Changes In Hematological Parameters Research Articles

Diagnostic significance of hematological parameters in brucellosis

<b>Introduction:</b> Changes in hematological parameters are frequently observed in brucellosis patients. In this study, it was aimed to evaluate the diagnostic significance of some hematological parameters in patients with brucellosis<b>.</b><br /> <b>Material and methods: </b>In this case-control study, the data of brucellosis patients and healthy volunteers followed up in the Outpatient Clinic of Infectious Diseases between 2018 and 2020 were retrospectively examined. In the hemogram examination of patients with brucellosis and health volunteers; hematological parameters such as the leukocyte, hemoglobin, neutrophil, lymphocyte, monocyte, platelet, ratio of neutrophil/lymphocyte, ratio of platelet/lymphocyte, ratio of monocyte/lymphocyte and mean platelet volume were compared.<br /> <b>Results: </b>255 people, 169 (66.3%) of whom were diagnosed with brucellosis and 86 (33.7%) from the control group, were included to the study. These participants of 112 (43.9%) were male and 143 (56.1%) were female. The patients diagnosed with brucellosis, of 62 (36.7%) were considered acute, of 62 (36.7%) subacute, and of 45 (26.6%) chronic brucellosis. leukocyte, hemoglobin, neutrophil, and neutrophil/lymphocyte levels were found to be lower in the brucellosis group compared to the control group, while mean platelet volume level was found to be higher. Hemoglobin was found to be lower and mean platelet volume higher in all brucellosis subgroups.<br /> <b>Conclusion: </b>In this study, the following findings were determined to be important: the lowness of leucocyte and hemoglobin and highness of mean platelet volume in brucellosis patients, as well as the highness of lymphocyte levels and lowness of neutrophil/lymphocyte and platelet/lymphocyte levels in the subacute brucellosis subgroup. In addition, it was concluded that the mean platelet volume parameter can be used as a diagnostic test for brucellosis.

Systemic Inflammatory Response as a Prognostic Factor in Breast Cancer. Part II. Hematological Markers of Inflammation

Chronic inflammation is one of the recognized factors contributing to the onset and progression of malignant neoplasms. At the systemic level, a chronic inflammatory process is accompanied by an increased levels of inflammatory mediators and a change in hematological parameters of peripheral blood. According to numerous clinical studies, the change in the ratio of blood cell populations in cancer patients is an independent prognostic factor in malignant tumors of various localizations. This review is devoted to hematological parameters of the systemic inflammatory response (SIR) in breast cancer (BC). The review presents the characteristics of blood cells used for calculations of hematological indices (neutrophils, lymphocytes, monocytes, platelets); approaches for assessing SIR using these indices (NLR, PLR, LMR, etc.); comparative analysis of data on the association of the hematological indices with the clinical and morphological features of BC, patient survival and tumor response to chemotherapy. The data indicating the benefit of SIR hematological markers investigation during monitoring after treatment are summarized. Complex algorithms, including clinical, morphological and hematological factors, which are proposed to improve the quality of prognosis assessment, are considered. The information accumulated to date suggests that hematological indices reflecting SIR activity in BC patients can serve as additional independent prognostic factors. The development of the prognostic algorithms that are informative for certain clinical groups of BC patients is a promising area of research.

Variation in hematological parameters due to tobacco cigarette smoking in healthy male individuals.

Objective: To evaluate the changes in hematological parameters in healthy male smokers. Study Design: Descriptive Cross - Sectional study. Setting: HITEC – IMS Taxila. Period: December 2021 to May 2022. Material & Methods: Hematological Parameters including complete blood counts (WBC, RBC, Hb, MCV, MCH, MCHC, HCT, RDW, PLT), Differential Leukocyte Count, ESR and PT, APTT were done in each case. The data were entered and analyzed on SPSS version 22. Results: Mean age of smokers was 28.72 ± 6.79 years while mean age of non-smokers was 30.63 ± 6.73 years. Duration of smoking was between 4 to 28 years and number of cigarettes was between 5 to 50 / day. Among hematological parameters; WBC count, Lymphocyte count, RBC count, hemoglobin, MCV, MCH and ESR were significantly raised; while neutrophil count was significantly low in smokers as compared to non-smokers. It was also observed that values of WBC count and prothrombin time were significantly higher in individuals with a smoking history of more than 10 years. Conclusion: In conclusion, smoking has adverse effects on the various hematological parameters that have been reported to be associated with a greater risk for developing hazardous effects on health. So, we suggest that physicians should evaluate their patients at every visit and strictly recommend them early cessation of smoking so that we could prevent our young generation from future ailments.

