Higher Absolute Neutrophil Count Research Articles

The Impact of Diabetes Mellitus As Comorbid Condition, in Patients with Lower-Risk Myelodysplastic Syndromes (MDS)— a Study of the European Leukemianet-Based MDS (EUMDS) Registry

Background: Myelodysplastic syndrome is mainly a disease of the elderly, while the prevalence of Diabetes Mellitus (DM) in the aged population is about 25%.Aim: We sought to investigate the impact of DM as comorbid condition on the diagnosis of MDS.Patients and methods: We investigated the clinical and laboratory features at time of MDS diagnosis of 431 DM patients, occurring among a total of 2114 MDS patients registered in the EUMDS registry, and compared them with the non-DM patients. Data were collected by 145 centers located in 16 European countries and Israel.Results: The overall incidence of DM at registration visit was 23%. Higher frequency of DM was observed among MDS patients in Israel (40.3%), Portugal (26.3%) and the Netherlands (25.7%) and lower in Denmark (9.3%), Serbia (10.5%) and Romania (13.6%). Diabetic MDS patients were more commonly male (65.6% vs 60.2%, p=0.01), with higher frequency in Portugal (80%), United Kingdom (76.3%) and Greece (72.9%) and lower in Romania (33.3%), Germany (45.5%) and Israel (54.1%). Higher incidence of DM was encountered among patients with MDS-RA (24.3%, more prominently in the Netherlands, Israel and Spain) and lower among those with RCMD-RS (15.4%). Ring sideroblasts were less commonly encountered among DM patients (24.9% vs 29.5%, p: n.s.) and DM patients had a greater proportion of high MDS-CI risk than non-DM (9% vs 4.8%, p<0.001). The Performance Status (Karnofsky scale) was worse in DM than in non-DM patients (“able” persons 69.1% vs 79.4%, p<0.01). Moreover, DM patients were besides antidiabetic treatment more commonly receiving antiplatelet, anticoagulant and antihypertensive drugs, as well as proton pump inhibitors. No significant difference in the prognostic categorization distribution according to IPSS, WPSS or IPSS-R, between DM and non-DM patients was observed. DM patients were more anemic at diagnosis of MDS (Hb: 10.1±1.7 vs 10.3±1.9 g/dl, p=0.03), had lower MCV (95.5±9.6 vs 98.1±10.6 fl, p<0.01), higher WBC count (5.6±3.3 vs 5.0±3.0 x 109/l, p<0.001), and higher absolute neutrophil count (3.3±2.5 vs 2.8±2.2 x 109/l, p<0.001). No significant difference in baseline platelet counts and in the percentages of patients, exhibiting 0, 1, 2 or 3 cytopenias, between DM and non-DM patients was noted. However, DM patients had higher mean serum creatinine levels (102±65 vs 89±35 μmol/l, p<0.001) and among them there was a significant negative correlation between Hb and serum creatinine levels (r= -0.131, p=0.02). All three iron status parameters (serum iron, transferrin saturation and serum ferritin levels were significantly decreased among DM-patients, implying a possible influence of DM on iron metabolism. Serum EPO levels were not significantly different between the two groups, nevertheless, considering that diabetic MDS patients were more anemic, it could be assumed that they might exhibit somewhat blunted response, probably as a result of some degree of impairment of their renal function. Finally, patient-reported Quality of Life, using the EQ-5D tool was significantly lower among DM-, compared to non-DM patients (0.70±0.24 vs 0.75±0.22, p<0.001).Conclusions: Diabetes Mellitus may modulate the common presenting features of MDS, and since some degree of normocytic, normochromic anemia is commonly associated with this disease, special attention is warranted to discriminate the real MDS patients among the diabetic patient population. DisclosuresFenaux:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Sanz:Gamida Cell: Research Funding. Germing:Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Almeida:Novartis: Consultancy; Celgene: Consultancy; Bristol Meyer Squibb: Honoraria; Alexion: Honoraria; Servier: Consultancy. Guerci-Bresler:BMS: Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau.

Bvgp: A Novel Protocol for Hodgkin's with Excellent Response, Minimal Acute Toxicities and Reduced Risk of Late Effects

