Absolute Neutrophil Count Research Articles

Safety and efficacy of amulirafusp alfa (IMM0306), a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a phase 1/2 study

BackgroundAmulirafusp alfa (IMM0306) is a fusion protein of CD47 binding domain of signal-regulatory protein alpha (SIRPα) with CD20 monoclonal antibody on both heavy chains. This study aimed to evaluate the safety and preliminary efficacy of amulirafusp alfa in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).MethodsWe enrolled patients with CD20 + r/r B-NHL who had previously received at least two lines of therapy to receive a single-dose of amulirafusp alfa in the first 2 weeks, followed by a multiple-dose period, in which the patients received the same intravenous dose every week in 4-week cycles. The primary endpoints were to evaluate the safety, determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of amulirafusp alfa.ResultsBetween May 22, 2020 and February 10, 2022, 48 patients with r/r B-NHL were enrolled and received amulirafusp alfa at the doses of 40–2000 μg/kg. As of the data cut-off date of April 18, 2024, no dose-limiting toxicity was observed, and the MTD was not reached. The dose of 2000 μg/kg was identified as the RP2D. All grades and ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 48 (100%) and 33 (68.8%) patients, respectively. The most common ≥ grade 3 TRAEs were lymphocyte count decreased (28/48, 58.3%), white blood cell count decreased (10/48, 20.8%), absolute neutrophil count decreased (9/48, 18.8%) and anemia (5/48, 10.4%). At the doses of 800–2000 μg/kg, objective response rate in follicular lymphoma and marginal zone lymphoma was 41.2% (7/17, 95% confidence interval [CI] 18.4–67.1) and 33.3% (2/6, 95% CI 3.7–71.0), respectively.ConclusionAmulirafusp alfa showed favorable safety profile and preliminary efficacy in patients with r/r B-NHL, meriting further investigation.Trial registration NCT05805943.

Neutropenia and Felty Syndrome in the Twenty-First Century: Redefining Ancient Concepts in Rheumatoid Arthritis Patients

Objectives: To describe the frequency of neutropenia and Felty syndrome in patients with rheumatoid arthritis (RA) attended in routine clinical practice. Methods: We selected by randomization a sample of 270 RA patients attended from January 2014 to November 2022. Demographic, clinical, and neutropenia-related variables were collected from the electronic medical records. Neutropenia was defined as having an absolute neutrophil count (ANC) of less than 1500/mm3 once, and acute if it persisted for <3 months. Felty syndrome was defined as RA-related neutropenia, rheumatoid factor (RF) and/or anti citrullinated protein antibody (ACPA) positivity. Results: We found 50 patients who had at least one neutropenia episode, with an incidence of 18.5% (14.0–25.6%). Most were women, with age (mean, p25–p75) at the time of neutropenia of 61.5 (57.4–69.3) years, 85% RF+ and 76% ACPA+. The demographic and RA characteristics of patients with and without neutropenia were very similar, except for sex: most patients with neutropenia were women. The 50 patients had 99 episodes of neutropenia; 59% were acute. The lower ANC was 1240 (1000–1395) mm3, and most of the episodes were mild (74%). In 32% of cases, there was other cytopenia. The RA activity measured by DAS28 in patients with neutropenia was low, at 2.18 (1.75–2.97). A total of 82 of 99 neutropenia episodes were related to DMARDs, 60% to Anti-IL6 drugs in monotherapy, 13% to RA activity, 3% to infectious diseases and 1% to hematologic malignancy. There were five (1.8%) cases with Felty syndrome, but only one woman with the classic combination of RA, positivity of autoantibodies (RF and ACPA), neutropenia and splenomegaly. Conclusions: In the 21st century, neutropenia in RA patients is most commonly related to biologics, mostly IL6 inhibitors and methotrexate. Episodes are mild, acute, with low RA activity, and associated with severe infections in few cases. Felty syndrome is rare.

Novel immunoinflammatory blood markers in Graves’ orbitopathy: insights into activity and severity

ObjectiveThis prospective case–control study examined the novel immunoinflammatory markers obtained from blood counts of patients with Graves’ orbitopathy (GO), Graves’ disease (GD) and healthy subjects.MethodsDemographic data, white cell count parameters,...

