics in the post-covid period

The issue of the state of specific and nonspecific resistance in the post-COVID period and the possible consequences of COVID-19 remains poorly understood. A clinical and laboratory examination of 124 patients was conducted at various time points after COVID-19 infection. 62 patients recovered completely and 62 had post-COVID syndrome. The leukocyte count and leukogram were evaluated in all patients. Immunogram parameters were additionally evaluated in patients with post-COVID syndrome. The results showed that, regardless of post-COVID syndrome, leukocyte count is lower in all patients within six months after COVID-19 infection than in unaffected subjects. The absolute neutrophil count is restored only 12 months later. In the presence of post-COVID syndrome, the absolute number of CD3+, CD4+and CD19+lymphocytes was lower than in healthy people. At the same time, 3 to 15 months after that, IgA titer in patients with PCS was significantly lower and that of for total IgM and IgG was higher without any clinical or laboratory signs of inflammation. The total blood IgE level was significantly higher and increased by the end of the observation period. A decreased activity of nonspecific protection, as well as indicators of cellular and humoral immunity in patients with post-COVID syndrome is accompanied by higher rate of viral and bacterial infections of various localization. Whereas during the first period an increase in total blood ID is not accompanied by clinical signs of atopy, then 6 months later the frequency of allergy increases. During the same period, cases of a joint syndrome revealed as arthralgia or progressive joint destruction become more frequent. Atopic manifestations are often combined with joint syndrome. Thus, after a COVID-19 infection, a low long-term level of nonspecific protection remains in vivo. In patients with post-COVID syndrome, low nonspecific and specific body resistance is manifested by viral and bacterial infections of the mucous membranes and skin. An imbalance in the immune system contributes to developing allergic and autoimmune processes.

Decreased neutrophils are associated with reduced risk of Type 2 Diabetes Incidence: Results from the CORDIOPREV study.

Numerous studies have reported an association between neutrophils and T2DM, although this relationship remains unclear. This study aims to investigate the interaction of neutrophils and a dietary intervention on T2DM incidence after 60 months of follow-up. A comprehensive analysis was conducted on the framework of the CORDIOPREV study, which included 462 patients without T2DM at the beginning of the study. They were randomly assigned to either a Mediterranean or a low-fat diet, of whom 107 developed T2DM. Absolute neutrophil counts and other related-ratio, were measured. Kaplan-Meier curves showed that the lowest tertile of basal neutrophils was associated with a reduced likelihood of T2DM incidence when compared to the middle [HR=0.499 (95%CI, 0.287-0.866)] and the highest tertiles [HR=0.442 (95%CI, 0.255-0.768)] in overall population, after adjusting for clinical variables. This association only remained significant in patients who follow a Mediterranean diet when compared the lowest to the middle [HR=0.423 (95% CI, 0.213-0.842)] and the highest tertiles [HR=0.371 (95% CI, 0.182-0.762)]. The predictive capacity yielded an AUC of 0.711 (95%CI: 0.652-0.769), being neutrophils the most important variable in the in the model. Decrease in neutrophils over the 60 months were associated with increased insulin sensitivity index (ISI) (R=-0.31; p=0.019), particularly in patients who followed the Mediterranean diet. These findings suggest that monitoring neutrophils can help prevent the development of T2DM, as a reduction in neutrophil counts could be associated with improved insulin sensitivity. Following a Mediterranean diet might be a potential strategy to reduce the incidence of T2DM by lowering neutrophil levels. Further research is necessary to gain a deeper understanding regarding this mechanism.

Prophylactic Antimicrobials for Prevention of Febrile Neutropenia in Tumour-Bearing Dogs Treated With Lomustine.

CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosurea), lomustine, is an oral alkylating agent in the nitrosourea subgroup. The dose-limiting toxicity of CCNU is neutropenia most frequently documented 7 days after its administration. Use of prophylactic antimicrobials to prevent chemotherapy-related febrile neutropenia (FN) and its associated morbidity and mortality has been well-documented in human oncology, but this information is limited in the veterinary literature. The purpose of this multi-institutional retrospective study was to assess whether antimicrobial prophylaxis reduced the risk of FN approximately 7 days after CCNU administration in tumour-bearing dogs. A secondary goal was to identify risk factors for fever development in neutropenic dogs. Two hundred dogs were included in the study. One hundred and fifty-three dogs (76.5%) were neutropenic at the first post-CCNU recheck. One hundred and six (69.3%) dogs received prophylactic antimicrobials and 47 (30.7%) did not. Of the 106 dogs on prophylactic antimicrobials, 8 (7.5%) developed FN. Of the 47 dogs in the no-prophylactic antimicrobials group, 4 (8.5%) developed FN. Use of prophylactic antimicrobials did not reduce the risk of development of FN (p = 0.84). Older age (> 9 y), lower weight and body surface area, and pre-treatment with chemotherapy or radiation therapy were significantly associated with development of FN (p = 0.009, p = 0.023, p = 0.015 and p = 0.01). Patients with a lower absolute neutrophil count, and a higher VCOG-CTCAE v2 neutropenia grade were also at an increased risk of developing FN (p = 0.01, p < 0.001). Additional studies may help establish guidelines for antimicrobial prophylaxis in dogs treated with CCNU, especially for those at high-risk for FN.

Diagnostic value of ultrasound for community-acquired pneumonia in children and its correlation with serum PCT level and PCIS.

This study aimed to evaluate the diagnostic value of ultrasound for community-acquired pneumonia (CAP) in children. Clinical information of children diagnosed with CAP and a control group of healthy children was collected, and lung ultrasound detection was performed. The lung ultrasound score (LUS) was assessed, and venous blood samples were collected. Serum indexes, including white blood cell count, were analyzed using an automatic immunoassay analyzer, while serum procalcitonin (PCT) level was measured using an enzyme-linked immunosorbent assay. The pediatric critical illness score (PCIS) was also performed for all subjects. White blood cell count, absolute neutrophil count, and respiratory index were significantly higher in the CAP group than those in the control group, while the oxygenation index was markedly lower. Ultrasound detection results showed that the CAP group exhibited significantly higher detection rates of pleural effusion, interstitial lung changes, lung consolidation, B-lines, air bronchogram signs, and reduced or absent lung sliding signs compared with the control group. In addition, the LUS and PCT levels were markedly higher in the CAP group, while the PCIS was notably lower. Further analysis exhibited that the LUS in the CAP group was significantly positively correlated with PCT levels and negatively correlated with PCIS. The receiver operating characteristic curve indicated that the area under the curve of LUS for diagnosing children with lung infection was 0.841. LUS is closely related to serum PCT level and PCIS. Lung ultrasound detection demonstrates high sensitivity and specificity, indicating its valuable clinical diagnostic utility for CAP in children.

Real world comparison of filgrastim to filgrastim-sndz in patients with chemotherapy-induced neutropenia.