Inflammatory profile of apical periodontitis exacerbated by cigarette smoke inhalation: Histological and immunohistochemical analysis in rats.

The aim of this study was to evaluate the effects of cigarette smoke inhalation (CSI) on inflammation, pro-inflammatory mediators and haematological parameters in rats with induced apical periodontitis (AP). Thirty-two 3-month-old male Wistar rats were divided into four experimental groups (n=8): C-Control; S-rats with CSI; AP-rats with AP; and SAP-rats with CSI + AP. Animals in groups S and SAP inhaled cigarette smoke by remaining inside a smoking chamber for 8 min, three times daily, for 50 days. After 20 days of smoke inhalation, animals in AP and SAP groups had the pulps of the lower right first molar exposed to oral environment for 30 days to induce AP. In these subsequent 30 days, animals in group S and SAP continued with CSI. On Day 50, animals were euthanized and mandibles were histologically processed to assess inflammatory infiltrate, immunohistochemical interleukins (IL-1β, IL-6 and TNF-α), and blood samples collected for laboratory analysis. The Mann-Whitney test was performed for non-parametric data and the pairwise analyses of Student's t-test for parametric data, with a significance level of p < .050. Inflammatory infiltrate was moderate in AP group and more severe in the SAP (p=.010). The interleukins IL-6, IL-1β and TNF-α were higher in SAP group (p < .001) when compared to the AP group. A greater number of red blood cells (p=.010), haemoglobin (p=.007) and neutrophils (p=.014) were observed in the SAP group in comparison with the AP group. Cigarette smoke inhalation induced a more severe inflammatory infiltrate, with increased levels of pro-inflammatory cytokines and changes in haematological parameters in rats with induced AP. Thus, CSI aggravated AP, exacerbating the inflammatory response.

Radioligand therapy with &lt;sup&gt;177&lt;/sup&gt;Lu-DOTA-PSMA in metastatic castration-resistant prostate cancer. Pharmacokinetics, safety, antitumour efficacy

INTRODUCTION: The results of studies of clinical potential of a new domestic radiopharmaceutical 177Lu-DOTA-PSMA in patients with metastatic castration-resistant prostate cancer are presented in this article.OBJECTIVE: The pharmacokinetics, safety and tolerability of radiopharmaceutical were studied. Tolerability of increasing activities — 5.0, 7.5 and 10.0 GBq was investigated.MATERIALS AND METHODS: The study included 12 patients with metastatic castration-resistant prostate cancer, who progressed after previous treatment. The first 4 patients was treated by 5 GBq of 177Lu DOTA-PSMA, the next 4 patients of the second group was treated by 7.5 GBq, and the 4 patients of the third group was treated by 10 GBq. Radiopharmacokinetics was studied by whole-body scintigraphy, SPECT/CT, blood and urine radiometry. The radiation-absorbed dose (RAD) of metastases and organs at risk was studied by clinical dosimetry. Safety assessment also was studied by hematological status. All patients was taken a complete blood count, a biochemical blood test before course of therapy treatable and during the case study.RESULTS: Study data showed high accumulation of 177Lu-DOTA-PSMA the in pathological focus, the distribution in the body conformed to the previous data of PET/CT study. Blood radiometry showed that 177Lu-DOTA-PSMA rapidly excreted from the bloodstream (during the first hours after injection). Urine radiometry showed that, more than half of the injected dose was excreted during 2 days (from 34.4% to 88.8%).DISCUSSION: During the study was solicited increasing of pain syndrome, dry mouth. Most patients had moderate myelosuppression. Changes in hematological parameters had a transistor character, the adverse event resolved without consequences in 5 week. 4th grade of NCI CTCAE hematological toxicity criteria wasn’t identified. Serious adverse events weren’t identified too.CONCLUSIONS: Radiopharmaceutical demonstrated high affinity for tumor tissue and safety in the clinical use. Data, which demonstrating a high potential anti-tumor efficacy of radiopharmaceutical, were obtained. Dosimetric studies showed radiation safety of work with radiopharmaceutical for the personnel.