Development and validation of predictive models of early immune effector cell-associated hematotoxicity (eIPMs).

Immune effector cell-associated hematotoxicity (ICAHT) is associated with morbidity and mortality after chimeric antigen receptor (CAR) T-cell therapy. To date, the factors associated with ICAHT are poorly characterized, and there is no validated predictive model of ICAHT specifically. Therefore, we performed comprehensive univariate analyses to identify factors associated with severe (grade 3-4) early ICAHT (eICAHT) in 691 patients who received commercial or investigational CAR T-cell therapy for hematologic malignancies. In univariate logistic regression, pre-infusion factors associated with severe eICAHT included disease type (acute lymphoblastic leukemia), pre-lymphodepletion (LD) blood counts including absolute neutrophil count (ANC), lactate dehydrogenase (LDH), and inflammatory (C-reactive protein [CRP]; ferritin, interleukin-6 [IL-6]), and coagulopathy biomarkers (D-dimer). Post-infusion laboratory markers associated with severe eICAHT included early and peak levels of inflammatory biomarkers (CRP, ferritin, IL-6), coagulopathy biomarkers (D-dimer), peak cytokine release syndrome (CRS) grade, and peak neurotoxicity grade. We trained (n = 483) and validated (n = 208) two Early ICAHT Prediction Models (eIPM): eIPMPre including pre-infusion factors only (disease type and pre-LD ANC, platelet count, LDH, and ferritin) and eIPMPost containing both pre- (disease type and pre-LD ANC, platelet count, and LDH) and post-infusion (day +3 ferritin) factors. Both models generated calibrated predictions and high discrimination (area under the receiver operating characteristic curve [AUROC] in test set: 0.87 for eIPMPre and 0.88 for eIPMPost), with higher net benefit in decision curve analysis for eIPMPost. Individualized predictions of severe eICAHT can be generated from both eIPMs utilizing our online tool (available at https://eipm.fredhutch.org).

Combination Therapy with Korean Medicine and Filgrastim on Neutropenia: A Retrospective Study

Objectives: Neutropenia is a complication due to chemotherapy or radiotherapy that can limit clinical outcomes. Previous systematic reviews and meta-analysis have suggested that traditional Asian medicine may relieve neutropenia. This study investigated the effect of the combination therapy of Korean Medicine (KM) and filgrastim on neutropenia.Methods: A total of 336 subjects were included, with 167 in the only filgrastim treatment group and 169 in the filgrastim with KM treatment group. Absolute neutrophil count (ANC) was calculated by multiplying the white blood cell count by the total percentage of neutrophils. ANC was observed on the day of filgrastim and up to 6 days with hospital medical records.Results: The clinical characteristics of the participants in the filgrastim with KM treatment group tended to have higher age. Comparing the two groups, by the linear mixed-effects model, ANC mean was significantly different on the 3rd day. A linear mixed effect model was performed to estimate difference in slope of ANC over time after treatment between the two groups. The slope difference was significant in neutropenia grade 3 patients. The mean of ANC increment after initial treatment tends to increase with the number of days of KM treatment but not statistically significant. During the follow-up period, the average blood levels of patients in the filgrastim with KM treatment group were within the normal range.Conclusions: The combination treatment with filgrastim and KM can be effective for patients with neutropenia.

Evaluation of Inflammatory Status in COVID-19 Patients with Chronic Kidney Disease: A Comparative Analysis Based on Creatinine Clearance Levels