There exists some apprehension by prescribers, healthcare providers, and other stakeholders regarding the real-world safety and effectiveness of biosimilars. While some of the apprehension is likely due to clinician knowledge gaps in the biosimilarity exercise, additional data (including those generated from the real-world) regarding safety and efficacy could reduce a clinician's perception of biosimilar uncertainty and can potentially increase biosimilar acceptance and uptake. The published literature is lacking regarding the real-world impact on healthcare costs and clinical outcomes when a single healthcare institution converts from filgrastim to filgrastim-sndz as its short-acting Granulocyte Colony Stimulating Factor (GCSF), especially within diverse populations and indications not explicitly studied through the registration trials. Specifically, both filgrastim and filgrastim-sndz possess FDA-approved indications within patients with hematologic malignancies receiving high-dose chemotherapy and in those undergoing bone marrow transplantation. As a biosimilar to filgrastim, the FDA did not require prospective, randomized controlled trials to obtain these indications for filgrastim-sndz. The purpose of this study is to describe real-world healthcare resource costs, utilization patterns, and clinical outcomes in patients with hematologic malignancies who received filgrastim-sndz or filgrastim to support neutrophil recovery following chemotherapy (i.e., induction or consolidation) or a bone marrow transplant (BMT) at Yale New Haven Hospital (YNHH). A total of 148 patients were identified and met the following criteria: at least 18 years old, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, absence of fever or infection, newly diagnosed acute myeloid leukemia or newly post-bone marrow transplant and received filgrastim-sndz (Zarxio®) or reference filgrastim (Neupogen®). Healthcare resource utilization outcomes were compared between biosimilar and reference filgrastim using descriptive statistics. There were no major differences between either cohort, including duration of hospitalization, the number of overall emergency room visits and additional hospital admissions with a primary diagnosis of febrile neutropenia or neutropenia within 30 days post-discharge from initial hospital admission, time to neutrophil recovery following GCSF support, and the incidence and duration of both fever and febrile neutropenia. The total cost based on treatment of all patients in each arm differed significantly with filgrastim-sndz being the most cost-effective choice. filgrastim-sndz significantly reduced healthcare utilization costs compared to reference filgrastim with similar effect on absolute neutrophil count, incidence of fever, and febrile neutropenia.

Relationship Between White Blood Cell Count and Bacteremia Using Interval Likelihood Ratios in Hospitalized Patients.

Patients with bacteremia often have elevated white blood cell (WBC) and neutrophil counts, yet these alone are poor predictors of bacteremia. Data on the continuous relationship between WBC response and bacteremia are lacking. This study aims to characterize the relationship of WBC count, neutrophil percentage, and absolute neutrophil count (ANC) to bacteremia using interval likelihood ratios (ILRs) derived from a large sample of hospitalized patients. Retrospective cohort study in a large healthcare system from 2017 to 2018. This study included non-surgical inpatients who had at least one complete blood count (CBC) with differential up to 24hours after admission and a blood culture. Patients with immunosuppression and malignancy or who received antibiotics before negative blood cultures were excluded. Predictors were WBC count, ANC, and neutrophil percentage. The outcome was bacteremia. We compared test discrimination using the area under the receiver operating characteristics curve (AUROC). We calculated ILRs for bacteremia across test value intervals. As a practical example, we assumed a 5% pre-test probability of bacteremia and calculated the post-test probability for each interval. We compared this approach to a threshold approach using a threshold of 70% neutrophils. Of 25,776 patients with a CBC with differential and blood culture, 1160 had bacteremia. AUROC was highest for neutrophil percentage (0.74), followed by ANC (0.63) and WBC count (0.58). Probability of bacteremia increased exponentially from neutrophil percentage 80 to 100%. Odds of bacteremia varied 35-fold based on neutrophil percentage. A threshold approach with a cut-off of 70% significantly underestimated bacteremia risk at higher levels. ILRs offered a more discriminating approach to estimating the probability of bacteremia than a single threshold. Physicians assessing risk of bacteremia should pay attention to the magnitude of abnormality because very high and very low values have much stronger predictive power than dichotomized results.

One size does NOT fit all – factoring weight into current stem cell transplant guidelines in multiple myeloma patients

