Absolute Neutrophil Count Research Articles

Risk factors associated with sepsis in children with acute lymphoblastic leukemia and febrile neutropenia

Background Children with acute lymphoblastic leukemia (ALL), especially those with febrile neutropenia, are susceptible to sepsis. Several factors have been associated with the occurrence of sepsis in children with leukemia. Objective To identify potential risk factors associated with sepsis in children with ALL and febrile neutropenia. Methods This cross-sectional study was done in children with ALL who sought treatment at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from January 2019 to March 2022. We recorded patients’ gender, age, nutritional status, absolute neutrophil count (ANC), co-infection, prophylactic antibiotic use, and phase of chemotherapy. Results Of 131 subjects, 57.3% were male and 42.8% were wasted. Subjects had a median age of six years old and median ANC of 230 cells/mm3. Furthermore, 48.9% of subjects had co-infections, 87.8% had not received prophylactic antibiotics, and 48.9% were in the induction phase of chemotherapy. Multiple logistic regression analysis revealed that older age [OR 1.16 (95%CI 1.04 to 1.29); ?=0.149; P=0.008] and co-infection [OR 12.9 (95%CI 5.01 to 33.21); ?=2.551; P<0.001] were significantly associated with sepsis in children with ALL and febrile neutropenia. Bronchopneumonia was the most common co-infection (72.5%). Conclusion Older age and co-infection are significantly associated with sepsis in children with ALL and febrile neutropenia.

Neutrophil-Lymphocyte Ratio Values in Schizophrenia: A Comparison between Oral and Long-Acting Antipsychotic Therapies.

Schizophrenia is a mental disorder affecting approximately 0.32% of the global population, according to the World Health Organization. Antipsychotic medications are used to treat this condition by inhibiting D2 dopamine and 5HT2 serotonin receptors. The selection of the appropriate mode of delivery for these drugs is based on factors such as patient adherence, clinical presentation, and patient preferences. However, additional drivers of treatment selection are required in clinical practice. Mounting evidence suggests that neuroinflammation plays a crucial role in the pathogenesis of schizophrenia. NLR, a cost-effective biomarker of inflammation, has increased in several psychiatric conditions and may represent a valid method for studying the inflammatory stage in schizophrenia, relapse, and the first episode of psychosis. The aim of this study is to evaluate whether there are any variations in NLR values between patients given oral antipsychotics and those given long-acting antipsychotics. The study included 50 individuals with schizophrenia, either acute or in the follow-up phase. NLR was obtained by calculating the ratio of absolute neutrophil count (cells/μL) and absolute lymphocyte count (cells/μL). Patients on long-acting antipsychotics exhibited significantly lower mean NLR scores (1.5 ± 0.7) compared to those on oral antipsychotics (2.2 ± 1.3) (p < 0.05). NLR appears promising as a neuroinflammatory biomarker. This study reveals significantly lower NLR values in patients on long-acting antipsychotics, which may signify reduced systemic inflammation and improved adherence.

Is It Possible to Use Inflammatory Markers as Potential Biomarkers for Chronic Urticaria?

Background: This study aimed to determine whether the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) at admission affect the transition of pediatric patients diagnosed with acute spontaneous urticaria to chronic urticaria. Methods: This study included 390 patients who presented to the Department of Pediatrics at Akdeniz University Hospital with acute spontaneous urticaria between January 2020 and December 2022. A statistical comparison was made between the hematological parameters of patients who developed chronic urticaria and those who did not. Neutrophil, lymphocyte, and platelet counts, as well as NLR, PLR, and SII ratios, were used for the comparison. Results: It was observed that acute urticaria progressed to chronic urticaria in 5.8% (n = 23) of the patients. No significant differences in lymphocyte, hemoglobin, and platelet counts were observed between the group progressing to chronic urticaria and the control group (P > 0.05). However, the chronic urticaria group had higher leukocyte and absolute neutrophil counts (P = 0.009 and P < 0.001, respectively). In addition, the NLR was significantly higher in the chronic urticaria group (P = 0.029), whereas no statistically significant difference was observed in the PLR (P = 0.180). The chronic urticaria group had a significantly higher SII than the control group (P = 0.011). Conclusion: Hematological parameters, particularly NLR and SII, may be useful indicators of the transition from acute to chronic urticaria in pediatric patients. The early identification of these markers could help monitor patients and guide treatment decisions. Further comprehensive studies are required to validate these findings.

High peripheral neutrophil and monocyte count distinguishes renal cell carcinoma from renal angiomyolipoma and predicts poor prognosis of renal cell carcinoma

BackgroundThe presence of peripheral inflammatory cells has been linked to the prognosis of cancer. This study aims to investigate the distinct roles of absolute neutrophil count (ANC) and absolute monocyte count (AMC) in differentiating renal cell carcinoma (RCC) from renal angiomyolipoma (RAML), as well as their prognostic significance in RCC. MethodsWe conducted a comprehensive analysis of peripheral immune cell data, clinicopathological data, and tumor characteristics in patients diagnosed with RCC or RAML from January 2015 to December 2021. Receiver operating characteristic (ROC) curves, as well as univariate and multivariate analyses, were employed to assess the diagnostic utility of AMC and ANC in differentiating between RCC and RAML. Kaplan-Meier curve analysis was used to study the survival of RCC patients with different AMC and ANC. The prognostic value of AMC and ANC in RCC was investigated using COX univariate and multivariate analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used for bioinformatic correlation analysis. ResultsA total of 1120 eligible patients were included in the study. The mean preoperative AMC and ANC in patients with RCC were found to be significantly higher compared to those in patients with RAML (P = 0.001 and P < 0.001, respectively). High preoperative AMC and ANC significantly correlated with smoking history, tumor length, gross hematuria, and high T Stage, N stage, and pathological grade. In multivariate analyses, an ANC> 3.205 *10^9/L was identified to be independently associated with the presence of RCC (HR = 1.618, P = 0.008). High AMC and ANC were significantly associated with reduced OS and PFS (P < 0.05), and ANC may be an independent prognostic factor. Public database analysis showed that signature genes of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) were highly expressed in ccRCC. ConclusionsElevated preoperative ANC and AMC can distinguish RCC from RAML and predict poor prognosis in patients with RCC. Furthermore, the signature genes of TAMs and TANs exhibit high expression levels in clear cell RCC.