Pediatric and Young Adult Hodgkin lymphoma (HL) has a five-year survival rate over 90%. The downside is use of chemotherapy with a lifetime risk of cardiac deaths, second malignancies, pulmonary disease and infertility. Because of effective salvage therapy, ultimate outcomes may be improved by using effective but less toxic initial therapy. To this end, we have piloted a regimen in low and intermediate risk HL using agents not known to be associated with significant late effects. The BVG regimen {bortezomib 1.3 mg/m2 IV day 1,4,8,11; vinorelbine (25 mg/m2 IV day 1,8); gemcitabine (1000 mg/m2 IV day 1,8) every 21 days} was derived from BIGEV [Ding 2009] with elimination of ifosfamide, etoposide and prednisone. Initial use was to consolidate 3 patients after ABVE-PC. Subsequently we treated 5 newly diagnosed patients with non-bulk stage IIA (n=4) or IIB (n=1) HD. Two received BVG and 3 received BVGP with the addition of prednisone (20 mg/m2/dose PO BID x 11 days). Nausea was mild and controlled with 5HT3 antagonists and scopolamine patch. Pegfilgrastim was not necessary due the high absolute neutrophil count nadir (median 1.16 & minimum 0.56 x 109/L). There were no episodes of febrile neutropenia, infections or need for transfusions. There were no significant abnormalities in electrolytes, renal or liver function tests. No patients had any hair loss. One patient developed sensory neuropathy, after dose 8 of bortezomib, that responded to gabapentin and a switch to subcutaneous administration. Newly diagnosed patients were all PET negative after 1 or 2 cycles and remained PET negative at the end of four cycles of therapy. Status of the five newly diagnosed patients ages 10 to 18 is: one is still on therapy; three in remission at 158, 312, 1015 days; one relapsed at 861 days in previous disease sites. This retrospective chart review was approved by Children's Minnesota IRB. For each patient an in depth discussion was held on the benefits and risks of BVGP vs. standard therapy. The chief barrier to use of the protocol was insurance coverage for bortezomib in patients under the age of 18. We hope this abstract will provide early evidence to allow expansion of this pilot experience leading to a randomized trial comparing BVGP with current chemotherapy for low and intermediate Young Adult and Pediatric HL. DisclosuresNo relevant conflicts of interest to declare.

Neutrophil extracellular traps (NETs) and thrombosis (Thr) in pancreaticobiliary cancer (PBC).

e16230 Background: NETs are linked to tissue damage, Thr and cancer progression. Detection of NETs in pancreatic cancer (PC) tissue and NET products in plasma, such as citrullinated Histone 3 (cit-H3) and myeloperoxidase (MPO), can predict survival. A robust biomarker to identify PC patients that may benefit from prophylactic antithrombotic interventions is still lacking. We hypothesized that NET products can predict PC patients at risk of poor outcomes. Methods: Frozen plasma collected on diagnosis from a cohort of 117 patients with HPBC (69% with PC) with known tissue factor (TF) levels was analyzed for MPO and cit-H3 by ELISA. Plasma MPO is a marker of neutrophil degranulation while cit-H3 is a more specific marker of NETosis. Univariate association of clinical variables, TF, cit-H3, MPO with overall survival (OS) was performed. For multivariable analysis, Cox proportional hazards regression model and backward stepwise selection based on the Bayesian information criterion (BIC) were used. Results: We observed a strong correlation between MPO and cit-H3. MPO also correlated with TF. Only TF showed a trend with association with the risk of Thr (p=0.053). Results of the multivariable model for OS are presented in the table (all patients and stratified by Thr status). High absolute neutrophil count (ANC) predicted worse OS only in patients without Thr. Increased cit-H3 was associated with worse OS. Higher MPO predicted worse OS in stage IV patients, which is in contrast to their relationship in stage I-III patients, where increased MPO was associated with improved OS. This interaction effect is stronger in patients with thrombosis. Conclusions: Plasma cit-H3, a systemic marker of NETosis, was associated with worse OS in PBC. Significant MPO by stage interaction implies a differential association of MPO with the OS among patients in different cancer stages. The activation status of neutrophils, including degranulation and NETosis, may be an important predictive biomarker for OS in patients with HPBC with interactions with both stage and Thr. Prospective studies to confirm and extend our findings are ongoing.[Table: see text]

Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma.

PurposeWe performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma.Materials and MethodsThe study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed.ResultsAn ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC.ConclusionIn neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

The clinical potential of circulating immune cell counts in primary gastric lymphoma

High neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in gastrointestinal tract cancers. This study explores the clinical value of NLR, in addition to absolute lymphocyte count (ALC) and other hematologic parameters in association with distant metastases and OS in primary gastric lymphoma (PGL) patients. Clinical data of 139 PGL patients who received treatment at King Hussein Cancer Center (KHCC), Amman-Jordan were retrospectively evaluated. Using data from complete blood count (CBC) tests, the following hematologic parameters: absolute neutrophil count (ANC), ALC, absolute eosinophil count (AEC), absolute monocyte count (AMC), NLR, platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) were assessed in association with the following clinical outcomes: presence or absence of baseline distant metastases and OS. We conducted univariate and multivariate analyses assessing the various hematologic parameters in association with distant metastases. Univariate and multivariate analyses indicated that patients with an elevated NLR (>3.14) displayed more baseline distant metastases compared to patients with a low NLR (≤3.14), (P value: 0.02 and 0.018, respectively). High baseline ALC (>1,819/µL) was associated with lower baseline distant metastases (P value: 0.04). In the OS analysis, high baseline ANC (>5,100/µL), NLR (>2.75), and PLR (>0.16) were associated with poor OS, (P value: 0.027, 0.016, and 0.011 respectively). High NLR and ALC were associated with baseline distant metastases. High baseline ANC, NLR, and PLR were associated with poor OS. Hematologic parameters might be potentially helpful in assessing and correlating NLR with the response success to treatment in PGL.

