DIC Complicating APL Successfully Treated With Recombinant Thrombomodulin Alfa.

Weight Increase during Induction Therapy Predicts Intensive Care Unit (ICU) Transfer in Patients (Pts) with Acute Promyelocytic Leukemia (APL)

Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML-RAR alpha fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.

Front Line Treatment of Elderly Patients with Acute Promyelocytic Leukemia: Long-Term Results of the German AML Cooperative Group

A positive association between white blood cell count and carotid atherosclerosis has been reported. Our previous study also found an inverse association between height and carotid atherosclerosis in overweight but not non-overweight men. However, no studies have reported on the association between high white blood cell (WBC) count and height accounting for body mass index (BMI) status. We conducted a hospital-based general population cross-sectional study of 3016 Japanese men aged 30-59years undergoing general health check-ups between April 2013 and March 2014. High WBC count was defined as the highest tertiles of WBC count among total subjects. Independent of classical cardiovascular risk factors, height was found to be inversely associated with high WBC count, especially for subjects with a BMI≥23kg/m2. The classical cardiovascular risk factors adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of high WBC count for an increment of one standard deviation (SD) in height (5.7cm) were 0.91 (0.83-0.99) for total subjects, 1.00 (0.86-1.15) for subjects with a BMI<23kg/m2 and 0.86 (0.77-0.96) for subjects with a BMI≥23kg/m2. Independent of classical cardiovascular risk factors, height was found to be inversely associated with high WBC count, especially for those with a BMI≥23kg/m2. Compared to high stature, short stature appears to convey an inflammatory disadvantage among Japanese men, especially those with a BMI≥23kg/m2.

In standard-risk acute promyelocytic leukemia, recent results have shown that all-trans retinoic acid plus arsenic trioxide combinations are at least as effective as classical all-trans retinoic acid plus anthracycline-based chemotherapy while being less myelosuppressive. However, the role of frontline arsenic trioxide is less clear in higher-risk acute promyelocytic leukemia, and access to arsenic remains limited for front-line treatment of standard-risk acute promyelocytic leukemia in many countries. In this randomized trial, we compared arsenic, all-trans retinoic acid and the “classical” cytarabine for consolidation treatment (after all-trans retinoic acid and chemotherapy induction treatment) in standard-risk acute promyelocytic leukemia, and evaluated the addition of arsenic during consolidation in higher-risk disease. Patients with newly diagnosed acute promyelocytic leukemia with a white blood cell count <10x109/L, after an induction treatment consisting of all-trans retinoic acid plus idarubicin and cytarabine, received consolidation chemotherapy with idarubicin and cytarabine, arsenic or all-trans retinoic acid. Patients with a white blood cell count >10x109/L received consolidation chemotherapy with or without arsenic. Overall, 795 patients with acute promyelocytic leukemia were enrolled in this trial. Among those with standard-risk acute promyelocytic leukemia (n=581), the 5-year event-free survival rates from randomization were 88.7%, 95.7% and 85.4% in the cytarabine, arsenic and all-trans retinoic acid consolidation groups, respectively (P=0.0067), and the 5-year cumulative incidences of relapse were was 5.5%, 0% and 8.2%. (P=0.001). Among those with higher-risk acute promyelocytic leukemia (n=214), the 5-year event-free survival rates were 85.5% and 92.1% (P=0.38) in the chemotherapy and chemotherapy plus arsenic groups, respectively, and the corresponding 5-year cumulative incidences of relapse were 4.6% and 3.5% (P=0.99). Given the prolonged myelosuppression that occurred in the chemotherapy plus arsenic arm, a protocol amendment excluded cytarabine during consolidation cycles in the chemotherapy plus arsenic group, resulting in no increase in relapse. Our results therefore advocate systematic introduction of arsenic in the first-line treatment of acute promyelocytic leukemia, but probably not concomitantly with intensive chemotherapy, a situation in which we found myelosuppression to be significant. (ClinicalTrials.gov Identifier: NCT00378365)