Background and Objectives: Patients with chronic kidney disease (CKD) are at increased risk of severe COVID-19 outcomes due to their compromised immune systems and chronic inflammatory state. This study aimed to evaluate and compare the inflammatory status of COVID-19 patients with CKD, stratified by creatinine clearance (CrCl) levels: CrCl < 30 mL/min, CrCl 30–60 mL/min, and CrCl > 60 mL/min. Multiple inflammatory scores combining laboratory parameters were assessed, including novel scores and established indices. Methods: In this retrospective cohort study, 223 patients admitted with confirmed COVID-19 were included and divided into three groups based on CrCl levels: CrCl < 30 (n = 41), CrCl 30–60 (n = 78), and CrCl > 60 (n = 104). Laboratory parameters including C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), ferritin, platelet count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and serum albumin were collected. Multiple inflammatory scores were calculated, including inflammation scores (IS1–IS4), the systemic inflammatory index (SII), the C-reactive protein-to-albumin ratio (CAR), the lymphocyte-to-C-reactive protein ratio (LCR), and the prognostic nutritional index (PNI). Statistical analyses were performed to compare inflammatory scores among groups and assess correlations with clinical outcomes. Results: The CrCl < 30 group exhibited significantly higher levels of inflammatory markers and inflammatory scores compared with the other groups (p < 0.001). Among the additional scores, CAR and SII were significantly elevated in patients with lower CrCl levels, while LCR and PNI were decreased. CAR showed a strong positive correlation with COVID-19 severity (r = 0.65, p < 0.001), and PNI was inversely correlated with mortality (r = −0.58, p < 0.001). Multivariate regression analysis indicated that lower CrCl levels, higher IS3 and CAR, and lower PNI were independent predictors of severe COVID-19 outcomes. Conclusions: CKD patients with lower CrCl levels have an amplified inflammatory response during COVID-19 infection, as evidenced by elevated inflammatory scores. The additional inflammatory scores, particularly CAR and PNI, may serve as valuable tools for risk stratification and management of COVID-19 in CKD patients. Early identification of patients with high CAR and low PNI could improve clinical outcomes through timely therapeutic interventions.

Venetoclax plus D-CAG (decitabine, cytarabine, aclarubicin, G-CSF) for elderly or unfit patients with newly diagnosed acute myeloid leukemia: a multicenter, prospective study.

Induction regimens with satisfactory remission rates are limited for patients with acute myeloid leukemia (AML) who are elderly or ineligible for intensive chemotherapy. This study is a single-arm, multicenter, prospective phase I/II study (registered with the Chinese Clinical Trial Registry as ChiCTR 2200059694 on May 8, 2022), aiming to evaluate the efficacy and safety of venetoclax plus decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (VD-CAG) for newly diagnosed AML patients who are elderly or ineligible for intensive chemotherapy. The primary endpoint was composite complete remission (CRc) after 1 cycle of induction chemotherapy. The secondary endpoints were measurable residual disease (MRD) by flow cytometry and adverse events. Forty patients(n = 40) received 1 cycle of the VD-CAG regimen for induction chemotherapy. The median age of the patients was 64 (55-81) years, and 10 patients (25%) had secondary AML. Our results showed that 1 cycle of VD-CAG had a high overall response rate of 97.5% and CRc of 95%, and all 10 patients with secondary AML achieved CRc. Moreover, the patients who achieved CRc had deep remission, with MRD-negativity of 71.1% and 54.2% by flow cytometry and molecular assessment, respectively. In addition, blood cell recovery was quick, with a median time to absolute neutrophil count ≥ 1.0 × 109/L and platelet count ≥ 100 × 109/L at 19 days and 15.5 days, respectively. In conclusion, VD-CAG demonstrates high efficacy as an induction treatment for elderly or unfit patients with newly diagnosed AML, and it could be an alternative upfront therapy for this subpopulation, Trials with large-scale subjects are needed for further validation, especially for secondary AML.

Navigating the Diagnostic Maze: A Case Report of Uncommon Cardiac Metastasis in Childhood Ewing Sarcoma

AbstractEwing sarcoma is a bone cancer affecting children and young adult males. It usually presents as a single bone tumor, but it can also occur in multiple locations. Nevertheless, Ewing sarcoma is an extremely aggressive tumor capable of metastasizing to other parts of the body, such as the lungs, bones, liver, and lymph nodes. Cardiac metastases are rare, indicating a poor prognosis, as they suggest that the cancer has become more advanced and challenging to treat.This case report describes a 9-year-old boy who presented with complaints of fever and multiple swellings in the calvaria, periorbital region, clavicle, and left thigh. Laboratory investigations revealed a high erythrocyte sedimentation rate, elevated absolute neutrophil count, high phosphate and calcium levels, and low magnesium levels. Computed tomography imaging revealed the presence of multifocal osseous expansile lytic lesions, multiple pulmonary metastases, and extensive soft tissue involvement of the heart. Based on these findings, possible differential diagnoses of Langerhans cell histiocytosis, lymphoma, and Ewing sarcoma were considered. Further histopathological examination and immunohistochemistry confirmed a final diagnosis of metastatic Ewing sarcoma.The most common metastasis sites for Ewing sarcoma are the lungs, with rare occurrences in the central nervous system, and metastasis to the heart is uncommon. We present here a rare undiagnosed Ewing sarcoma with cardiac metastasis, in addition to pulmonary and multifocal osseous metastasis. This case is unique because multifocal osseous involvement is rare and further lung and heart involvement is even rarer in Ewing sarcoma.