The inflammatory markers of multisystem inflammatory syndrome in children (MIS-C) and adolescents associated with COVID-19: A meta-analysis.

To conduct a systematic review and meta‐analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS‐C) versus severe/non‐severe COVID‐19, severe MIS‐C versus non‐severe MIS‐C, and among age groups of MIS‐C. Nine databases were searched for studies on inflammatory markers of MIS‐C. After quality checks, data were pooled using a fixed or random effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C‐reactive protein (CRP), procalcitonin (PCT), ferritin, D‐dimer, lactate dehydrogenase (LDH), fibrinogen, and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty‐one studies with 1735 participants yielded 787 MIS‐C patients. Compared to non‐severe COVID‐19 patients, MIS‐C patients had lower ALC and higher ANC, CRP, and D‐dimer levels. Compared to severe COVID‐19 patients, MIS‐C patients had lower LDH and PLT counts and higher ESR levels. Severe MIS‐C patients had higher levels of WBC, ANC, CRP, D‐dimer, and ferritin than non‐severe MIS‐C patients. For MIS‐C, younger children (0–5 years) had lower CRP and ferritin levels than middle‐aged/older children/adolescents. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS‐C and the associated disorders.

Assessing Safe Discharge Criteria for Pediatric Oncology Patients Admitted for Febrile Neutropenia.

Recent studies suggest outpatient therapy, oral antibiotics, or earlier discharge could be appropriate in some pediatric patients admitted with febrile neutropenia; supporting data are lacking. Retrospective chart review of patients admitted from September 2005 through October 2016 identified 131 "early discharge" febrile neutropenia admissions with discharge absolute neutrophil count (ANC) <500/µl and negative cultures. All were afebrile and discharged without outpatient antibiotics. Eleven of 131 patients (8%) were readmitted. Two patients called back for late positive cultures. Nine were readmitted with febrile neutropenia; 2 had positive cultures on readmission. All 4 patients with positive cultures were safely treated with appropriate antibiotics. The remaining 7 patients had uneventful readmissions. Average ANC (SD) at discharge was lower for patients readmitted versus those not readmitted (69 [70] vs. 196 [145], P≤0.001), as was absolute phagocyte count (APC) at discharge (97 [82] vs. 453 [431], P≤0.001). APC on admission was not significantly lower for those readmitted (165 [254] vs. 321 [388], P=0.09). Few patients required readmission; those with bacterial infections were easily identified and appropriately treated. Higher ANC or APC criteria for discharge would increase length of hospital stay without decreasing morbidity. A subset of patients admitted with febrile neutropenia can be safely discharged before count recovery without oral antibiotics.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium

BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701

Neutrophil lymphocyte ratio (NLR) is inversely proportional to cycle threshold value of orf1a gene in RTPCR may be used as biomarker in Covid19 patients

Corona virus disease (COVID-19) is an infectious disease caused by a newly discovered corona virus. The virus that causes COVID-19 is mainly transmitted through droplets generated when an infected person coughs, sneezes, or exhales. These droplets are too heavy to hang in the air, and quickly fall on floors or surfaces. A person can be infected by breathing in the virus if the person is within close proximity of someone who has COVID-19, or by touching a contaminated surface and then your eyes, nose or mouth. This study was conducted to find the correlation between Neutrophil Lymphocyte Ratio (NLR) and Cycle Threshold Values of RTPCR in Covid-19 infected patients. This study was conducted in a Diagnostic Centre, located in Kolkata. Data was collected from patients of Covid-19 between October’20to December’20, positive for Covid-19 Infection. Basic demographic data was collected from Laboratory Information System (LIS) of the diagnostic centre. Whole blood EDTA sample were collected to analyze the features of WBC (Neutrophil and Lymphocyte) Total 500 patients were studied for hematological parameters (NLR). Demographic data revealed age range from 10 years to 80 years. Males constituted 360(72%) and females 140(28%). Leukocyte Count showed Leucocytosis was observed in 60% of patients, high absolute neutrophil count in 5%, high Neutrophil Lymphocyte Ratio (NLR) in 55% patients.

Is Multidrug Resistance in Acute Otitis Media with Streptococcus pneumoniae Associated with a More Severe Disease?