Association of absolute neutrophil count with outcomes in patients with head and neck cancer treated with chemoradiation.

e18055 Background: Systematic inflammation plays an integral role in tumor development and metastasis. High neutrophil counts, among various peripheral blood biomarkers, have been shown to be associated with worse survival outcomes in multiple cancer types. To evaluate the absolute neutrophil count (ANC) as a prognostic biomarker in head and neck cancer, we performed an observational cohort study of patients undergoing definitive chemoradiation. Methods: Our institutional database at the Roswell Park Comprehensive Cancer Center was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation between June 2007 and April 2023. ANC was analyzed as a continuous variable. Survival outcomes were assessed using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Fine-Gray MVA was used to analyze failure outcomes with death as a competing event. To reduce selection bias, propensity score matching was performed using ANC as a dichotomous variable with its median value as a cutoff. Subgroup analyses were performed among p16-negative and p16-positive cohorts. Results: A total of 668 patients who met our criteria. Median follow up was 30.3 months (interquartile range 9.9-60.7). Elevated ANC as a continuous variable was associated with worse overall survival (OS; adjusted hazards ratio [aHR] 1.02, 95% confidence interval [CI] 1.01-1.04, p=0.003), progression free survival (PFS; aHR 1.03, 95% CI 1.01-1.04, p&lt;0.001), and distant failure (DF; aHR 1.03, 95% CI 1.01-1.05, p=0.007), but not locoregional failure (LRF; aHR 1.02, 95% CI 1.00-1.05, p=0.10). Similar findings were noted among 278 matched pairs (OS: hazards ratio [HR] 1.66, 95% CI 1.23-2.26, p=0.001; PFS: HR 1.74, 95% CI 1.31-2.29, p&lt;0.001; LRF: HR 1.66, 95% CI 0.98-2.80, p=0.06; DF: HR 1.64, 95% CI 1.03-2.60, p=0.04). On subgroup analysis, among 118 patients with p16-negative tumors, elevated ANC as a continuous variable was not associated with OS (aHR 1.00, 95% CI 0.90-1.11, p=0.97) and PFS (aHR 0.97, 95% CI 0.87-1.08, p=0.54). The number of LRF (n=21) and DF (n=17) were too few to analyze in this subgroup. However, among 344 patients with p16-positive tumors, high ANC was associated with worse OS (aHR 1.03, 95% CI 1.00-1.06, p=0.046), PFS (aHR 1.05, 95% CI 1.02-1.07, p&lt;0.001), LRF (aHR 1.08, 95% CI 1.05-1.12, p&lt;0.001), and DF (aHR 1.04, 95% CI 1.01-1.08, p=0.02). Conclusions: Our study suggested that elevated ANC was an independent, adverse prognostic factor for worse survival and distant metastasis outcomes. Similar findings were also observed among patients with p16-positive tumors, with high ANC also associated with worse locoregional failure. Further studies are warranted to tailor interventions based on such biomarkers.

Clonal Hematopoiesis is Associated With Severe Cytokine Release Syndrome in Patients Treated With Chimeric Antigen Receptor T-Cell (CART) Therapy

Among patients receiving CD19 or B-cell maturation antigen (BCMA) CAR T therapy, inflammation pre- and post-CAR T infusion is implicated in the development of toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and likely contributes to prolonged cytopenias. Clonal hematopoiesis (CH), the clonal expansion of hematopoietic stem cells harboring somatic mutations, has been associated with inflammasome upregulation. Herein, we examined the prevalence of pre-CAR T CH in a predominantly transplant-naïve cohort of recipients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), and assessed the relationship between the presence of CH mutations and CAR T-related outcomes including CRS, ICANS, prolonged cytopenia, progression-free survival (PFS), and overall survival (OS). This study included 62 patients with NHL or MM who underwent CD19 or BCMA CAR T therapy from 2017 to 2022 at City of Hope and had available pre-CAR T cryopreserved peripheral blood mononuclear cells (PBMCs). DNA was isolated with QIAamp DNA Mini Kit (Qiagen) from PBMC samples (94% collected <30d of CART infusion), on which we performed targeted exome sequencing (108 pre-defined gene panel with 1000x sequencing depth) to determine the presence of CH (variant allele frequency [VAF] ≥2%). Multivariable logistic regression was used to examine the association between CH and absolute neutrophil count (ANC) recovery at day +30 and +60, maximum grade CRS and ICANS, grade <2 versus 2+, and OS and PFS at 1y. Covariates considered were age at CART, baseline ANC, sex, race, CAR-HEMATOTOX, LDH, bridging therapy (Y/N), and number of prior lines of therapy. Fifteen (24%) patients had at least one pathogenic CH mutation; 2 (13%) had ≥2 CH mutations concurrently. DMT3A mutations were the most common; 29% of mutations had VAFs >10%. Patients with CH were significantly more likely to develop grade ≥2 CRS (60% versus 28%, p = .03) compared to those without CH (odds ratio [OR] 3.9, 95% CI 1.2-13.2; p = .027). Accounting for baseline ANC (which was higher among the CH cohort and associated with delayed ANC recovery, p = .02) patients with CH did not have a significantly different rate of delayed ANC recovery compared to those without CH (adjusted OR 0.37, 95% CI 0.09-1.5; p = .17). There was no association between CH and ICANS, nor with 1y PFS or OS. CH was frequent (24%) in this cohort of CAR T recipients and was associated with a higher risk of development of grade ≥2 CRS after CAR T. Additional validation studies are currently underway, which may set the stage for consideration of pre-CAR T CH as a biomarker for risk stratification towards more proactive CRS prophylaxis. Translational studies could aim to prove a direct relationship between CH-mutated myeloid cells and CRS.