Abstract Autologous hematopoietic stem cell (HPSC) transplantation serves as the standard of care treatment for multiple myeloma patients. The standard ASCT procedures for multiple myeloma (MM) patients often includes induction therapy, stem cell collection via apheresis and autologous hematopoietic cell transplantation (HCT) for eligible patients. The current guideline for HPSC collection for multiple myeloma established that 3x106 cells/kg of actual body weight (ABW) by the 1997 study of stem cell transplants in breast cancer. Recent research indicates that ideal body weight (IBW) utilization is a stronger predictor of post-autotransplantation neutrophil recovery than calculations based on ABW. Reducing the cost of HPSC collection and cryopreservation is critical to mitigate the cost incurred by the transplant center and the patient. This study evaluates whether using a patient’s IBW or Adjusted Ideal Body Weight (AIBW) would be satisfactory in determining the amount of stem cells required for transfusion when compared to ABW. After institutional review board approval, a retrospective chart review study analyzed a cohort of 224 deceased MM patients, who received HCT at the UAB Medicine Hospital within the fiscal years of 2017 to 2019. The ABW for each patient was used to calculate their IBW and AIBW using the formulas shown below. The target CD34+ cell amount for patients was calculated using each body weight parameter. The platelet count and absolute neutrophil count (ANC) defined a successful platelet and neutrophil engraftment. The engraftment date was determined as the day the platelet value exceeded 20 and ANC exceeded 0.5 for three consecutive days (without any transfusion within a seven day window) and a statistical analysis was utilized to determine whether the IBW and AIBW parameters were adequate to achieve successful engraftment and HCT. This study finds that the cohort of multiple myeloma patients are significantly more overweight than the prior study that established the current guidelines for autologous hematopoietic cell transplantation. The results for CD34+/kg cell targets for ideal and adjusted ideal body weight suggests that there are minimal differences in platelet and neutrophil engraftment and number of platelet transfusions when compared to CD34+/kg targets using actual body weight. Some methods to reduce excessive stem cell collection include decreasing target cell dosage from previous standards of 6.0 x 106 cells/kg or calculating total cell dosage with IBW or AIBW instead of ABW. Future studies should evaluate the efficacy of cell dosage decrease to lowered targets and total cell calculations using IBW or AIBW instead of ABW. Equation 1. ABW to IBW Conversion (H = height over 5 ft. in inches) IBW(males) = 50 kg + (2.3 kg x H) IBW(females) = 45.5 kg + (2.3 kg x H) Equation 2. ABW to AIBW Conversion AIBW = IBW + 0.5(ABW-IBW)

Plasma Cell Leukemia with atypical CCND1/IGH fusion and Monocytoid morphology; A Rare Case Finding

Abstract Introduction/Objective Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia, often presenting as a variant of multiple myeloma (MM). It is characterized by the presence of ≥5% circulating plasma cells in peripheral blood, either as a primary or secondary manifestation of MM. Methods/Case Report Our case is of a 77-year-old male who presented with epigastric tenderness and bi-basilar crackles. Laboratory results showed severe hypercalcemia, elevated creatinine, leukocytosis, and elevated absolute neutrophil and lymphocyte counts. Imaging revealed widespread lytic lesions in the ribs, scapulae, thoracolumbar spine, and bony pelvis. Peripheral blood smear showed significant macrocytic anemia with rare polychromatophilic cells, numerous immature plasmacytoid cells (&amp;gt;20% of total cell count) and monocytoid morphology. Flow cytometry confirmed a population of monotypic plasma cells (28% of total cells). Bone marrow biopsy revealed a hypercellular plasma cell infiltrate with complex clonal karyotypic abnormalities, including the t(11;14)(q13;q32), rearrangements of 1p, and gain of 1q. FISH analysis showed an atypical CCND1/IGH fusion in 57% of cells, with one fusion, two orange (CCND1), and two green (IGH) signals. The case presented demonstrates a rare instance of an atypical CCND1/IGH fusion in plasma cell leukemia with monocytoid morphology, which poses diagnostic challenges. Prompt and accurate diagnosis is essential for managing the condition, given its consistently poor prognosis despite advancements in therapy over the past decade. Results (if a Case Study enter NA) NA Conclusion Our case highlights the importance of recognizing rare molecular abnormalities in PCL and suggests that further research into the molecular pathways involved in the disease is needed to improve diagnosis, treatment options and clinical outcomes.