Objectives: Streptococcus pneumoniae is the leading bacterial etiologic agent in acute otitis media (AOM), and it produces a more severe inflammatory response than other otopathogens. Additionally, the presence of multidrug-resistant (MDR) S. pneumoniae is an important issue in the management of AOM. The present pilot study aimed to ascertain whether MDR S. pneumoniae is associated with a higher inflammatory response and/or a more severe disease. Methods: This was a prospective, single-center study on nonpneumococcal conjugate vaccine-immunized pediatric patients with severe AOM. Demographic and clinical characteristics were recorded. Middle ear fluid was obtained and cultured for each patient; antibiotic-resistance profiling was tested for S. pneumoniae isolates. The C-reactive protein (CRP) level and complete blood count were determined. Patients with positive middle ear fluid culture for S. pneumoniae were divided into 2 groups according to antibiotic resistance profile: MDR and non-MDR. Results: MDR S. pneumoniae was identified in 15 (35.7%) of the 42 eligible patients. Children in this group had significantly higher CRP levels (72.23 ± 62.92 vs. 14.96 ± 15.57 mg/L, p < 0.001), higher absolute neutrophil count (8.46 ± 3.97 vs. 5.22 ± 4.5 × 10³/mm³, p = 0.004), higher percentage of neutrophils (52.85 ± 13.49% vs. 38.34 ± 16.16%, p = 0.004), and were more prone to develop acute mastoiditis (p = 0.01). Receiver operating characteristic analysis identified CRP as the best biomarker to discriminate between the 2 groups of patients (AUC = 0.891). Conclusion: MDR S. pneumoniae was associated with a more severe inflammatory response and a higher incidence of mastoiditis.

536. HIV Patients with COVID-19 in the Bronx: A Retrospective Cohort Study

BackgroundSince the start of the pandemic there has been limited data on mortality in people living with HIV (PLWH) who have Coronavirus Disease 2019 (COVID-19) in the United States (US). We conducted a retrospective review to investigate potential risk factors associated with survival and need for medical ventilation for PLWH and COVID-19.MethodsThis is a retrospective observational cohort from a large academic center across three campuses, conducted from January 1, 2020 to April 30, 2020. Thirty day readmissions were observed from January 1, 2020 to May 31, 2020. Our patients were identified by an ICD-10 code (B20) corresponding to HIV and positive SARS-CoV-2 PCR test. As a primary endpoint, we compared survivors vs. non-survivors. As a secondary endpoint, we compared patients who needed mechanical ventilator (MV) vs. those who did not need MV.ResultsSeventy two PLWH (28 female patients (39%), median [IQR] age was 62 [-/+16] years) had positive SARS-CoV-2 PCR tests during this retrospective review. Median CD4+ count was 235 cells/ul and 11 (15%) had an HIV viral load >200 copies/mL. The median length of stay was 5 days and 6 patients were directly discharged from the emergency department. Ten patients were readmitted within 30 days with SARS-CoV-2 – like symptoms and 2 are still inpatient. Twenty patients (27.8%) have expired. All non-survivors that expired had an undetectable HIV viral load (0%, p=0.02). The 11 patients with unsuppressed HIV viral loads at the start of the study period all survived, p=0.02. Non-survivors were more likely to have chronic kidney disease CKD (p< 0.01) acute kidney injury (p< 0.01), higher absolute neutrophils (p< 0.01), and elevated IL-6 levels (p< 0.01) compared to survivors. Fifteen patients (20.8%) required mechanical ventilation (MV), 3 (4.1%) of those patients survived. Patients that required MV were more likely to be male (p=0.01) obese (p< 0.01) and had higher absolute neutrophil counts (p=0.01) versus those that did not need MV. Patients with lower CD4 counts (< 200 cells/uL) did not require more mechanical ventilation (p=0.04).Table 1: Demographics, Primary and Secondary Outcome Results ConclusionPLWH who had COVID-19 had a high mortality rate. Since all the patients who died had an undetectable HIV viral load across CD4 counts, our study suggests that patients with uncontrolled HIV are not at an increased risk of mortality.Disclosures All Authors: No reported disclosures

IMPACT OF COVID-19 ON HEMATOLOGICAL PARAMETERS-A SINGLE CENTRE STUDY, INDIA.

Aims and Objectives: To analyze various hematological parameters in Covid-19 infected patients. Patients/Materials and Methods: This is a retrospective, single centre cross sectional study conducted in a tertiary care hospital, located in a tri-state region. Data was collected from patients admitted in Covid-19 ward and ICU between 28 July to 7 September 2020, confirmed positive for Covid-19 infection. Basic demographic data was collected from Laboratory Information System(LIS) of our hospital . Whole blood EDTA sample sent from Covid-19 ward and ICU were processed in LH780/DXH 500(Beckman coulter) for complete blood counts. Further patients laboratory features were analyzed . Results: Findings of 338 patients, both from ward and ICU, showed varied hematological parameters. Demographic data revealed age range from 1day to 86 years. Males constituted 205(60.65%) and females 133(39.34%).Complete blood count showed Hemoglobin(Hb) concentration ranged from 5.8 -18.5gm/dL and median value 13.6gm/dL. Red cell distribution width(RDW) ranged from 11.4-39.9% with median value of 13.6%. Leucocytosis was observed in 13.9% of patients, high absolute neutrophil count in 15.6% ,high Neutrophil to Lymphocyte ratio(NLR) in 10.05% patients and eosinophil count ranged from 0-15.3%. Conclusion: Baseline alterations in CBC parameters of 10-15% of patients in the present study along with articles reviewed from various countries indicate Covid -19 infection causes systemic infection involving multiple organs and systems.