Guard 01: A randomized, multicentre, controlled trail on the prophylactic use of efbemalenograstim alfa for concurrent chemo-radiotherapy induced neutropenia.

TPS12155 Background: Concurrent chemo-radiotherapy plays a crucial role in the treatment of various advanced-stage malignant tumors. However, it is often associated with significant hematologic toxicity, especially leukopenia and neutropenia, which may lead to treatment interruptions, reduced efficacy, and even severe infections. Efbemalenograstim alfa is a novel long-acting recombinant human granulocyte colony stimulating factor (rhG-CSF) combined of an immunoglobulin (Ig) G2-Fc fragment and two rhG-CSF molecules. Although efbemalenograstim alfa has been confirmed to be effective in the prevention of chemotherapy induced neutropenia by a number of clinical studies, its prophylactic efficacy during concurrent chemo-radiotherapy was seldom investigated. Guard-01 is aimed to evaluate the effectiveness and safety of primary preventive use of efbemalenograstim alfa in concurrent chemo-radiotherapy. Methods: This study is a multicenter, open-label, randomized, controlled clinical trial involving 120 patients who are planned to receive definitive concurrent chemo-radiotherapy with non-small cell lung cancer, small cell lung cancer, esophageal cancer, nasopharyngeal carcinoma, head and neck squamous cell carcinoma, or cervical cancer. Patients will be randomized into efbemalenograstim alfa arm or control arm in a 1:1 ratio on the first day of the first concurrent chemo-radiotherapy cycle. The stratification factor is chemotherapy regimen of the patients. Approximately 48 (±4) hours after the completion of each chemotherapy cycle, patients in the efbemalenograstim alfa arm will receive efbemalenograstim alfa (20 mg per dose, subcutaneous injection) for prevention. Patients in the control arm will receive rhG-CSF (5 μg/kg/day) when the absolute neutrophil count (ANC) is less than 1.0×109/L, and treatment will be discontinued when ANC reaches ≥5×109/L. The primary endpoint is the incidence of grade ≥3 neutropenia (ANC&lt;1.0×109/L) during concurrent chemo-radiotherapy. The trial is opened in November 2023 and will be conducted in 8 hospitals with the aim of recruiting 120 evaluable patients (4 patients are recruited untilled 29-Jan-2024). Clinical trial information: ChiCTR2300077504.

Prognostic factors for survival in NSCLC treated with immunotherapy: An institutional analysis.

e20591 Background: Immune check point inhibitors (ICIs) are the cornerstone of treatment for patients with advanced NSCLC. However, not all patients benefit from ICIs and some develop significant immune-mediated toxicities. There is limited data regarding prognostic factors in NSCLC patients treated with ICIs. Imaging features can complement clinical variables in predicting response to ICIs. This study aims to evaluate CEA, blood leukocyte markers, and novel CT-derived radiomic features as factors predictive of survival in this patient population. Methods: In this retrospective study, clinical data from patients with advanced stage NSCLC treated with ICIs at Stony Brook University Hospital from 2016 to 2021 were collected. Baseline and subsequent CEA (carcinoembryonic antigen), ANC (absolute neutrophil count), ALC (absolute lymphocyte count), NLR (neutrophil to lymphocyte ratio), AEC (absolute eosinophil count), and AMC (absolute monocyte count) were evaluated as independent prognostic factors. 3-D segmentation of ipsilateral lung lobe was obtained using U-Net and radiologist report of tumor location. 600 stable IBSI-standardized features were extracted from the region using PyRadiomics. The discriminative ability of clinical and image-derived variables was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Results: This study included 80 patients. Objective response rate (ORR) was 25.0% with 1-year OS of 58.0%. PD-L1 expression ≥ 50% was significantly associated with survival (p &lt; 0.02). Decrease in CEA (p &lt; 0.01) and 5% increase in AEC (p = 0.027) significantly correlated with survival. Age, sex, clinical stage, ANC, ALC, NLR, AMC did not significantly predict survival. Three image biomarkers that correlated with median enhancement of tissue on chest CT, and degree of tissue heterogeneity were significant predictors of mortality (p &lt; 0.02). A multivariable model with clinical inputs outperformed one with radiomic features only (C-index 0.70 vs. 0.64). Clinical and radiomic inputs together performed well in predicting survival (C-index 0.76). Conclusions: Changes in CEA and AEC were the strongest predictors of survival in advanced NSCLC patients treated with ICIs. This study suggests that combined clinical and radiomic biomarkers (quantifying local lobar heterogeneity) can identify patients most likely to benefit from immunotherapy. [Table: see text]