Haematological parameters and SARS-CoV-2 RT PCR positivity among patients at fever clinic in a tertiary care hospital in Bangladesh

The COVID-19 pandemic has had a consequential impact on the global health system. Multisystem involvement is common in COVID-19. Many COVID-19 patients also showed changes in haematological parameters. This cross-sectional study included patients who attended the fever clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, with fever and/or upper respiratory symptoms. Demographic information, information regarding symptoms, exposure and comorbidities were collected. Complete blood count profile and C-reactive protein were done. Patients underwent RT-PCR for Covid-19 at the fever clinic. A total of 350 patients were included in the study. The study revealed that 21.4% of respondents were COVID-19 positive. PCR-positive patients were more likely to be symptomatic and had elevated C reactive protein levels. COVID-19 positive patients also showed higher total leucocyte, neutrophil, lymphocyte, eosinophil, basophil, and platelet count. BSMMU J 2022; 15(2): 75-79

Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 after Oral Administration to Laboratory Animals.

Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments.

Plasma Volume Variations in Professional Soccer Players: Difference Between Pre- and Competitive Season

Background: Variations in plasma volume and hematological parameters occur before and after training in soccer players. However, there are no reports on changes in hematological parameters resulting from a half-season of training in professional soccer players. Objectives: To investigate the effects of training load on plasma volume variations in elite soccer players. Methods: Twenty soccer players from the 1st French division soccer league (Ligue 1) were included in the study. The training load was evaluated using the rating of perceived exertion (RPE, 10- Borg scale) after each training session and each match. Anthropometrics characteristics, hematocrit (Ht), hemoglobin (Hb) and plasma volume variations (PVV) were assessed at 3 different times: T1: Baseline (before the first week of pre-season), T2: At the end of pre-season (after 8 weeks of training) and T3: At the end of the first competitive period (after 26 weeks of training and at halfway of the competitive season). Results: Values of Ht and lean body mass (LBM) increased during the first competitive period from T1 to T3 (Ht: ∆↑8%, P = 0.037, effect sizes (ES) = 1.0; LBM: ∆↑4%, P = 0.041, ES = 0.83) and from T2 to T3 (LBM: (∆↑2%; P = 0.05; ES = 0.77). Moreover, PVV decreased from T2 to T3 (P = 0.002, ES = 0.5) and from T1 to T3 (P &lt; 0.05; ES = 1.26). There were no differences in Hb at T1, T2 or T3. Conclusions: Changes in body weights, PVV and Ht during preparatory and competitive phases were affected by the training load and competitive play.

Seasonal Changes in Hematological Parameters in House Sparrows of Subtropical Pakistan.

House sparrow is a globally adaptive bird. The way this creature adapted to all areas of the world, having different selection pressures, is interesting to understand. The present study is focused on seasonal changes, having different selection pressures and how it is adapted to these changes and whether hematological flexibility plays a role in this success. House sparrow's adaptations in the same area, during different seasons, have been studied in a sub-tropical area, Potohar, Pakistan. We used hematological parameter analysis for this purpose. Blood samples were collected from Sparrows in winter, spring, and summer and analyzed for some hematological parameters. White blood cells (WBCs) were higher in spring and summer which may relate to mating promiscuity. Sparrows were more stressed in summer. The Red blood cells (RBCs) and hematocrit (Hct) were greater in summer. Mean corpuscular volume (MCV) is lower in summer. This may have an adaptation to cope with high stress in summer as small-size RBCs increase gaseous exchange. Platelets were not affected by season or gender. Mean corpuscular volume and Mean corpuscular hemoglobin (MCH) are positively correlated with each other. Red blood cells, hemoglobin (Hb) and MCV were higher in males during the spring season perhaps as an adaptation to energetic activities during spring like mating calls and search for nesting sites. White blood cells remained the same in both genders in summer and winter, and effected in spring may be related to the mating system. Behavioral state is linked with physiological states that shows tradeoff and life history traits. This study is a small effort to know this incredible species. We can work further in different parts of the world to explore different aspects of it.

Efficacy of ferric carboxymaltose in iron deficiency anemia patients scheduled for pancreaticoduodenectomy.