Soluble CD206 and CD163 as novel prognostic biomarkers in adult acute myeloid leukemia

BackgroundDespite advances in chemotherapy, the prognosis of adult acute myeloid leukemia (AML) patients remains poor, with a 5-year survival rate below 25%. In the tumor microenvironment of AML, tumor-associated macrophages (TAMs) are very important in the microenvironment of AML tumors because they help leukemic cells to survive, grow and migrate. They also play a key role in how the disease progresses. M2 macrophages highly express both CD206 (mannose receptor, C type I, and CD163 (hemoglobin scavenger receptor), a monocyte/macrophage receptor, as markers for M2 macrophages. Soluble CD206 (sCD206) and CD163 (sCD163) emerge as prognostic players for hematopoietic neoplasms. This study aimed to assess the prognostic potential of sCD206 and sCD163 as serological markers in AML. The study included 60 AML patients and 20 healthy volunteers as controls. The levels of serological markers sCD206 and sCD163 were measured by ELISA, and their prognostic values were evaluated.ResultsSerum levels of sCD206 and sCD163 were statistically significantly (P < 0.001) higher in AML cases than in controls. AML patients were categorized into two subgroups based on the response outcome to induction therapy: 36 patients (60%) had complete response (CR), and the other 24 patients (40%) had refractory disease. Interestingly, based on response outcome, serum levels of sCD206 and sCD163 as well as total leukocytic count (TLC), absolute neutrophils count (ANC) and absolute lymphocyte count (ALC) were significantly higher (all P < 0.001) in refractory group than in CR group. Further, a significant positive correlation of both sCD206 and sCD163 with TLC, ANC and ALC was observed (all P < 0.001).ConclusionLevels of sCD206 and sCD163 emerge as promising prognostic biomarkers for AML outcome and progression.

Clinical and Genetic Markers of Vascular Toxicity in Glioblastoma Patients: Insights from NRG Oncology RTOG-0825.

Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment. 591 Non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N=367) by occurrence of thrombosis or hypertension (grade ≥2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the clinical model as a single nucleotide polymorphism (SNP) -dose effect variable to produce the final genetic models. Thrombosis and hypertension were experienced by 62 (11%) and 59 (10%) patients, respectively. Patients who experienced hypertension displayed improved survival over those without hypertension (median overall survival: 25.72 vs 15.47 months, p=0.002). The genetic model of thrombosis included corticosteroid use (OR: 7.13, p=0.02), absolute neutrophil count (OR: 1.008, p=0.19), body surface area (OR: 18.87, p=0.0008), and the SNP-dose effect (3 variants; OR: 3.79, p<.0001). The genetic model of hypertension included bevacizumab use (OR: 0.97, p=0.95) and the SNP-dose effect (6 variants; OR: 4.44, p<.0001). In this study, germline variants were superior in predicting hypertension than clinical variables alone. Additionally, corticosteroid use was a considerable risk factor for thrombosis. Future investigations should confirm the hazard of corticosteroid use on thrombosis and the impact of bevacizumab in other malignancies after accounting for the genetic risk of hypertension.

Prognostic factors of immunosuppression therapy combined with eltrombopag in the treatment of childhood severe aplastic anemia