Severe myelotoxicities related to Th1, Th2, Th17 and Treg CD4+ T cells subpopulations and their cytokine profiles in Mexican children with acute lymphoblastic leukemia during induction of chemotherapy

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer in the world, and the myelotoxicities due to chemotherapy can lead to severe infections and hemorrhages with high morbidity and mortality. The immune response has implications in the severity of cancer or survival. This immune response is associated with the predominant subpopulations CD4+ T cells and their effector cytokines. However, it is not known if the immune responses are associated with severe myelotoxicities and mortality in children with ALL. Methods To evaluate the contributions of immunological factors on ALL severe myelotoxicities, we identified the Th1, Th2, Th9, Th17, Th22 and Tregs subpopulations of CD4+ T cells according to their chemokine receptor expression patterns in peripheral blood mononuclear cells by flow cytometry. We evaluated also their cytokines levels by Milliplex in serum from 10 children with ALL at diagnosis (day 0), during induction (day 19) and at the end of induction (day 30) between April 2022 and July 2023. Clinical characteristics such age, sex, type and risk of ALL, hemoglobin and platelets levels, absolute neutrophil count, grade of severity and type of myelotoxicities, infections, and hemorrhages were collected. Clinical outcomes as hospitalization care requirements, ICU admission, leukemia remission or relapsed and mortality were followed and documented. Results The age of children was 8.9 years, (SD,5.6; range 2-16), 60% were male sex, all children had pre- B ALL diagnosis, and 80% were intermediate risk-ALL. Th1 cells were predominant at diagnosis (8.1%) and at the end of induction (7.8%), and Th2 cells at day 19 (7.4%), whereas Th17 were significantly decreased at day 30 (2.6%) (p&amp;lt;0.05). Four patients presented bloodstream infection, two by Gram-positive bacteria (Micrococcus, and Streptococcus), one by Klebsiella pneumoniae antimicrobial resistant, and one by Trichosporum asahii. Severe myelotoxicities were presented in 20% of the patients at day19, and in 30% at day 30. Remission was documented in all patients at day 30 and one was identified with early relapse in the follow-up. Three patients (30%) presented poor outcomes, requiring care in ICU and one died (10%) due to fungal infection. Treg cells were significantly predominant in the children who died by fungal infection (p&amp;lt;0.05), with IL-10 level of 84.6 pg/mL but not detectable IL-35 levels. Conclusion Th17 and Treg subpopulations of CD4+ T cells can play an essential role in immune microenvironment during induction related with the severity of the myelotoxicities and infections, and cytokine IL-10 could be used as marker of infection outcome.

Clinical Characteristics, Management, and Outcomes of Bacteremia in Children with Cancer: A Retrospective Study

Abstract Background Bacteremia is a common infectious complication among pediatric oncology patients, yet management practices are not standardized. Antibiotic treatment courses as short as seven days are supported by literature and could improve patient quality of life and resource use. However, it is not known if short courses are associated with greater treatment failure in immunocompromised patients. Methods We conducted a retrospective study at St. Jude Children’s Research Hospital, including patients with a laboratory confirmed bloodstream bacterial infection between April 1, 2022, and March 31, 2023. Clinical characteristics such as age, gender, type of malignancy, phase of treatment, underlying chronic conditions, and clinical sites of infection were collected. Antibiotics used, duration of therapy, and route of administration were also gathered to examine clinical management. Clinical outcomes were measured by documenting ICU admission, oxygen, fluid and vasopressor requirements, date of hospital discharge, bacteremia recurrence, and mortality. Results 86 patients contributed 112 bacteremia episodes that met eligibility criteria. Severe neutropenia was present at onset in 68% of all episodes and 32% of patients did not have neutrophil recovery over 500 cells/ml during the episode. Gram-negative organisms accounted for 52% of isolated organisms, with the most common organisms isolated overall being Escherichia coli (19%), followed by Klebsiella pneumoniae (14%), and Viridans group streptococcus (14%). The median length of antibiotic treatment was 12 days. Treatment duration was not associated with oncologic diagnosis or Gram-negative versus Gram-positive infection. Conclusion Bacteremia occurs more frequently in patients who are neutropenic, especially those who are severely neutropenic with an absolute neutrophil count less than 500 cells/mL. Treatment duration is not associated with primary cancer diagnosis or type of bacteremia. In this single high resource setting, bloodstream infections resulted in significant morbidity, resource use, and a mortality rate of 8%, highlighting opportunities for investigation to improve clinical practices.