White blood cell kinetics in patients with gynecologic cancer receiving mecapegfilgrastim prophylaxis: A multicenter real-world study.

e17502 Background: Some studies have indicated that using granulocyte-colony stimulating factor (G-CSF) following chemotherapy in patients with solid tumors may increase the risk of excessive white blood cell (WBC) elevation. In this real-world study, we aimed to assess the changes in WBC counts after prophylactic administration of 6 mg mecapegfilgrastim (a long-acting G-CSF) in multiple chemotherapy cycles among Chinese gynecological cancer patients, with a particular focus on those with low body weight (≤50 kg). Methods: A multicenter prospective cohort study was conducted involving gynecological cancer patients who received at least two consecutive chemotherapy cycles with mecapegfilgrastim 6 mg (administered 24 hours post-chemotherapy) between October 2019 and November 2021. Absolute WBC and absolute neutrophil counts (ANC) were recorded at baseline and on the 7th and 14th days of each cycle. Results: A total of 256 gynecological cancer patients completing 2-4 treatment cycles, including 86 with cervical cancer, 136 with ovarian cancer, and 34 with endometrial cancer, were analyzed. Of them, 58 had a pre-chemotherapy body weight of ≤50 kg, and 198 had a body weight of &gt;50 kg. The majority of patients received taxane-based chemotherapy regimens with a cycle duration of ≥14 days. For day 7 post-chemotherapy WBC counts, data were collected from 535 cycles, including 125 cycles in the ≤50 kg group and 410 cycles in the &gt;50 kg group. Elevated WBC counts (&gt;10.0×10^9/L) were observed in 56 cycles (44.8%) in the ≤50 kg group and 177 cycles (43.2%) in the &gt;50 kg group. On day 14 post-chemotherapy, data from 505 cycles, comprising 115 cycles in the ≤50 kg group and 390 cycles in the &gt;50 kg group, indicated elevated WBC counts in 27 cycles (23.5%) in the ≤50 kg group and 63 cycles (16.2%) in the &gt;50 kg group. In the ≤50 kg group, 3 cases (5.2%) experienced an ANC &lt;0.5×10^9 /L, with no febrile neutropenia observed. In the &gt;50 kg group, 11 cases (5.6%) experienced an ANC &lt;0.5×10^9 /L, with 1 patient (0.51%) experiencing febrile neutropenia. Conclusions: In patients with low body weight (≤50 kg), the administration of 6 mg mecapegfilgrastim effectively stabilizes WBC elevation, exhibiting a favorable safety and efficacy profile. This regimen ensures the timely and appropriate progression of patients to subsequent cycles of chemotherapy. WBC counts in patients. [Table: see text]

Development and Validation of an In-Hospital Mortality Prediction Model for Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) often face unknown risks during acute exacerbation of the disease (AECOPD), which could potentially result in mortality. This study aimed to develop and validate a nomogram model for predicting the risk of in-hospital mortality in AECOPD patients. Clinical data of patients hospitalized at The Second People's Hospital of Wuhu City for AECOPD between January 2013 and December 2022 were retrospectively collected. Variables underwent selection through LASSO regression and multivariable logistic regression to develop a nomogram model. The model's predictive performance was assessed using the concordance index, calibration curve, and decision curve analysis (DCA), with internal validation conducted using the bootstrap method. A total of 1224 patients were included in this study, with 98 (8%) deaths occurring during hospitalization. LASSO regression identified 11 variables, used to construct model A. Further multivariable logistic regression was conducted to select variables with P < 0.05 to establish model B. model B was selected as the final model based on discrimination, calibration, and clinical utility, encompassing variables including acute respiratory failure, lung cancer, heart rate, hemoglobin, absolute neutrophil count, serum albumin, blood urea nitrogen, and serum chloride. The nomogram model achieved a concordance index of 0.858. Internal validation of the model was conducted using the bootstrap method with 500 repetitions, resulting in a concordance index of 0.851 (95% CI: 0.805, 0.893). The calibration curve demonstrated a good fit, with a Hosmer-Lemeshow goodness-of-fit test P-value of 0.520. Moreover, DCA findings suggested patient benefit within a threshold probability range of 0.02 to 0.73, with a maximum net benefit of 0.07. The model constructed in this study has good predictive performance, which helps clinical doctors identify patients at high risk of death early.

N9: Pilot study of novel shortened induction for high-risk neuroblastoma.