Objective: To analyze the influence factors on the efficacy of immunosuppression therapy (IST) combined with eltrombopag and IST alone in the treatment of childhood severe aplastic anemia (SAA). Methods: A retrospective cohort study. A total of 124 children with SAA who were initially treated with IST in Beijing Children's Hospital from March 2017 to May 2020 were enrolled. Clinical characteristics, laboratory examination and prognosis data were collected at the time of enrollment. According to the treatment plan, the children were divided into the eltrombopag combined with IST group (eltrombopag group) and the IST group. Binary Logistic regression model was used to analyze the factors affecting the efficacy of the two groups at 6 months of treatment, and the factors affecting the efficacy of the eltrombopag group at the end of follow-up. Results: There were 75 cases (45 males and 30 females) in the eltrombopag group. The age of diagnosis was 5.9 (3.5, 8.5) years. There were 49 patients in the IST group, including 23 males and 26 females, whose age at diagnosis was 6.2 (4.4, 8.8) years. The absolute lymphocyte count before treatment in the eltrombopag group was significantly lower than that in the IST group (1.1 (0.4, 1.6)×109 vs. 2.1 (1.4, 2.8)×109/L). Absolute reticulocyte count in the eltrombopag group was significantly higher than that of IST group (26.9 (8.7, 54.2)×109 vs. 9.5 (4.0, 19.0)×109/L) (both P<0.05). Influencing factors of 6-month response: a comparison between response and un-response groups in the eltrombopag treated patients showed that, before treatment, hemoglobin (69 (61, 78) vs. 64 (59, 68) g/L), platelet (10 (6, 16)×109 vs. 6 (3, 8)×109/L), absolute reticulocyte count (ARC) (34.0 (15.8, 57.3)×109 vs. 6.5 (4.6, 16.8)×109/L) and the response rate to granulocyte colony stimulating factor (G-CSF) after treatment (82.4% (47/57) vs. 9/18) were significantly different (all P<0.05). Logistic regression model analysis showed that ARC (OR=1.09, 95%CI 1.02-1.18) and absolute neutrophil count were independent influencing factors of 6-month response rate in the eltrombopag group (OR=0.00, 95%CI 0.00-0.89). ARC was also the independent influencing factors of the end of follow-up response rate in the eltrombopag group (OR=1.04, 95%CI 1.01-1.07). Conclusions: Pre-treatment blood count and response to G-CSF were predictors of overall response to eltrombopag combined with IST. The higher the ARC before treatment, the higher the total response rate and complete response.

Application of exchange transfusion in neonates with severe pertussis and hyperleukocytosis

To investigate the efficacy and safety of exchange transfusion in neonates with severe pertussis. A retrospective analysis was performed for the medical data of five neonates with severe pertussis who underwent exchange transfusion in the Department of Neonatology, Hunan Children's Hospital, from August 2019 to March 2024. The clinical characteristics of the patients were summarized, and the efficacy and adverse reactions of exchange transfusion were analyzed. All five neonates had the symptoms of hypoxemia, recurrent apnea, and heart failure and required invasive mechanical ventilation. Two cases of pulmonary hypertension were observed, one of which was complicated by decompensated shock. Before exchange transfusion, the five children had a median leukocyte count of 82.60×109/L, a median absolute lymphocyte count of 28.20×109/L, and a median absolute neutrophil count of 43.10×109/L, and reexamination at 4 hours after exchange transfusion showed that these values decreased to 28.40×109/L, 7.60×109/L, and 15.40×109/L, respectively. The four children who underwent exchange transfusion in the early stage of cardiopulmonary failure showed varying degrees of improvement in oxygenation and a reduction in the partial pressure of carbon dioxide, and they were discharged after improvement; the one child who underwent exchange transfusion in the late stage of cardiopulmonary failure ultimately died. No child experienced severe adverse reactions related to exchange transfusion. For neonates with severe pertussis, initiating exchange transfusion in the early stages of cardiopulmonary failure can effectively reduce leukocyte levels, potentially improve survival rates, and is relatively safe.

Exploring optimal administration timing of pegylated recombinant human granulocyte colony-stimulating factor for chemotherapy-induced neutropenia in early breast cancer treated with pharmorubicin and endoxan: a prospective randomized controlled clinical trial

BackgroundPegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is a treatment for preventing febrile neutropenia (FN) in patients with early breast cancer. However, the optimal injection timing of PEG-rhG-CSF after chemotherapy is obscure. The trial was designed to explore the best administration timing of PEG-rhG-CSF when breast cancer patients could benefit most.MethodsPatients with early breast cancer were randomly assigned to receive a preventive injection on the 7th or 3rd day following chemotherapy. The experimental group (n = 80) received PEG-rhG-CSF treatment on day 7 after chemotherapy, whereas the control group (n = 80) received it on day 3. The occurrence of grades 3–4 neutropenia and FN in the first cycle was the primary endpoint. The secondary endpoint was the frequency of PEG-rhG-CSF dose reduction.ResultsIn comparison to the control group, the experimental group exhibited higher white blood cell count (WBC) and absolute neutrophil count (ANC) on the 9th and 13th days following chemotherapy (P < 0.05). Additionally, the incidence of grade 3–4 neutropenia was significantly lower in the experimental group (P = 0.038). Furthermore, a greater proportion of patients in the experimental group met the criteria for reducing the PEG-rhG-CSF dose compared to the control group (69.74% vs. 35.06%, P < 0.001).ConclusionsIn comparison with PEG-rhG-CSF injection on day 3 after chemotherapy, the incidence of grade 3–4 myelosuppression is lower, and the safety is more manageable after the injection on day 7. This approach potentially allows for a wider adoption of PEG-rhG-CSF dose reduction, leading to a consequential decrease in overall medical costs for patients.Trial registrationClinical Trials: NCT04477616. Registered July 16, 2020.

Abstract 4119517: Association of Systemic Inflammatory Response Syndrome with Cardiovascular Events after Mitral Transcatheter Edge-to-edge Repair

Background: Systemic inflammatory response syndrome (SIRS) following cardiovascular interventions is associated with adverse events during hospitalization and follow-up. Mitral transcatheter edge-to-edge repair (M-TEER) is increasingly utilized for treatment of mitral regurgitation (MR). Hypothesis: It is unknown whether SIRS following M-TEER may occur and be associated with adverse clinical outcomes. Goals: to investigate the frequency and impact of SIRS following M-TEER on major cardiovascular events (MACE) and MR recurrence. Methods: A total of 158 consecutive patients with severe MR undergoing M-TEER were studied. SIRS was defined by leukocytosis (≥12×10 9 /L) and fever (T≥38 °C) within 48 hours after intervention. Baseline inflammation was measured by absolute neutrophil and lymphocyte counts and neutrophil: lymphocyte ratio (NLR). The primary endpoint of MACE was the composite of non-fatal myocardial infarction (MI), non-fatal stroke, and all-cause death. Recurrent MR at follow-up was also recorded. Results: The mean patient age was 80.8±8.8 years. 44 (27.9%) developed SIRS. NLR correlated with onset of leukocytosis and fever (p=0.04). During a median follow-up of 12.5±8.2 months, the primary endpoint occurred in 27 (17.1%) patients (6 MI, 5 strokes and 16 deaths). Patients with SIRS more often had severe MR (79.5% vs. 62.7%, p=0.02) and adverse left ventricular (LV) remodeling indicated by lack of reduction in end-diastolic diameter (LVEDD) at follow-up (p=0.12 for SIRS-patients vs. p=0.0012 for non-SIRS patients). After adjustment for pertinent variables, SIRS (HR 3.24, CI 1.13-9.31, p=0.03) was independently associated with MACE. Conclusion: SIRS after M-TEER is a strong independent predictor of MACE. Closer follow-up is warranted as patients with SIRS have more severe MR and unfavorable LV remodeling at follow-up.