EPID-08. PRE-SURGERY IMMUNE PROFILES OF ADULT GLIOMA PATIENTS

Abstract Changes in glioma patients’ immune profiles over the course of disease may predict outcomes. DNA based immunomethylomics quantifies blood immune cells based on cell specific DNA methylation signatures. To assess changes in immune profiles, we are longitudinally collecting blood samples from glioma patients pre-surgery and at other clinically relevant time points. Here we report patients’ pre-surgery immune profiles. All patients underwent biopsy or resection of a presumed new glioma or recurrent lower grade glioma. Blood DNA methylation was assessed with Illumina EPIC methylation arrays. Relative cell fractions of CD4, CD8, B-cells, natural killer cells, monocytes, and neutrophils, were estimated via our validated deconvolution algorithm. Total nucleated cell counts from Nexcelom cytometry were used to compute absolute cell counts. Other measures include total lymphocytes, CD4/CD8 ratio, neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR)). The first 125 participants includes 56 newly diagnosed glioblastomas (GBM), 28 newly diagnosed grade II-III gliomas, and 41 recurrent grade II-III gliomas. Median patient age is 49 years. 53 (43%) had recent dexamethasone exposure. In overall non-parametric analyses, most cell subsets, especially CD4, differed across grade, diagnosis group, WHO classification and dexamethasone exposure. In post-hoc pairwise analyses, immune profiles of IDH wildtype GBM patients who had taken dexamethasone differed from patients with GBM or grade II-III glioma who had not taken dexamethasone; they had clinically relevant and statistically significantly lower absolute CD4 counts, total white cell counts, and percent of total lymphocytes, and higher absolute neutrophil counts, NLR and LMR. However, some dexamethasone naïve GBM patients also had altered immune profiles. Comparisons of relative immune cell fractions with those from 454 non-glioma controls from the UCSF Adult Glioma Study showed that across grade and WHO classification, for the most part, immune profiles of glioma patients not exposed to dexamethasone did not differ from controls.

Hematologic Characteristics of Surviving Versus Non-Surviving COVID-19 Patients in Critical Care Units: Inner-City Hospital Experience, Detroit, MI

BackgroundAs the COVID-19 pandemic spread across the US, the city of Detroit rose as one of the earliest infection epicenters in the nation. Henry Ford Hospital serves a diverse multi ethnic population in the inner city and throughout metropolitan Detroit, and thus provided care to a significant percentage of COVID 19 patients in the state of Michigan.Retrospective reviews have described different hematologic abnormalities in patients with COVID-19. Various markers, such as lymphopenia, neutrophilia, elevated ferritin, and DDimer levels have been identified as predictors of poor outcomes, intensive care unit (ICU) admission, and mortality.The aim of this study was to evaluate the impact of hematologic characteristics on the risk of intubation and mortality in our unique patient population infected with COVID-19 who required ICU admission.Methods: This was a retrospective medical record review of adult patients with laboratory-confirmed COVID-19 requiring admission to adult ICU at Henry Ford Hospital in Detroit, MI, from March 1 to April 15, 2020. The main outcomes assessed were death and need for intubation and mechanical ventilation.Results: A total of 229 patients met the study inclusion criteria.Of the 76 surviving patients analyzed, 40 (53%) were men and 36 (47%) were women, including 59 (78%) Black and 11 (14%) White patients. The mean age at presentation was 61 (SD, 15) years. Hypertension was the most common comorbidity (n=65 patients), followed by diabetes (n=39). Most surviving patients (n=60; 79%) were admitted to general practice units (GPU) and then transferred to ICU, while 49 (64%) patients required intubation.Among the 153 patients who died, 95 (62%) were men and 58 (38%) were women, with 41 (27%) being White and 99 (65%) Black. The mean age at presentation was 69 years (SD, 14.3). Hypertension was the most common presenting co-morbidity (n=118), followed by diabetes (n=72). More non-surviving patients were admitted directly to the ICU (n=71; 46%) and/or required intubation (n=147; 96%).Hematologic laboratory findings of the studied patients are represented in Table 1.Multivariate analysis of variables predictive of death and intubation are summarized in Table 2.Logistic modeling revealed an 18% increase in the odds of death and a 17% increase in odds of intubation for each unit increase in WBC. Also, for each unit increase in ANC, there was a 17% increase in odds of death and 21% increase in odds of intubation.Conclusions:Among patients with COVID-19 who required admission to ICU, Black patients were over-represented. Coronary artery disease (CAD), older age, and a lower oxygen saturation (SpO2) on initial triage in the emergency department were associated with increased mortality. A higher absolute neutrophil count (ANC) and white blood cell count (WBC) was associated with higher risk of intubation and death. Male sex and direct ICU admission were predictors of increased risk of intubation - and these patients were more likely to die. Contrary to other reports, lymphopenia did not increase odds of intubation or death in ICU, and neither the serum ferritin nor DDimer levels on admission were discriminators for death; however, higher peak levels during the hospitalization were linked to increased mortality.Inner city Black populations with advanced age, multiple co-morbidities, and COVID-19 may be at increased risk for ICU admission, and thereby at an increased risk of death. However, not all hematologic characteristics are generalizable with regard to intubation and mortality in ICU.DisclosuresNo relevant conflicts of interest to declare.