10052 Background: N9 induction for high-risk neuroblastoma was designed to limit non-hematological toxicity (especially ototoxicity) and to prevent relapse in the central nervous system (CNS). N9 builds on 2 novel regimens: high-dose cyclophosphamide-topotecan-vincristine (CTV) and ifosfamide-carboplatin-etoposide (ICE), each with good penetration across the blood-brain barrier. Methods: N9 is a pilot study (Clinicaltrials.gov.NCT04947501) to assess feasibility and safety. Secondary/exploratory objectives include response, collection of peripheral blood stem cells (PBSCs; ≥5x106/kg CD34(+) cells sufficient for ≥2 rescues), tumor resection, and assessment of central nervous system relapse. Early stopping rules centered on excessive delay in timing of chemotherapy. Eligibility criteria included age &gt;1-to-&lt;13 years; 1 prior chemotherapy cycle was allowed. CTCAE Version 5.0 and International Neuroblastoma Response Criteria are used.N9 comprises 4 cycles of chemotherapy. Cycles start after absolute neutrophil count is &gt;500/μL, platelets &gt;100,000/μL, and non-hematologic toxicities grade ≤2. Intervals of 21-28 days between start of cycles are foreseen. PBSC collection and surgery follow &gt;3 cycles. Cycles #1 and #4 (CTV): cyclophosphamide 70mg/kg/day, days 1-2, topotecan 2mg/m2/day, days 1-4, and vincristine 0.067mg/kg, day 1. Cycle #2 (ICE): ifosfamide 1500mg/m2/day, days 1-5, carboplatin 400mg/m2/day, days 1-2, and etoposide 100mg/m2/day, days 1-5. Cycle #3: cyclophosphamide (as in CTV) and 72-hr infusions of doxorubicin 75mg/m2 and vincristine 0.067mg/kg. Results: The target number of 15 patients were enrolled: 10/2021-9/2023; age 1.5–9.8 (median 3.3) years; 14 stage M, 1 stage L2; and 10 post-1 cycle of other chemotherapy. They completed N9 without undue toxicity: all cycles started on time, organ functions remained intact, 11/11 patients tested had no ototoxicity, and acute toxicities were typical for myelosuppression (including uncomplicated fever/neutropenia). Responses were complete (n=6), partial (n=5), and stable disease (n=4). The target number of PBSCs was collected in 12 patients (9-75, median 14 x106/kg CD34(+) cells), 4x106/kg in 2 patients, and pending in 1. All patients had gross total resections of the primary tumor. Post-N9, patients did not undergo transplant, but proceeded to immunotherapy (naxitamab) or chemoimmunotherapy (naxitamab+irinotecan-temozolomide). Of 9 with residual disease post-N9, 7 achieved CR (median of 5.6 months from study entry) and 1 achieved metabolic CR (16 months), though 3 subsequently relapsed (no CNS). Conclusions: N9 shows promise for reducing chemotherapy and long-term toxicity. Less chemotherapy without compromising survival is a realistic goal by virtue of the advances with anti-GD2 monoclonal antibodies which, in combination with GM-CSF+low-dose chemotherapy, are highly effective against chemo-resistant disease in bone/bone marrow. Clinical trial information: NCT04947501 .

The development of a prediction model based on random survival forest for the prognosis of non- Hodgkin lymphoma: A prospective cohort study in China

Background and objectiveThe pathological staging of non-Hodgkin lymphoma (NHL) is complex, the clinical manifestations are varied, and the prognosis differ considerably. To provide a useful reference for early detection and effective treatment of NHL, we developed a random survival forest (RSF) prognostic model based on machine learning (ML) algorithms using prospective cohort data collected from Chongqing Cancer Hospital from Jan 1, 2017 to Dec 31, 2019 (n = 1449) to compare with the traditional cornerstone method Cox proportional hazards (CPH) model and evaluate the predictability of the model. MethodsPatients were randomly split into a training cohort (TC) and validation cohort (VC) based on 65/35 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extracted the important features. And the RSF was modeled to explore the prognostic factors impacting the overall survival (OS) of patients with NHLs in the TC and validated in the VC. The C-index, the Integrated Brier Score (IBS), Kaplan-Meir method, the receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) were selected to measure performances and discriminations of the models. In addition, individual survival probability predicted for NHL patients. ResultsAccording to the features extracted by LASSO model and univariable Cox model, 16 variables were selected to develop the RSF model with log-rank splitting rule, which were age, ethnicity, medical insurance, Ann Arbor stage, pathology, targeted-therapy, chemo-therapy, peripheral blood neutrophil count to lymphocyte count ratio (NLR), peripheral blood platelet count to lymphocyte count ratio (PLR), serum lactate dehydrogenase (LDH), CD4/CD8, platelet (PLT), absolute neutrophil count (ANC), lymphocyte (LYM), B-symptoms, and (CPR) were important prognostic factors. Compared to the CPH model (C-index = 0.748, IBS = 0.166), the RSF model (C-index = 0.786, IBS = 0.165) is outperformed in predictability and accuracy. The AUC of the RSF model to estimate the 1-, 3-, and 5-year OS in TC were 0.847, 0.847, and 0.809, respectively; while those in the CPH were 0.816, 0.803, and 0.750, respectively. ConclusionsTo provide practical implications for the implementation of individualized therapy, the study constructed a high-performed RSF model and reveal that it outperformed the traditional model CPH. And the RSF model ranked the risk variables. In addition, we stratified the risk of NHL patients and estimated individual survival probability based on the RSF model.

Factors before leukapheresis that correlate with severe cytopenia and therapy related myeloid neoplasm post CAR-T.