Introduction:Admission white blood cell (WBC) count and thrombosis in myocardial infarction (TIMI) risk score have been associated with adverse outcomes after acute myocardial infarction (AMI). This study investigated the joint effect of WBC count and TIMI risk score on predicting in-hospital outcomes in patients with AMI.Materials and Methods:WBC count and TIMI risk score were measured at the time of hospital admission in 70 patients with AMI. Echocardiogram was done on prior to discharge by a cardiologist and ejection fraction (EF) was determined according to the Simpson formula. Patients were stratified into tertiles (low and high) based on WBC count and TIMI risk score.Results:Patients with a high WBC count had a 5.0-fold increase in-hospital congestive heart failure and 2.2 increases in mortality compared with those with a low WBC count. Patients with a high TIMI risk score had a 10-fold increase in congestive heart failure presentation and mortality compared with those with a low TIMI risk score. When a combination of different strata for each variable was analyzed, a stepwise increase in mortality was seen. There were a few number of patients with a high WBC count and low TIMI risk score or with a low WBC count and high TIMI risk score. These patients had an intermediate risk, whereas those with a high WBC count and TIMI risk score had the highest risk.Conclusion:These findings suggested that a simple combination of WBC count and TIMI risk score might provide further information for predicting outcomes in patients with AMI.

Impact of FLT3 Mutation Status and Other Genetic Parameters In Acute Promyelocytic Leukemia (APL) with t(15;17)(q22;q12)/PML-RARA.

To explore the efficacy of treatment for childhood acute promyelocytic leukemia (APL) with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) for remission induction, we reviewed the clinical course and outcome of 37 children with APL from January 1999 to December 2003. Among the 37 children (≤14years) with newly diagnosed APL, we applied treatments that consisted of ATRA alone or in combination with As(2)O(3) in induction followed by consolidation and maintenance treatment. Overall, 35 (94.6%) of 37 children achieved complete remission (CR). Two patients died of intracerebral hemorrhage on days 1 and 2. The 5-year estimates of event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) rates for the 37 patients were 79.2, 83.7, and 91.5%, respectively. There were 27 patients with white blood cell (WBC) count lower than 10×10(9)/L. In 27 patients with a WBC count <10×10(9)/L, 17 patients (group-I) were treated with ATRA alone and 10 patients (group-II) were treated with ATRA which was switched to As(2)O(3) due to the side effects of ATRA. Although the 5-year estimate of DFS between group-I and group-II showed no significant difference (P=0.108), the DFS rate improved by 25% in group-II. Our results suggest that the combination of As(2)O(3) and ATRA might decrease the relapse rate compared with ATRA alone in induction therapy for childhood APL, at least in those with a WBC count less than 10×10(9)/L.

Stroke-associated pneumonia (SAP) often occurs after ischemic stroke. A deterioration in SAP manifests itself in a decreased partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, indicating gas exchange dysfunction. We aimed to investigate independent predictors and outcomes of SAP with low PaO2/FiO2 ratio among patients with acute large vessel occlusion (ALVO) undergoing endovascular therapy. We retrospectively analyzed the prospective data of consecutive adult post-interventional patients with ALVO admitted to neuro-intensive care units in Wuhan No. 1 Hospital from December 2020 to December 2022. Patients developing SAP without coronavirus disease 2019 were included in this study and divided into two subgroups: PaO2/FiO2 ratio > 240 and ≤ 240. The primary outcome was favorable neuro-function at 90 days (modified Rankin Scale score of 0-2). Secondary outcomes included hospitalization days, occurrence of symptomatic intracerebral hemorrhage, and 90-day mortality. The independent risk factors and prognosis for SAP with PaO2/FiO2 ratio ≤ 240 were identified by logistic regression analyses. A total of 159 subjects developing SAP were included in this study: 53 with PaO2/FiO2 ratio > 240 and 106 with ratio ≤ 240. Compared to subjects with PaO2/FiO2 ratio > 240, those with PaO2/FiO2 ratio ≤ 240 had older ages, higher baseline National Institutes of Health Stroke Scales scores, larger proportions of baseline Glasgow Coma Scale (GCS) score of 3-8 and grade of kobuta water swallow test ≥ 3, higher white blood cell (WBC) counts (all p values <0.05). The independent predictors for SAP with PaO2/FiO2 ratio ≤ 240 included ages (adjusted odds ratio [OR], 1.043; 95% confidential interval [CI], 1.011-1.077; p = 0.009), baseline GCS scores of 3-8 (adjusted OR, 2.802; 95% CI, 1.214-6.465; p = 0.016), and ln-transformed WBC counts after SAP diagnosis (adjusted OR, 3.977; 95% CI, 1.226-12.896; p = 0.021). SAP with PaO2/FiO2 ratio ≤ 240 was robustly associated with longer hospitalization days (adjusted OR, 1.074; 95% CI, 1.01-1.143; p = 0.024). SAP with PaO2/FiO2 ratio ≤ 240 is shown in significant relevance to the prolonged in-hospital stays among post-interventional patients. Older ages, baseline GCS scores of 3-8, and higher WBC counts after SAP diagnosis can independently predict the occurrence of SAP with a lower PaO2/FiO2 ratio. Further validation studies are needed.