Multivariable Analysis of 169 Cases of Advanced Cutaneous Melanoma to Evaluate Antibiotic Exposure as Predictor of Survival to Anti-PD-1 Based Immunotherapies.

Recently antibiotic exposure has been associated with worse outcomes in patients undergoing treatment with antibodies directed against programmed cell death protein-1 (PD-1). We reviewed data of 1264 patients enrolled at Melanoma Skin and Ocular Tissue Repositories at University of Iowa Hospitals and Clinic. Reviewed data included patient demographics, prior medical history, baseline hematologic and disease parameters and outcomes including progression-free survival (PFS) and overall survival (OS). Cox regression models were used to determine predictive markers. Overall, 169 patients with advanced cutaneous melanoma received anti-PD-1 based therapies. Median follow up was 18.46 (range 0.89 to 62.52) months. On multivariable analysis brain metastasis, higher absolute neutrophil count (ANC) and lower absolute lymphocyte count were associated with poorer PFS while brain and liver metastasis and lower albumin were associated with poorer OS. Prior antibiotics, radiation as well as age, gender, basal metabolic index (BMI), smoking status, BRAF mutation, line of therapy (first or latter), prior treatments (ipilimumab or BRAF inhibitors), hemoglobin, neutrophil-to-lymphocyte ratio, white blood cell, platelet and eosinophil counts were not associated with PFS or OS in multivariable analysis. Contrary to some prior studies BMI, radiation, and antibiotics were not associated with PFS or OS.

The clinical value of peripheral immune cell counts in pancreatic cancer.

Elevated neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in pancreatic cancer. We aim to investigate the association of the various hematologic markers, in particular NLR among others, with distant metastases, a common feature in pancreatic cancer. Clinical data from 355 pancreatic cancer patients managed at King Hussein Cancer Center (Amman-Jordan) have been reviewed. We examined the relationship between absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophilic count (AEC), absolute monocytic count (AMC), NLR, monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) with the presence of baseline distant metastases and OS. Receiver Operating Characteristic (ROC) curve analysis was plotted to identify the NLR optimum cutoff value indicative of its association with distant metastases. On univariate and multivariate analyses patients whom on presentation had high NLR (≥3.3) showed more baseline distant metastases compared to patients with low NLR (<3.3), (p-value: <0.0001 and <0.0001, respectively). Patients with high baseline ANC (≥5500/μL), AMC (≥600/μL), MLR (≥0.3) had more baseline distant metastases in comparison to patients with lower values (p-value: 0.02, 0.001, and <0.0001, respectively). High ANC, NLR, MLR, and PLR and low ALC were associated with poorer OS, (p-value: <0.0001, <0.0001, <0.0001, 0.04, and 0.01, respectively). This study presents additional evidence of the association of some of the hematologic markers; in particular ANC, NLR, AMC, and MLR, with baseline distant metastases and poor outcome in pancreatic cancer. Whether these immune phenomena can help in identifying patients at higher risk for the subsequent development of distant metastases is unknown.

Pegfilgrastim on-body injector: Post-market performance analysis.

e19226 Background: Granulocyte colony-stimulating factors (G-CSF) are widely used in medical oncology for the prevention of neutropenia and its complications. On-body injectors (OBI) have an advantage over the traditional injection (TI) method of not requiring a second visit to the oncology clinic the day after chemotherapy, but these devices are subject to failure. The objective of this study was to assess the efficacy of OBIs in the real world. Methods: Adult women with breast cancer diagnosed between June 2015 and June 2016 treated with cytotoxic chemotherapy and a G-CSF were retrospectively identified from the medical records of Henry Ford Hospital (Detroit, MI, USA). The primary outcome was the incidence of severe neutropenia (SN), defined as an absolute neutrophil count (ANC) ≤500. Secondary outcomes included incidence of neutropenia (ANC ≤1500), neutropenic fever, and mortality. A secondary analysis of the data was performed to identify predictors of SN. Results: A total of 837 cycles of chemotherapy were analyzed. The OBI was used in 395 cycles and the TI in 442. The OBI group had patients that were older, had higher ANC, were more often black, had worse performance status, and were more often smokers. The incidences of SN, neutropenic fever and neutropenia were not different between groups (Table). Mortality was not different between groups when adjusted for confounding variables (OR 1.8, 95% CI 0.9-3.6, p=0.09). Patients with a lower baseline ANC and white ethnicity were at a higher risk for SN. TAC (docetaxel, doxorubicin and cyclophosphamide combined) carried the highest risk for SN among the chemotherapy regimens used. Conclusions: There was no difference in the efficacy of the OBI and TI methods for preventing SN, neutropenic fever, neutropenia, and death. Independent predictors of SN included the chemotherapy regimen used, baseline ANC and ethnicity. [Table: see text]