NCMP-29. BRAIN LESIONS IN A TEEN WITH NEWLY DIAGNOSED T-CELL ALL AND SARS-COV-2 INFECTION

Abstract T-cell Lymphoblastic Leukemia (T-cell ALL) accounts for up to 15% of all newly diagnosed cases of acute lymphoblastic leukemia in pediatric patients (0-18 years old). Patients are at risk of opportunistic infections during induction therapy with up to 2% developing blood stream infections when their absolute neutrophil count is above 1,500. We report a case of a 15-year-old female with High-Risk T-cell ALL, CNS1 (negative CNS disease), presenting with three days of headaches, photophobia, and non-neutropenic fever. She completed induction chemotherapy one week earlier with vincristine, daunorubicin, calaspargase and a 28-day course of dexamethasone. On physical exam, she had no focal deficits or changes in sensation or strength. CBC was notable for a white blood cell count: 7500, hemoglobin: 8.6, platelets: 328,000 and ANC (Absolute Neutrophil Count): 4700. The patient was also COVID positive on admission. A contrast enhanced MRI brain demonstrated multiple diffusion restricting and peripherally enhancing lesions, concerning for intracranial abscesses. Neurosurgery performed a burr hole craniotomy and aspirated 5 mL of purulent drainage, the culture of which grew Aspergillus fumigatus complex. The patient was started empirically on Voriconazole, in addition to broad spectrum antibiotic coverage pending culture results, due to excellent CNS penetration and proven superiority to amphotericin-based therapy for invasive aspergillosis. Micafungin was added due to CT chest demonstrating nodular infiltrates, suggesting primary pulmonary aspergillosis with CNS dissemination. The patient improved symptomatically without further sequelae. Patients with COVID-19 on prolonged courses of corticosteroids are at higher risk of developing fungal co-infections regardless of neutrophil count. While pulmonary aspergillosis is the most common location of a COVID-19 aspergillus coinfection, there have been documented reports of intracranial micro-abscesses. Contrast-enhanced brain MRI should be obtained in any patient with a recent history of COVID-19 presenting with new neurological symptoms, especially in a patient with a recent history of corticosteroids.

Association of Systemic Inflammatory Response Syndrome With Cardiovascular Events After Mitral Transcatheter Edge-to-Edge Repair.

Systemic inflammatory response syndrome (SIRS) following cardiovascular interventions is associated with adverse events during hospitalization and follow-up. Mitral transcatheter edge-to-edge repair is increasingly utilized for treatment of mitral regurgitation (MR). We investigated whether SIRS following mitral transcatheter edge-to-edge repair may occur and be associated with adverse clinical outcomes. A total of 158 consecutive patients with severe MR undergoing mitral transcatheter edge-to-edge repair were studied. SIRS was defined by leukocytosis (≥12 × 109/L) and fever (≥38 °C) within 48 hours after intervention. Baseline inflammation was measured by absolute neutrophil and lymphocyte counts and neutrophil-lymphocyte ratio. The primary end point of major cardiovascular events was the composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. Recurrent MR at follow-up was also recorded. The mean patient age was 80.8±8.8 years. Forty-four (27.9%) developed SIRS. Neutrophil-lymphocyte ratio correlated with onset of leukocytosis and fever (P=0.04). During a median follow-up of 12.5 (5.4-17.4) months, the primary end point occurred in 27 (17.1%) patients (6 myocardial infarction, 5 strokes, and 16 deaths). Patients with SIRS more often had severe MR (79.5% versus 62.7%, P=0.02) at follow-up. After adjustment for pertinent variables, SIRS (HR 2.73 [95% CI, 1.08-6.86]; P=0.03) was independently associated with major cardiovascular events. SIRS after mitral transcatheter edge-to-edge repair is a strong independent predictor of major cardiovascular events. Closer follow-up is warranted because patients with SIRS have more severe MR at follow-up.

Association between Hematological Parameters and Severity of COVID-19 disease

Background This study aimed to determine the relationships between hematological parameters- hemoglobin, Total Leucocyte Counts (TLC), platelet counts, Absolute Neutrophil Counts (ANC), Absolute Lymphocyte Counts (ALC), Neutrophil Lymphocyte Ratio (NLR), Systemic Immune Inflammatory Index (SII), Neutrophil Monocyte Ratio (NMR), Platelet Lymphocyte Ratio (PLR) and the severity of COVID-19 disease and their use in predicting severity of COVID-19 disease. Methods and Material This was a prospective, observational, single-center study of 573 symptomatic adult inpatients of COVID 19 admitted to our tertiary care center. Statistical analysis used The above-mentioned hematological parameter levels were noted and compared between the two categories of COVID-19 disease, namely non-severe and severe COVID-19 using logistic regression methods. Their cut-off values were detected using the ROC curve. Results The median TLC, ANC, NLR, SII, NMR, PLR were notably higher in patients with severe COVID-19 than in those with non-severe COVID-19. Logistic regression analysis showed that NMR (OR=1.029, p=0.006) and ALC (OR=0.999, p=0.002) were statistically significant independent predictors of COVID-19 severity. Conclusions The hematological parameters mentioned, can be used for predicting severe COVID-19 disease at admission. ALC and NMR levels could be used as hematological markers to predict severity of COVID-19 in adult patients with their cut off values being &lt; 1105 cells/cubic millimeter and &gt; 10.434 respectively.