Incidence, Clinical Features, and Outcome of AllTrans-Retinoic Acid Syndrome in 413 Cases of Newly Diagnosed Acute Promyelocytic Leukemia

A positive relation between the metabolic syndrome (MetS) and inflammatory activity has been reported. The purpose of this investigation was to study the relationships between 1) white blood cell (WBC) count and MetS, 2) WBC count and the individual components of MetS and 3) WBC count and insulin sensitivity in 75-year-old women and men from the general population. The study included 200 women and 196 men comprising 64% of the 75-year old people from the city of Västerås in Sweden. MetS was defined according to the National Cholesterol Education Program (NCEP). WBC count (10(9)/L; median and interquartile range) was 5.7 (4.9-6.8) for women and 6.3 (5.4-7.2) for men, P < .001 for gender difference. For women with and without MetS, WBC count was 6.3 (5.3-7.3) and 5.4(4.7-6.3), respectively. For men the corresponding figures were 6.7 (5.9-7.6) and 6.1 (5.4-7.1).The difference in WBC count between individuals with and without MetS was significant (P < .001 for women; P = .014 for men). All individual components of MetS (with exception of blood pressure) were more strongly associated with WBC count for women than for men. Insulin sensitivity, measured as HOMA-IR (HOmeostasis Model Assessment-Insulin Resistance) index, was significantly associated with WBC count in women but not in men. In this elderly population, individuals with MetS had a higher WBC count than those without. Women had a lower WBC count and stronger relationship between WBC count and insulin sensitivity than did men.

Simple SummaryAround 12–38% of acute promyelocytic leukemia (APL) patients carry the FLT3-ITD mutation, which has been associated with several poor-prognosis indicators such as high white blood cell counts, M3v variant morphology, and the bcr3 isoform. We aimed to retrospectively study the impact of FLT3-ITD mutations in APL patients in regard to clinical features, treatment courses, and outcomes. We demonstrate that Sanz high-risk status APL correlates with high FLT3-ITD allelic burdens, with every 1% increase in allelic burden correlating with a 0.6 × 109/L increase in white blood cell count (WBC). The presence of FLT3-ITD was associated with decreased remission rates and higher 5-year mortality from the time of diagnosis. These findings provide novel revelations regarding the features of FLT3-ITD APL, particularly in regard to allelic burden, that warrant further study.The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3-ITD. APL patients with FLT3-ITD had higher baseline white blood cell counts (WBCs) (p < 0.001), higher hemoglobin, (p = 0.03), higher aspartate aminotransferase (p = 0.001), lower platelets (p = 0.004), lower fibrinogen (p = 0.003), and higher incidences of disseminated intravascular coagulation (p = 0.005), M3v variant morphology (p < 0.001), and the bcr3 isoform (p < 0.001). FLT3-ITD was associated with inferior post-consolidation complete remission (CR) (p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3-WT (wild-type) (p = 0.02). FLT3-ITD was strongly associated with baseline WBCs ≥ 25 × 109/L (odds ratio (OR): 54.4; 95% CI: 10.4–286.1; p < 0.001). High FLT3-ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increase in allelic burden corresponding to a 0.6 × 109/L increase in WBC. HR APL was associated with a 38.5% increase in allelic burden compared with low-risk (LR) APL (95% CI: 19.8–57.2; p < 0.001). Our results provide additional evidence that FLT3-ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.