Outcomes of severe lower respiratory tract infection in Mexican children with cancer

Abstract Background Lower respiratory tract infections (LRTI) are a very serious complication in children with cancer, with high morbidity and mortality, due to viral infections, followed by bacterial and fungal organisms. These patients with cancer are undergoing chemotherapy that damages their mucosal barrier and respiratory epithelium, and course with profound or severe neutropenia. Thus, they are high-risk to develop severe respiratory infections acquired from the community. However, the clinical characteristics, etiological agents, finding on computed tomography (CT) and outcomes of the LRTI in immunocompromised patients are not well known, these are necessary in order to start adequate management including empirical antimicrobial therapy and supplementary oxygen therapy. Methods Children with cancer who were attended in the pediatric emergency room due to fever (&amp;gt;38°C) and presence of respiratory symptoms such as increased breath rate, cough, O2Sat &amp;lt;93%, and needed to supplementary oxygen were included. To analyze the cases of children with cancer and LRTI we documented the data regarding to clinical presentation, detection of respiratory virus and findings in the CT. Data such age, sex, oncological diagnosis, absolute neutrophil count. The detection of nucleic acid of respiratory virus was performed by qPCR, whereas the identification galactomannan in serum was done for fungal diagnosis, and clinical presentation was initial used for diagnosis of bacterial LRTI. The findings on TC were included to integrate all the LRTI etiological diagnosis. The outcomes recorded were to need supplementary oxygen therapy (nasal cannula, high-flow nasal cannula or mechanical ventilation), ICU admission, and mortality on the follow for all patient included in the study. A descriptive statistical analysis was performed to estimate frequency of the etiological agents, outcomes, and mortality rate. Results A total of 10 children with cancer and severe LRTI were followed up, 60% female sex, age 5.5 years (range, 1-16 &amp;lt;); 80% had acute leukemias and 20% lymphoma. Seven (70%) children were diagnosed with bacterial LRTI, whereas two (20%) and one (10%) were viral LRTI-diagnosed. The finding in the CT were the follow: bilateral patchy consolidation and ill-defined small nodules for viral infection, centrilobular nodules and bronchial wall thickening for bacterial infection and scattered nodules or patchy focus for fungal infection. In respect to clinical presentation 90% had fever, 100% had cough, and 100% had O2Sat &amp;lt;93%. Of these patients 60% were presented with profound and 20% with severe neutropenia (p&amp;lt;0.05); 30% had required high-flow oxygen and 10% mechanical ventilation; and three (30%) patients required care in ICU. The mortality rate for severe LRTI was 30%. Conclusion Children with cancer and profound or severe neutropenia are in high-risk to develop severe LRTI and they have high mortality. The finding on the CT can help to start on adequate management for LRTI in immunosuppressed pediatric patients.