Abstract P2-17-03: Real-world benefit of CDK4/6 inhibitor and endocrine therapy combination in metastatic breast cancer and correlation with neutropenia

Abstract Background: Combination of a CDK4/6 inhibitor plus endocrine therapy has been shown to significantly improve the progression free survival (PFS) in patients with hormone-receptor (HR)+, HER2- metastatic breast cancer. The aims of this retrospective study was: 1) to evaluate the real-world benefit of palbociclib plus endocrine therapy as the first line treatment in HR+, HER2- metastatic breast cancer (mBC) and 2) to correlate efficacy of the combination with neutropenia (which is a common toxicity of CDK4/6 inhibitors). Methods: This study included HR+, HER2- advanced mBC patients who were treated with palbociclib plus an endocrine therapy (mainly letrozole) at Moffitt Cancer Center between January 1, 2015 and March 1, 2018. The PFS was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were investigated using the univariable and multivariable Cox models. Results: A total of 165 patients were included in this retrospective cohort study. The median PFS of the full cohort was 24.19 months (95% CI 18.93 to not reached). For patients with bone metastasis only (n = 54), the median PFS was not reached (95% CI 18.21 to not reached). For patients with non-bone-only metastasis (n = 111), the median PFS was 24.19 months (95% CI 16.33 to 33.82). Patients with higher absolute neutrophil counts (ANC) are at high risk of disease progression (HR 1.15; 95% CI 1.03 to 1.29, p = 0.013). We did not find a significant association between the value of NLR and the risk of disease progression (HR 1.07 95% 0.97 to 1.18, p = 0.203). Both ANC and NLR were used as a time dependent variable. Conclusion:The effectiveness of palbociclib plus letrozole in the treatment of HR+, HER2- metastatic breast cancer in the real-world setting was found to be similar to the results from the PALOMA-2 trial. In addition, patients with a higher ANC were found to have a higher risk for early disease progression. This has implication for clinical practice [i.e., frequent dose delay and/or dose reduction based on ANC threshold of 1000/uL may not be an optimal approach. Since infection is rare, it is reasonable to reduce this threshold to a lower level such as 750-800/uL]. Citation Format: Dakota Jenneman, Xiaojun Zhong, Junjie Ma, Weihong Sun, Heather Han, Hatem Soliman, Loretta Loftus, Ricardo Costa, Avan Armaghani, Aixa Soyano, Brian Czerniecki, M. Catherine Lee, John Kiluk, Nazanin Khakpour, Susan Hoover, Christine Laronga, Hung T Khong. Real-world benefit of CDK4/6 inhibitor and endocrine therapy combination in metastatic breast cancer and correlation with neutropenia [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-03.