Perioperative transfusion is reported to be an independent risk factor not only for postoperative complications but also for early recurrence of periampullary carcinoma after pancreaticoduodenectomy (PD). The purpose of this study was to evaluate the safety and efficacy of ferric carboxymaltose (FCM) in reducing the need for perioperative transfusion in iron deficiency anemia patients scheduled for PD. Twenty-two male patients (hemoglobin [Hb] 7 to <13 g/dL) and 18 female patients (Hb 7 to <12 g/dL) were enrolled in the study group and administered FCM 1-3 weeks before PD. The perioperative transfusion rate was the primary endpoint; morbidity, length of postoperative hospital stay, change in hematological parameters after FCM injection, and adverse effects of FCM were also investigated. The perioperative transfusion rate of the study group was 22.5% (9 of 40). Hb level was significantly higher on the day of the operation compared to baseline (P < 0.001). Levels of Hb, transferrin saturation, and ferritin were higher at the follow-up compared to baseline (P = 0.008, P = 0.033, and P < 0.001, respectively). FCM administration was associated with a reduced need for perioperative transfusion and can safely stabilize hematological parameters.

Impact of Malarial Infection on Hematological Parameters in Patients at Tertiary Care Hospitals in D.I. Khan

Malaria is among the leading parasitic infections in world causing major health problems. Plasmodium, being a blood parasite, causes changes in blood parameters. This study was aimed at identifying the Plasmodium specie and measuring the changes that occurred in hematological parameters, in malaria patients. The sample size consisted of 109 individuals divided into two (Infected and Control) groups: 71 malaria-positive and 38 malaria-negative individuals. The diagnosis was based on staining and direct visualization of the parasite under a microscope. Blood CP was performed on the "Sysmex XP 300 analyzer". Non-normally distributed continuous variables were compared using the Mann-Whitney U test. An association between malaria and thrombocytopenia and anemia was noted but severe cases were not observed. Female patients were more Anaemic and the reduction in leukocyte count was also observed among malaria patients. Malaria causes changes in hematological parameters with thrombocytopenia during malarial infection. However, anemia was observed in female patients.

Evaluation of erythrocyte arginase activity, plasma nitric oxide concentration and oxidative stress status in cattle with anaplasmosis

Bovine anaplasmosis is an arthropod-borne disease characterized by high fever, anaemia and sometimes jaundice. The role of oxidative stress in anaplasmosis has been investigated, but erythrocyte arginase (ARG) activity has not been studied. In this study, we aimed to investigate the changes in haematological parameters, erythrocyte ARG activity, plasma nitric oxide (NO) levels and oxidative stress parameters and explain the relationship between each other in cattle with anaplasmosis. The material of this study consisted of 14 cattle, aged 10–12 months with anaplasmosis (infected group) and 14 healthy cattle aged 10–12 months (control group). Our data revealed that leukocyte parameters and plasma NO levels and serum malondialdehyde (MDA), total oxidant status (TOS) and oxidative stress index (OSI) levels were higher while erythrocyte parameters, erythrocyte ARG activity and serum total antioxidant status (TAS) and glutathione (GSH) levels were lower in the infected group compared to the control group. There was a strong correlation between erythrocyte ARG activity and NO, MDA, TOS, OSI, TAS and GSH. ROC analysis and correlation results suggest that erythrocyte ARG activity is an effective oxidative stress marker. We concluded that severe oxidative stress occurs in anaplasmosis. As the severity of anaemia increases, erythrocyte ARG activity plummets while plasma NO level elevates. These two parameters may also be used as prognostic and oxidative stress markers. Although decreased erythrocyte ARG activity is a disadvantage in haemolytic diseases, this situation can be compensated by increased NO. Thus, homeostasis of these two parameters may contribute to the elimination of the infection.

Experimental Ascaridiasis Induced Changes in Haematological Parameters in WLH Chicks

The Species Ascaridia galli is a common and serious helminth parasite of poultry. Present studywas conducted to determine its effects on the poultry. The impact of experimental ascaridiasiswas studied on WLH chicks in terms of blood parameters. The result obtained is analyzedstatistically and are presented here.