Plasma Cell-free DNA Metagenomic Next-Generation Sequencing in Immunocompromised Children

Abstract Background Plasma cell-free DNA metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool for infectious diseases [1]. Data suggests that plasma mNGS may be useful in immunocompromised adults, changing management in up to 60% of the patients [2]. A prospective study evaluating utility of plasma mNGS for pneumonia in immunocompromised adults concluded that mNGS provided an additive diagnostic value of 12.1% [3]. A similar study in adults with febrile neutropenia reported a sensitivity and specificity of 85 and 100%, respectively [4]. However, there is limited data evaluating the utility of mNGS in immunocompromised children. Methods We retrospectively reviewed all pediatric immunocompromised patients who had plasma mNGS testing performed from December 2018 to July 2023 at St. Jude Children’s Research Hospital. Electronic medical records were reviewed to extract relevant clinical data and microbiologic data including results of mNGS, contemporaneous cultures, and related antimicrobial treatment. Descriptive statistics are presented as frequencies and medians (interquartile range, IQR). Comparisons were performed using Fisher’s exact test or Wilcoxon rank-sum test, as appropriate, using R version 3.6.3. Results A total of 18 immunocompromised children underwent plasma mNGS testing. Acute lymphoblastic leukemia was the most common malignancy (33.3%), followed by acute myeloid leukemia (22.2%). Two patients (11.1%) had undergone hematopoietic cell transplant, both allogeneic. At the time of testing, 16 patients (88.9%) had fever and 10 (55.6%) had an absolute neutrophil count of &amp;lt;500/mm3. All except one were on antimicrobial therapy at the time of testing, with a median duration of 8 days (IQR=12.25). Only 9 (50%) patients had a positive mNGS result. A positive mNGS resulted in broadening or extending antibiotics course in 4 patients (22.2%); negative mNGS results did not lead to changes in management in any of the cases. There were no significant differences in age, sex, days of fever, neutropenia, gastrointestinal (GI) symptoms, and days of fever before testing between those with positive versus negative results. However, a higher frequency of GI symptoms at the time of testing among those with positive results was observed. Clinical characteristics and impact on management in patients with positive and negative results are summarized in Table 1. Conclusion Plasma mNGS had a limited impact on the management of immunocompromised children at our institution. Negative results did not lead to de-escalation of therapy, and positive results led to additional exposure to antibiotics. Further research is needed to determine the role of mNGS in this population, and the interpretation of positive testing in the setting of gastrointestinal disease.

Comparison of clinical and laboratory characteristics of COVID-19 and influenza in hospitalized children.

COVID-19 and influenza infections have similar modes of transmission and clinical symptoms but have different prognoses and treatment methods; therefore, it is important to make a final diagnosis. Herein, we aimed to compare the demographic, clinical, and laboratory differences in hospitalized pediatric patients with COVID-19 and influenza. This retrospective study comprised patients with COVID-19 managed between March 2020 to February 2022, and patients with influenza managed between December 2017 to February 2022, at a tertiary care hospital. The clinical data and laboratory parameters were obtained from the medical records of the hospital. Pediatric intensive care unit (PICU) admission, need for oxygen support, and the mortality rates of the patients were recorded and compared statistically. Overall, 107 patients with COVID-19 and 250 patients with influenza were included. Underlying chronic disease (UCD) rates were statistically higher in patients with COVID-19 (p < 0.001). When the symptoms were compared, fever, cough, and runny nose were more common in patients with influenza, and abdominal pain and rash were more common in patients with COVID-19 (p < 0.05). In patients with influenza, white blood cell count and absolute neutrophil count values were lower (p = 0.021 and p = 0.037, respectively), and aspartate aminotransferase and creatinine kinase values were higher (p = 0.007 and p < 0.001, respectively). PICU admission rates and oxygen support needs were similar in both groups (p > 0.05). When the virus was COVID-19, it had 7.8 times higher risk of mortality compared to influenza (p = 0.002). There were statistically significant risk for mortality when the virus was COVID-19, the risk of mortality was 6.9 times higher in those with UCD, 8.5 times higher in those with admission to PICU and 3.8 times higher in those with needing mechanical ventilation (MV) compared to when the virus was influenza (p = 0.004, p = 0.006 and p = 0.049, respectively). The mortality rate was higher in patients with COVID-19 (p = 0.007). This study showed that COVID-19 might negatively affect the survival times and increase mortality rates, especially in children with an UCD, admitted to the PICU and in need of MV.

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.