An elevated white blood cell (WBC) count and C-reactive protein (CRP) concentration are associated with acute myocardial infarction (AMI) and long-term mortality in patients with coronary artery disease. Their relationship with short-term prognosis following AMI is less clear, however. We investigated the relationship between WBC count and CRP concentration, obtained at the time of admission, and the development of subsequent ischaemic coronary events (SICE) within 30 days of AMI in 177 patients. After adjustment for confounding factors, CRP concentration was found to be a strong independent predictor for SICE within 30 days in patients with AMI. WBC count was not found to be an independent predictor, but there was a strong correlation between high WBC counts and the onset of SICE within 30 days in patients with AMI. We conclude that CRP concentration and WBC count could be used to predict the short-term prognosis of patients with AMI.

Early leakage detection following bariatric procedures is crucial, but a standardized evaluation method is lacking. The aim was to validate the potential benefits of postoperative day 1 (POD1) C-reactive protein (CRP) levels and white blood cell (WBC) counts in distinguishing at-risk patients following Roux-en-Y gastric bypass (RYGB) while considering the impact of obesity-related chronic inflammation. Retrospective analysis of 261 consecutive patients aged 18-65 years with a body mass index (BMI) of 32.5-50 kg/m2 who underwent primary RYGB between 2017 and 2022. Sequential changes in CRP levels and WBC counts measured 48 h preoperatively and on POD1 morning were collected and compared between patients with/without complications and in patients without complications stratified by preoperative CRP levels. Female patients and those with a higher BMI tended to have higher baseline CRP levels, which were positively related to postoperative CRP. Patients experiencing complications had higher WBC counts and a higher prevalence of WBC counts >14,000/μl (77.8% vs. 25.4%; p<0.001) than those without complications. Baseline CRP ≥ 0.3 mg/dl, a longer operative time, and blood loss >10 ml were significantly more common with WBC counts above 14,000/μl; a reasonable range of change in WBC count (∆WBC) derived from its positive correlation to postoperative WBC count (r=0.6695) may serve as a useful complementary indicator. An individualized CRP threshold setting and integrated interpretation of the WBC count can be more appropriate than using static criteria for differentiating at-risk patients after RYGB. Further studies are needed to validate these findings and determine their generalizability.

BackgroundSmoking has been linked to low-grade systemic inflammation, a known risk factor for disease. This state is reflected in elevated white blood cell (WBC) count.ObjectiveWe analyzed the relationship between WBC count and smoking in healthy men and women across several age ranges who underwent preventive medical check-ups in the workplace. We also analysed the relationship between smoking and lung function.MethodsCross-sectional descriptive study in 163 459 men and 59 382 women aged between 16 and 70 years. Data analysed were smoking status, WBC count, and spirometry readings.ResultsTotal WBC showed higher counts in both male and female smokers, around 1000 to 1300 cell/ml (t test, P < 0.001). Forced expiratory volume in 1 second (FEV1%) was higher in nonsmokers for both sexes between 25 to 54 years (t test, P < 0.001). Analysis of covariance showed a multiple variable effect of age, sex, smoking status, body mass index on WBC count. The relationship between WBC blood count and smoking status was confirmed after the sample was stratified for these variables. Smokers with airway obstruction measured by FEV1% were found to have higher WBC counts, in comparison to smokers with a normal FEV1% among similar age and BMI groups.ConclusionsSmoking increases WBC count and affects lung function. The effects are evident across a wide age range, underlining the importance of initiating preventive measures as soon as an individual begins to smoke.