The long-term efficacy in blood transfusions, hematologic parameter changes, and complications after splenectomy in patients with transfusion-dependent thalassemia

BackgroundA splenectomy can reduce transfusion requirements in patients with thalassemia. However, the role of a splenectomy remains controversial because its efficacy has not yet been fully determined and there are concerns over potential complications. The purpose of this study was to assess the efficacy, potential changes in hematologic parameters, and any complications associated with splenectomy. MethodsMedical records of 50 patients with transfusion-dependent thalassemia (TDT) who had undergone a splenectomy, along with those of 20 control subjects with intact spleens, were retrospectively reviewed. ResultsThe primary outcomes indicate the efficacy of a splenectomy in reducing red cell transfusions. Fifty TDT post-splenectomy patients were included in this study, of which 28 (56%) were female. The median age of all patients was 20.5 (18–28 years of age). Twenty-seven patients (54%) transformed from TDT to non-transfusion-dependent thalassemia (NTDT) after the splenectomy; 100% with Hb H disease, 58.3% with beta-thalassemia/Hb E disease, and 23.5% with homozygous beta-thalassemia. According to multivariable logistic regression analysis, Hb H disease (adjusted OR 55.23, 95% CI 1.35–22.8.10) and receiving a splenectomy at > ten years of age (adjusted OR 25.36, 95% CI 1.62–396.47) were associated with higher responses. The prevalence of pulmonary hypertension and thromboembolic events were similar between the splenectomy patients and non-splenectomy patients. ConclusionSplenectomy reduced transfusion requirements in TDT patients. The predictive factors as a response to a splenectomy included Hb H disease amongthose receiving a splenectomy at > ten years of age.

STUDY OF HEMATOLOGICAL PARAMETERS IN PATIENTS WITH COVID-19 DISEASE IN KURDISTAN REGION-IRAQ

&nbsp; Background: Coronavirus disease 2019 is an infectious disease that was found at the end of 2019. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recognized as the virus that leads to COVID-19. The study was directed to find out the hematological parameter changes in COVID-19 patients according to the severity of the disease. Methods: The study has been done in two centers Sulaymaniyah and Duhok Governorates for a period of six months between September 2021 to March 2022. A total of 201 enrolled patients were included. For each patient demographic characteristics and blood test results (total and differential WBC, Hb, platelet, ferritin, CRP, D-dimer, NLR, PLR) were collected, following the severity of the disease and the outcome of each one of the patients. SPSS software was used for statistical analysis. Results: The study revealed that female patients were more than males 60.2% and 39.8% respectively with an overall mean age of 54.65±17 years. The mean duration of hospitalization is 14.4 ± 7.7 days. Furthermore, the study showed that patients had 30.8% leukocytosis,17.4% lymphopenia, and 31.8% neutrophilia. Higher NLR and PLT are seen in severe cases with NLR ≥3.1and PLR ≥ 285. Also, high levels of CRP, D-dimer, and ferritin were seen in severe COVID-19 patients. Conclusions: Changes in hematological parameters can be useful in predicting of the disease severity of COVID-19 patients.

Bromelain Modulates Liver Injury, Hematological, Molecular, and Biochemical Perturbations Induced by Aluminum via Oxidative Stress Inhibition.

Aluminum (Al) is an important factor in the environment as it is used in agriculture and several industries leading to hazardous effects via oxidative stress. Bromelain is a cheap extract from the byproduct waste of Ananas comosus stem. It has been used in several biological and therapeutic applications. So, this study was undertaken to assess the hepatoprotective potential of bromelain versus oxidative stress induced by aluminum chloride in rats. Results revealed that administration of AlCl3 reduced the body and liver weights and increased Al concentration in the blood and liver tissue. Also, AlCl3 caused valuable changes in hematological parameters and increased TBARS and H2O2 concentrations in rat liver. Enzymatic (SOD, CAT, GPx, GR, and GST) and nonenzymatic (GSH) antioxidants and protein content were significantly decreased. Furthermore, alterations in liver biomarkers such as bilirubin level and enzyme activities in both serum and liver homogenate (LDH, ALP, AST, and ALT) were detected. AlCl3 also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1β)], tumor necrosis factor-alpha (TNF-α), as well as matrix metalloproteinase (MMP9), and downregulation of nuclear factor erythroid 2 (Nrf2) expression. In addition, histopathological examination showed significant variations in the liver that confirms the biochemical results. Otherwise, bromelain intake alone slumped lipid peroxidation and gotten better antioxidant status significantly. Moreover, supplementation with bromelain before AlCl3 intoxication restores enzymatic and nonenzymatic antioxidants as well as biochemical indices and tissue architecture with respect to the AlCl3 group. In conclusion, bromelain proved its remarkable protective power to abolish AlCl3 toxicity. So, it might represent a new strategy in the therapy of metal toxicity by its antioxidant capacity.