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.

A Rare Case of Warm Autoimmune Hemolytic Anemia and Massive Splenomegaly in Uncontrolled Grave's Disease

Background: Autoimmune hemolytic anemia (AIHA) occurs when a person's immune system produces autoantibodies that attack their red blood cells, leading to their destruction. Warm AIHA, the most common form of AIHA, is caused by antibodies such as IgG that are active at body temperature. Warm AIHA can be primary or associated with underlying conditions like autoimmune disorders, lymphoproliferative disorders, immunodeficiencies, and infections, due to some form of immune system disruption. Clinical signs include anemia, jaundice, and mild to moderate splenomegaly. Case Presentation: A 36-year-old man with a history of Graves' disease (GD) (on methimazole) presented with jaundice. Despite being on methimazole, his thyroid levels were uncontrolled due to medication non-adherence, so his outpatient methimazole dose had been increased to 40 mg. Initial labs were notable for the following: a white blood cell count of 1.5 k/mm3, hemoglobin (Hgb) of 5.0 g/dL, platelet count of 78 k/mm3, total bilirubin of 13.1 mg/dL, reticulocyte percentage of 13.1%, lactate dehydrogenase (LDH) of 304 U/L, undetectable haptoglobin, absolute neutrophil count (ANC) of 0.95 k/mm3, thyroid stimulating hormone &amp;lt;0.01 mIU/L and a free T4 of 3.77 ng/dL. CT scan of the abdomen pelvis with contrast showed splenomegaly measuring 24.4 cm. Some reticulocytes were noted on the peripheral smear. The patient was diagnosed with AIHA, with warm antibodies noted on the Coombs test. In terms of workup for the etiology of his AIHA, the following infectious workup was negative: blood parasite smear, HIV, and Lyme enzyme immunoassay. Bone marrow (BM) biopsy flow cytometry showed no immunophenotypic evidence of acute leukemia, non-Hodgkin lymphoma, or high-grade myelodysplasia. He was aggressively transfused with 5 units of PRBCs and started on 1 mg/kg of prednisone daily. He was started on filgrastim 300 mcg 2 times a week for his leukopenia. Post these treatments his hemolysis labs improved to Hgb of 10.4 g/dL, reticulocyte percentage of 4.02%, total bilirubin of 3.1mg/dL, LDH of 141 U/L and haptoglobin of 78 mg/dL. His methimazole was held inpatient due to low ANC count. A trial of lithium was started for GD which led to limited improvement. The patient was discharged on daily prednisone and planned weekly rituximab infusions for AIHA. The patient was discharged without an anti-thyroid agent, with plans for close follow-up outpatient for thyroidectomy vs radioiodine ablation. Conclusion: The patient's severe Warm AIHA appeared acute, however the massive splenomegaly indicated a chronic low-level hemolytic process. Because the patient did not have any diagnostic findings consistent with hematologic malignancy or infection, and given the context of his recent history, it is reasonable to suspect that this presentation can be attributed to uncontrolled GD. Although the exact pathophysiology of the association is still unclear, the autoimmune nature of GD and hyperthyroidism are thought to contribute to the hemolysis. Warm AIHA is the rarest hematologic manifestation of GD, and literature on the topic has been limited to single case reports. Our case is also unique in that the Warm AIHA was seen in a patient with established GD, and not as an initial presentation of the disorder. To our knowledge, this is also the first case of Warm AIHA with this severe degree of splenomegaly, which can only be explained by the chronic nature of the patient's GD. The response to treatment for AIHA suggests an autoimmune nature of the condition, but the underlying GD did not respond to medical therapy. Overall, this case adds to the literature, as a unique hematologic presentation of an uncontrolled autoimmune disorder.

Monocytosis Is an Independent Risk Factor for Survival in Essential Thrombocythemia - a Revised Triple-a Prognostic Score (AAA+A) Based on Age and Absolute Monocyte, Neutrophil, and Lymphocyte Counts

Monocytosis Is an Independent Risk Factor for Survival in Essential Thrombocythemia - a Revised Triple-a Prognostic Score (AAA+A) Based on Age and Absolute Monocyte, Neutrophil, and Lymphocyte Counts