7038 Background: While chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment for hematological malignancies, severe (≥ grade 3,Gr 3, CTCAE) cytopenias post CAR-T and therapy related myeloid neoplasms (t-MN) are particularly difficult to manage. Survival after diagnosis of t-MN is dismal. Management of ≥Gr 3 cytopenias that do not recover by month 3 after CAR-T require frequent monitoring and transfusion support. Growth factor and thrombopoietin mimetics have variable success, with stem cell boost emerging as having more consistent success. Evaluation for CAR-T eligibility, prior to leukapheresis, is the critical timepoint where factors identified at this time could inform risks and benefits of CAR-T versus alternative treatment and for consideration of stem cell collection in patients who may benefit from stem cell boost to treat severe cytopenia post CAR-T. Methods: We conducted a retrospective analysis comparing clinical data of patients (pts) with lymphoma (NHL) and multiple myeloma (MM) treated with FDA-approved and investigational CAR-T between 01/2016 – 06/2022 at Mayo Clinic. Prolonged cytopenias were defined as hemoglobin (Hg)&lt;8 g/dL, absolute neutrophil count (ANC)&lt;0.5 x 109/L, and/or platelet count (PLT)&lt;50 x 109/L at 3 months after CAR-T. Pts with progressive disease were excluded from cytopenia analysis. Logistic regression to identify factors correlated with cytopenia and t-MN. Results: Among the 186 pts who received CAR-T, 42 (22%) patients developed severe cytopenia (26/102, 25%, in NHL; 16/84, 19% in MM); 15/186 (8%) had more than 1 concurrent cytopenia. Univariate analysis identified that baseline ferritin and CAR-HEMATOTOX score correlated with cytopenia. Multivariate analysis showed that advanced age (≥ 65 years) (HR 2.69, 95%CI 1.17 – 6.40, P = 0.02) and thrombocytopenia (HR 4.01, 95%CI 1.77 – 9.34, P = 0.001) were associated with severe cytopenia. Twenty (10.7%) patients [8 (40%) males] developed t-MN at a median of 9.5 months (IQR 4.8 – 19.3 months) after CAR-T (14/102, 13% in NHL; 6/84, 7% in MM). Univariate analysis identified ferritin and CAR-HEMATOTOX score correlated with t-NM. Multivariate logistic regression showed advanced age (HR 5.03; 95%CI 1.59-18.7, P= 0.009), hemoglobin ≤ 10 g/dl (HR 3.63, 95%CI 1.04-13.30, P = 0.04), and thrombocytopenia (HR 4.06, 95%CI 1.32-14.2, P 0.02) are significantly associated with development of post-CART t-MN. Conclusions: Advanced age, anemia and thrombocytopenia at the time of evaluation for CAR-T eligibility, prior to leukapheresis, are associated with the development of post-treatment severe cytopenia and t-MN. Larger, multi-center studies are needed to validate these findings.

The predictive value of the MASCC score in patients with febrile neutropenia.

e23059 Background: Febrile neutropenia (FN) is a life-threatening complication in patients receiving cytotoxic chemotherapy. Guidelines classify FN as a one-time oral temperature of greater than 38.3°C or sustained temperature greater than 38°C for ≥ 1 hour with an absolute neutrophil count (ANC) of less than 500 cells/μL or an ANC expected to decrease to less than 500 cells/μL within a 48-hour period. This condition has a high rate of hospitalization and mortality. Currently, the Multinational Association of Supportive Care in Cancer (MASCC) risk score is used to classify patients as high or low risk. The current study outlines the predictive role of MASCC scoring in risk stratifying patients with FN at our institution. Methods: This is a single-center, retrospective observational study. IRB approval was obtained for this study. Electronic medical record data was reviewed to record mortality, length of stay (LOS), and antimicrobial use as primary outcomes with age at time of admission, sex, race, type of malignancy, any confirmed infection diagnosis, MASCC risk score, and subspecialist consultation as predictors of outcomes. Results: 220 records of possible FN episodes were screened, 160 were excluded leaving a total of 60 patients for review. The median age was 72.5 with 28 males and 32 females. Overall mortality rate was 10%.33 patients (55%) did not have an identifiable source of infection. Among the 27 patients with confirmed infection, 7 were associated with COVID-19, 12 had gram negative rod (GNR) sepsis and 8 were other bacterial infections. Patients with GNR sepsis had the highest mortality risk in which 4 of the 12 (33%) died. LOS was also significantly longer in patients with GNR sepsis. Lower MASCC scores were associated with identification of GNR sepsis. Of the patients with MASCC score of &lt; 24, significantly more patients 7/20 (35%) developed GNR sepsis compared to 5/40 (12.5%) of those with MASCC score of 24 or greater (p = .004). Patients with GNR sepsis received a mean 5.7 days of broad spectrum antibiotics compared to 3 days in those without, (p &lt; 0.001). Those with no identified infection had significantly lower LOS (4.5 days) compared to the groups with GNR sepsis (11.1 days) or other bacterial infections (10.1 days). Conclusions: Febrile neutropenia is a complication of cytotoxic chemotherapy that warrants special attention due to high mortality rates. We found lower MASCC scores were associated with GNR sepsis and that in the setting of FN these patients had higher mortality rates and longer LOS. This highlights the importance of risk stratification with MASCC index scoring as early recognition and treatment of high risk patients could lead to improved patient outcomes.

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) &lt;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 &gt;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.

Usefulness of extended inflammatory parameters related to neutrophil activation reported by Sysmex XN-1000 hematology analyzer for predicting complicated acute appendicitis. Comparison with canonical inflammatory laboratory tests