Effects of Hydroxyurea Treatment on Malaria Infections in Sub-Saharan Africa

Introduction. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) is a prospective multicenter open-label trial that has already demonstrated hydroxyurea treatment at maximum tolerated dose (MTD) is safe, feasible, and offers major benefits for children with sickle cell anemia living in sub-Saharan Africa (Tshilolo et al, NEJM 2019;380:121-131). One unexpected benefit was a significant reduction in the number of malaria infections, including those with Grade 3 severity or above, across four trial sites in varied epidemiological settings. The overall rate of symptomatic malaria infections decreased from 46.9 events per 100 patient-years during screening to 22.9 events per 100 patient-years on treatment, an incidence rate ratio of 0.49 (95% confidence intervals [CI] = 0.37-0.66). This decreased rate of malaria was observed during the first 12 months of treatment, but declined further between Months 12-36, after the children had dose escalation to achieve hydroxyurea MTD at 22.5 mg/kg/day. Potential mechanisms of malaria protection remain unknown at this time, but could relate to both patient characteristics as well as treatment-related laboratory changes in hemoglobin (Hb), mean corpuscular volume (MCV), absolute neutrophil count (ANC), or fetal hemoglobin (HbF). Methods. Malaria infections were recorded in the REACH REDCap electronic database. Using several methods for recurrent events, with time-varying predictors as well as landmark analysis, associations with infections recorded during study treatment were assessed for multiple variables including trial site, high or low malaria season, age, gender, spleen status, hydroxyurea dose, MTD status, latest laboratory values (Hb, MCV, ANC, and HbF, all measured at least 15 days prior to the onset of the infection), as well as genetic modifiers alpha-thalassemia and G6PD deficiency. Univariate relationships were assessed using the Anderson-Gill model, followed by multiple regression to estimate Hazard Ratios (HR) with 95% CI's. Additional analyses were performed using a gap-time model that resets the clock after each infection, as well as using only the first infection in each participant; the subset of 200 acute blood-smear proven malaria infections was also analyzed separately. Results. A total of 635 children were enrolled in REACH and eligible for analysis, of whom 606 started hydroxyurea treatment. There were 333 malaria infections recorded during 1580 patient-years of observation, including 50 during screening and 283 on treatment, of which 200 had documented positive blood smears at the clinical site. Significant associations for malaria risk were identified with higher ANC (HR = 1.06 per 1 x 109 neutrophils/L, CI = 1.02-1.10, P=0.005), higher MCV (HR = 1.01 per fL, CI = 1.00-1.02), and palpable splenomegaly (HR 1-4cm = 1.73, CI = 1.22-2.45, P= 0.002, HR ≥5cm = 1.52, CI = 1.04-2.21, P=0.03). In multiple regression, the latest ANC and MCV, as well as splenomegaly remained significant but higher HbF was also associated with more malaria (HR = 1.02 per %HbF, CI = 1.00-1.03, P=0.03). These trends were consistent when using the landmark, gap-time and first infection analytical approaches. Analysis of only documented blood-smear positive malaria infections again identified higher ANC, MCV, and splenomegaly as risk factors, but found no association with HbF. Achieving MTD was found to confer significant protection against documented malaria infections (HR = 0.62, CI=0.39-1.00, P=0.048). Conclusion. Hydroxyurea treatment in children with sickle cell anemia living in sub-Saharan Africa is associated with a decreased risk of malaria infections, particularly after achieving MTD. The mechanisms by which hydroxyurea protects against malaria are likely multi-factorial, but do not appear to be related to HbF induction, as higher HbF values were not protective and in some analyses were a risk factor. However, a higher ANC was significantly associated with malaria risk in all models and analyses; since hydroxyurea treatment lowers the ANC, dose escalation to MTD may confer protection against malaria infection by reducing inflammation. Spleen status is also crucial and the role of splenomegaly as a risk factor for malaria requires further investigation. Disclosures Ware: Novartis: Other: DSMB; Agios: Membership on an entity's Board of Directors or advisory committees; Nova Laboratories: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Addmedica: Other: Research Drug Donation; Bristol Myers Squibb: Other: Research Drug Donation; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Paroxysmal Nocturnal Hemoglobinuria Clones Are Infrequent in Hepatitis-Associated Aplastic Anemia at the Time of Diagnosis

Aplastic anemia (AA) is an immune-mediated bone marrow failure, resulting in reduced number of hematopoietic stem and progenitor cells and pancytopenia. The presence of paroxysmal nocturnal hemoglobinuria (PNH) clone in AA usually suggests an immunopathogenesis in patients. However, when and how PNH clone emerge in AA is still unclear. Hepatitis associated aplastic anemia (HAAA) is a special variant of AA with a clear disease course and relatively explicit immune pathogenesis, thus serves as a good model to explore the emergence and expansion of PNH clone. To evaluate the frequency and clonal evolution of PNH clones in AA, we retrospectively analyzed the clinical data of 90 HAAA patients that were consecutively diagnosed between August 2006 and March 2018 in Blood Diseases Hospital, and we included 403 idiopathic AA (IAA) patients as control. PNH clones were detected in 8 HAAA patients (8.9%,8/90) at the time of diagnosis, compared to 18.1% (73/403) in IAA. Eight HAAA patients had PNH clone in granulocytes with a median clone size of 3.90% (1.09-12.33%), and 3 patients had PNH clone in erythrocytes (median 4.29%, range 2.99-10.8%). Only one HAAA patients (1/8, 12.5%) had a PNH clone larger than 10%, while 24 out of 73 IAA patients (32.9%) had larger PNH clones. Taken together, we observed a less frequent PNH clone with smaller clone size in HAAA patients, compared to that in IAAs. We next attempted to find out factors that associated with PNH clones. We first split patients with HAAA into two groups based on the length of disease history (≥3 mo and &lt; 3mo). There were more patients carried PNH clone in HAAA with longer history (21.4%, 3/14) than patients with shorter history (6.6%, 5/76), in line with higher incidence of PNH clone in IAA patients who had longer disease history. Then we compared the PNH clone incidence between HAAA patients with higher absolute neutrophil counts (ANC, ≥0.2*109/L) and lower ANC (&lt; 0.2*109/L). Interestingly, very few VSAA patients developed PNH clone (5%, 3/60), while 16.7% (5/30) of non-VSAA patients had PNH clone at diagnosis. We monitored the evolution of PNH clones after immunosuppressive therapy, and found increased incidence of PNH clone over time. The overall frequency of PNH clone in HAAA was 20.8% (15/72), which was comparable to that in IAA (27.8%, 112/403). Two thirds of those new PNH clones occurred in non-responders in HAAA. In conclusion, PNH clones are infrequent in HAAA compared to IAA at the time of diagnosis, but the overall frequency over time are comparable between the two groups of patients. In SAA/VSAA patients who are under the activated abnormal immunity, longer clinical course and relatively adequate residual hematopoietic cells serve as two important extrinsic factors for HSCs with PIGA-mutation to escape from immune attack and to expand. Disclosures No relevant conflicts of interest to declare.