Disease Progression and Leukemic Transformation in Patients With Lower-Risk Myelofibrosis (MF): An Analysis from MOST

Background: Progressive disease (PD) in MF is associated with increased bone marrow fibrosis, worsening anemia, and an increase in circulating blasts and can result in leukemic transformation (LT). LT is a rare (~11% incidence) but fatal complication of MF with a mortality rate of 97% and a median survival of 3.6 months. Real-world data regarding PD and LT in lower-risk MF are limited. This analysis from the Myelofibrosis and Essential Thrombocythemia Observational Study (MOST; NCT02953704) describes the incidence of PD, including LT, in patients with lower-risk MF and compares the baseline characteristics of patients who progressed vs those who did not. Methods: MOST is a longitudinal, noninterventional, prospective, observational study of patients with clinical diagnoses of MF or essential thrombocythemia enrolled at clinical practices in the US. Patients included in this analysis (≥18 years) had low-risk or intermediate-1 (INT-1)-risk MF (by age >65 years alone) stratified by the Dynamic International Prognostic Scoring System (Blood. 2010;115:1703) at enrollment and were followed for at least 3 years. Baseline data were collected as previously described (Gerds A. Clin Lymphoma Myeloma Leuk. 2022;22:e532-e540). PD was defined as physician-reported PD, LT, and/or death by reason of progression. Results: Of the 232 patients with MF enrolled in MOST, 204 patients (low-risk: n=84, 41.2%; INT-1-risk: n=120, 58.8%) were included in this analysis (data cutoff: July 5, 2022). The median (range) time from MF diagnosis to enrollment was 1.8 (0-38) years and the median (range) enrollment duration was 4.2 (3.3-5.4) years. Of 193 patients with available data on disease progression, 46 patients (23.8%) had physician-reported PD; of these, 18 (22.0%) were low-risk and 28 (25.2%) were INT-1-risk. The most commonly reported indicator was change in hematologic parameters (n=27 [58.7%]), followed by change in spleen size (n=19 [41.3%]), MF-related symptoms (n=16 [34.8%]), and blast counts (n=8 [17.4%]). LT was reported in 15 patients (7.8%); of these 4 (4.9%) were low-risk and 11 (9.9%) were INT-1-risk. Death by any cause was reported in 30 patients (14.7%; PD, n=16, without PD, n=9; unknown PD, n=5). Patient baseline characteristics are shown in Table 1. Patients who had PD were older than patients without (median [range] age: PD, 70.0 [35-88] vs without PD, 66.5 [35-88] years). Bone marrow biopsy/aspiration and mutation tests at diagnosis were reported in 98.3% and 80.7% of patients with PD and in 91.8% and 82.8% of patients without PD, respectively. Significant differences in the symptomatology of patients with PD vs without PD were not detected at time of enrollment. More than half of patients with PD and without PD were receiving MF-directed monotherapy at enrollment (59.3% vs 55.2%). The most common monotherapies received in patients with PD vs without PD were hydroxyurea (15.3% vs 28.4%) and ruxolitinib (37.3% vs 17.9%). Six patients (PD, n=3; without PD, n=3) received >1 MF-directed therapy. Conclusion: This real-world analysis of data from patients enrolled in MOST describes the disease evolution of patients with lower-risk MF. After ~3 years of follow-up, a relatively high proportion of patients in this population had physician-reported PD or LT (23.8% and 7.8%, respectively). Baseline characteristics and symptoms did not differ between those who progressed and those who did not; however, further analysis of molecular and post-baseline data may provide insight into risk factors for disease progression in this lower-risk population. Identification of patients with higher risk of PD is likely to improve disease management and outcomes for patients with lower-risk MF. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Phase Ⅱ,Open-Label, Multicenter, Single-Arm Study Investigating the Efficacy and Safety of Ropeginterferon Alfa-2b in Chinese Patients with Polycythemia Vera Resistant or Intolerant to Hydroxyurea(HU)