AimAccurate diagnosis of complicated appendicitis is of importance to ensure that patients receive early and effective treatment, minimizing the risk of postoperative complications to promote successful recovery. Biochemical markers are a promising tool to identify complicated appendicitis. We aimed to evaluate the potential role of novel parameters related with neutrophil activation, known as “Extended Inflammation Parameters” (EIP), included in blood cell count reported by Sysmex XN-Series analyzers, compared to other canonical biomarkers in identifying complicated appendicitis. MethodProspective observational study including patients with confirmed diagnosis of acute appendicitis. C-reactive protein (CRP), procalcitonin, cell blood count, including white blood cell (WBC), absolute neutrophil (ANC) and immature granulocyte (IG) count and EIP (neutrophil reactivity [NEUT-RI] and granularity intensity [NEUT-GI]) were analyzed before surgery. Their accuracy to diagnose complicated appendicitis was tested in an ROC curve analysis. ResultsOur population study included 119 patients, and appendicitis was complicated in 58 (48.7%). NLR, CRP and procalcitonin levels, ANC and IG count and NEUT-RI and NEUT-GI were higher in patients with complicated appendicitis. Regarding accuracy for complicated appendicitis, CRP was the biomarker with the highest performance (ROC AUC: 0.829), with an optimal cutoff of 73.1 mg/L (sensitivity: 63.8%, specificity: 88.5%). NEUT-RI and NEUT-GI achieved both significant but poor accuracy, with ROC AUC of 0.606 and 0.637, respectively. ConclusionsNovel laboratory tests reported by Sysmex XN-Series analyzers have poor accuracy for identifying complicated appendicitis. In this study, CRP was the biomarker with the highest performance and may be useful as predictor of the severity of acute appendicitis.

Development of a novel granulocyte scoring system for use as a predictive/prognostic biomarker in patients with advanced melanoma undergoing treatment with combination immunotherapy.

9551 Background: Despite the implementation of immune checkpoint inhibition (ICI) for patients with metastatic melanoma, there remains an unmet clinical need for predictive/prognostic biomarkers to determine, from outset, which patients will derive benefit. Recent literature has suggested a significant role for granulocyte subsets in the development of resistance to systemic therapies, with an associated role in adaptive immunity. Methods: We sought to establish a novel immunological scoring system to use as a predictive/prognostic biomarker in patients with advanced melanoma being treated with ICI. In this retrospective, single centre study evaluating patients with advanced melanoma treated with combination ipilimumab and nivolumab, progression free survival (PFS) and overall survival (OS) were compared between groups defined by neutrophil, lymphocyte, eosinophil, monocyte and basophil counts. Data from 226 patients was collected at baseline, week 3, week 6, first response scan and at progression. Baseline and week 3 data was the focus of this primary analysis. Kaplan-Meier estimation and Cox regression analysis were performed. Results: Univariate analysis demonstrated that absolute neutrophil, eosinophil and basophil count strongly associates with PFS and OS outcomes at week 3. Combination of these counts into a novel neutrophil to eosinophil + basophil ratio (NEBR, (N/(E+B)) was assessed as a scoring system. High NEBR was associated with poorer PFS and OS at baseline and week 3 with consistently superior predictive/prognostic value than the well-established neutrophil to lymphocyte ratio (NLR). After accounting for covariates including concurrent steroids, infection and LDH, high NEBR remained significantly associated with worse PFS at baseline and poorer PFS and OS at week 3. Conclusions: Our findings highlight NEBR as a novel immunotherapeutic predictive/prognostic biomarker with potential clinical utility that warrants further investigation in patients with advanced melanoma and across other tumour groups. Further validation will be required through independent external datasets. [Table: see text]

Systemic inflammatory markers in neoadjuvant pembrolizumab therapy for triple-negative breast cancer: Prognostic insights and nomogram construction.

e12649 Background: Systemic inflammatory markers derived from peripheral blood cells, such as the neutrophils and lymphocytes ratio (NLR), derived neutrophil lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), and lymphocyte–monocyte ratio (LMR), have shown promise as prognostic markers. Currently, neoadjuvant treatment (NACT) for early triple-negative breast cancer (eTNBC) involves the addition of an immune therapy, and little is known about the variation of these markers in this specific context. Methods: This study evaluated two groups who received NACT for eTNBC in a single third-level cancer center. The first received NACT with EC X4 and a weekly paclitaxel regimen, the second pembrolizumab and NACT. A total of 70 patients were included, 37 patients in the pembrolizumab group. NLR was defined as the absolute blood neutrophil count (N) divided by the absolute lymphocyte count (L), dNLR was defined as the N divided by the derived L (absolute leukocyte count — N), PLR was defined as the absolute platelet count divided by the L, LMR was defined as the L divided by the absolute monocyte count. Association between systemic inflammatory markers and pathological complete response (pCR) was analyzed using statistical tests. Inflammatory markers were evaluated at the time of diagnosis, at the time of chemotherapy regimen change, and 1 week before surgery. The χ2 test or Fisher’s exact test was used for correlation and Student’s t-test to compare different groups. Results: The pCR rates were 60,6% in the standard therapy and 77,8% in the pembrolizumab. There were no significant differences in clinical characteristics between the two groups. NLR, dNLR, PLR and LMR at 6 months showed significant differences compared to baseline levels. dNLR in the immunotherapy group, at the end of therapy, showed statistical significance with the Welch Two Sample t-test with p-value = 0.001. Variables were weighted with respect to the type of treatment and the outcome was assessed as pCR. On the basis of these data, a nomogram was constructed to predict the likelihood of achieving pCR in patients undergoing neoadjuvant pembrolizumab therapy. Conclusions: This study highlights the potential of systemic inflammatory markers as prognostic indicators in patients with eTNBC undergoing NACT. dNLR is a novel biomarker associated with clinical outcome in solid tumors. In this study, for the first time, a correlation was found between the use of pembrolizumab and the change in dNLR and consequently its impact on pCR. A nomogram was constructed to predict the outcome of pCR. [Table: see text]

Phase 3 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in patients with essential thrombocythemia (ET).

TPS6596 Background: ET is a myeloproliferative neoplasm (MPN) driven by mutations in JAK2, CALR, and MPL that is characterized by thrombocytosis and megakaryocyte hyperplasia. Currently available treatments can prevent thrombotic complications but do not substantially alter the natural history of ET. LSD1 is an enzyme that regulates hematopoietic stem and progenitor cell proliferation and is overexpressed in MPNs. In a phase 2 study, the LSD1 inhibitor bomedemstat was generally well tolerated and improved symptoms, durably reduced platelet and white blood cell counts, and reduced mutation burden in patients with ET. Here, we describe the methods for a randomized, open-label, phase 3 study (NCT06079879) that has been designed to evaluate bomedemstat versus best available therapy in patients with ET who had an inadequate response to or were intolerant of hydroxyurea. Methods: Key eligibility criteria include age ≥18 years, a diagnosis of ET per World Health Organization 2016 diagnostic criteria, a bone marrow fibrosis score of grade 0 or 1, a platelet count of &gt;450 x 109/L, and an absolute neutrophil count of ≥0.75 x 109/L. All patients must have a history of inadequate response to or intolerance of hydroxyurea per modified European LeukemiaNet (ELN) criteria. Patients will be randomly assigned 1:1 to bomedemstat 50 mg/day by mouth (starting dose) or investigator’s choice of best available therapy (anagrelide, busulfan, interferon alfa/pegylated interferon alpha, or ruxolitinib). Bomedemstat dose will be titrated to a target platelet count of ≥150 to ≤350 x 109/L. After 52 weeks, patients receiving best available therapy can cross over to bomedemstat at the investigator’s discretion and patients in the bomedemstat arm can continue on treatment (maximum of 156 weeks on study). Randomization will be stratified by hydroxyurea history (inadequate response vs intolerance) and MFSAF v4.0 baseline score (≥4 vs &lt;4). Clinic visits will occur every 2 weeks until week 12 and monthly thereafter. Adverse events will be graded per NCI CTCAE v5.0 criteria and monitored for up to 30 days after last dose of study drug. The primary end point is durable clinicohematologic response rate per modified ELN criteria. Secondary end points are duration of clinicohematologic response, duration of hematologic remission, change from baseline in total symptom and fatigue score per MFSAF v4.0 criteria, change from baseline in total fatigue score per the PROMIS Fatigue SF-7a scale, incidence of thrombotic or major hemorrhagic events, transformation to post-ET myelofibrosis or myelodysplastic syndrome/acute myeloid leukemia, event-free survival, and safety. Exploratory end points include pharmacokinetics, the proportion of patients reporting stability or improvement versus decline on the MSAF v4.0 and PROMIS Fatigue SF-7a domains, and molecular biomarkers. Approximately 300 patients will be enrolled. Clinical trial information: NCT06079879 .

PTPN11variants in chronic myelomonocytic leukemia: Phenotypic and prognostic correlates.

6513 Background: PTPN11 (Ch12q24) is a proto-oncogene that codes for SHP2, a regulatory protein tyrosine phosphatase that impacts RAS/MAPK signaling. Germline variants have been described in juvenile myelomonocytic leukemia, while somatic variants have been associated with inferior survival in acute myeloid leukemia. PTPN11 variants are infrequent in chronic myelomonocytic leukemia (CMML), and their impact on disease phenotype and survival remains unclear. Methods: After IRB approval, 396 molecularly annotated CMML patients at Mayo Clinic were screened for somatic PTPN11 variants within 12 months of diagnosis while still in chronic phase disease. Overall (OS), acute myeloid leukemia (AML)-free survival (LFS), and predictors of survival were estimated using standard statistical measures. Results: 396 patients (median age 71 years; males 67%) with CMML were considered; pathogenic PTPN11 variants were seen in 12 (3%) with a median VAF of 20.5% (range: 4-50): A72T (n = 2), F285S (n = 2), and A72S (n = 2). Variants were most likely to be seen in the N-terminal SH2 domain (n = 7), followed by the PTP domain (n = 6), and the C-terminal SH2 domain (n = 1). PTPN11 variants clustered with CMML-2 (p = 0.02), higher absolute neutrophil count (p = 0.04), peripheral blood (p = 0.06) and bone marrow (p = 0.02) blast %, older age (p &lt;0.01), and were less likely to have SRSF2 comutations (p = 0.02). After a median follow-up of 18 months (range 0-193), 253 (64%) deaths and 68 (17%) AML transformations were recorded. PTPN11 variants negatively and independently impacted both OS (median 13 vs. 31 months; p &lt;0.01) and LFS (AML events: 42% (5/12) vs. 16% (63/384); p &lt;0.01). In age-adjusted multivariate analysis restricted to genetic risk factors, survival was negatively affected by abnormal karyotype and mutations involving PTPN11, DNMT3A, and SETBP1, and positively by TET2 mutations. All but SETBP1 retained significance in the presence of additional independent risk factors, namely male sex (p &lt;0.01) and leukocyte count (p &lt;0.01); HR in the latter analysis was 4.3 for PTPN11, 2.8 for DNMT3A, and 1.6 for abnormal karyotype. A similar analysis for LFS identified, as risk factors, PTPN11 (p = 0.01), DNMT3A (p &lt;0.01), and ASXL1 (p = 0.03) mutations, as well as bone marrow blast % (p &lt;0.01), absolute monocyte count ≥10 (p = 0.02), and immature circulating myeloid cells (p &lt;0.01). Conclusions: The current study identifies PTPN11 and DNMT3A mutations as independent risk factors for both OS and LFS in CMML. In regard to additional genetic risk factors, OS was positively affected by TET2 mutations and negatively by abnormal karyotype, while LFS was negatively affected by ASXL1 mutations.