Background: Polycythemia vera (PV) is a common type of BCR-ABL-negative myeloproliferative neoplasms. It often harbors a Janus kinase 2 (JAK2) gene mutation and is associated with elevated blood cell counts, symptoms that can be debilitating over time and risks of thrombosis and hemorrhage, and disease progression to myelofibrosis and acute myeloid leukemia. Ropeginterferon alfa-2b, a novel, site-selective, mono-pegylated proline-interferon alfa-2b, has improved pharmacokinetic properties, allowing dosing every 2 to 4 weeks, with improved tolerability and convenience. The safety and efficacy of ropeginterferon alfa-2b for the treatment of PV has been demonstrated in clinical studies conducted in Europe (PEGINVERA, PROUD-PV, CONTINUATION-PV) and Japan. The approved dosing scheme of ropeginterferon alfa-2b is 100 μg (or 50 μg in patients under another cytoreductive therapy) as a starting dose, with dose increment of 50 μg to the maximum recommended dose of 500 μg. Faster dose escalation may help patients achieve control of hematologic parameters quicker. Aims: The aim of this phase Ⅱ, single-arm study (A20-202) was to assess the safety and efficacy of ropeginterferon alfa-2b in Chinese PV patients utilizing an accelerated dose titration schedule. Methods: Chinese patients 18 years or older with a PV diagnosis according to World Health Organization 2016 criteria and were resistant or intolerant to hydroxyurea (HU) were enrolled. Ropeginterferon alfa-2b was administered subcutaneously every 2 weeks for 52 Weeks at a starting dose of 250 μg, followed by 350 µg at Week 2, and a target dose of 500 μg at Week 4. Patients received the target dose, if tolerated, for the remainder of the 52-week treatment. The primary endpoint was the proportion of patients who reach a complete hematologic response (CHR) at Week 24 (CHR: hematocrit <45% without phlebotomy or erythrocyte apheresis in the preceding 12 weeks, platelet≤400×109/L, leukocyte <10×109/L). Secondary endpoints included changes in hematologic parameters and JAK2V617F allele burden, time to first complete hematologic response, and duration of response. Safety endpoints included the incidence of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Results: As of the data cut-off date of 01 July 2022, a-total of 49 patients, 31 males and 18 females, with a median age of 56 years, were enrolled in this study. Mean baseline values were hematocrit 45.95%, leukocyte count 11.35×109/L, and platelet count 478.5×109/L. All patients had the JAK2V617F mutation (mean allele burden: 58.49%). One patient withdrew consent and discontinued the study. The data of 27 patients were available to evaluate the CHR at Week 24. Fourteen out of the 27 (51.85%) patients achieved a CHR at Week 24 of the treatment. This was comparable to the CHR rate of 43.1% at Week 52 observed in the PROUD-PV study. Hematocrit, leukocyte and platelet levels decreased over time with mean change ± SD from baseline to Week 24: -3.63± 6.14%, -5.77± 12.22×109/L, and -254.0± 177.23×109/L, respectively. JAK2V617F allele burden decreased over time with mean change ± SD from baseline to week 24: -13.95±16.74% (n=26); consistent with an increase in molecular response. The JAK2V617F allele burden in two patients became undetectable after the treatment, as measured by Next-Generation Sequencing with a lower limit of quantitation at 3% by the central laboratory. TEAEs occurred in 47 patients (95.9%). Grade≥3 AEs occurred in 8 of the patients (16.3%) and among them, possibly treatment-related Grade ≥ 3 AEs occurred in five patients (10.2%). Serious adverse events (SAE) occurred in 4 of the patients (8.2%), and possibly treatment-related SAE occurred in two patients (4.1%). The most common TEAEs were alanine aminotransferase increase (38.8%), leukopenia (36.7%) and aspartate aminotransferase increase (36.7%). Preliminary result did not show significant AESIs (e.g., cardiovascular and psychiatric events) in all the patients who received the treatment. Summary/Conclusion: The interim results of our study demonstrate that Ropeginterferon alfa-2b using a 250-350-500 μg dosing scheme was safe, well tolerated, and efficacious in Chinese patients with PV. The data suggest that using an accelerated dosing scheme helps patients achieve a CHR earlier.

Acute and sub-acute oral toxicity of the methanol extract of Adansonia digitata fruit pulp.

Most rural and urban-based communities in Africa rely on traditional remedies for their primary healthcare. One probable reason for this is the assumption that they are free of harmful side effects and toxicity, compared to orthodox drugs. However, very few plants have been thoroughly evaluated for their toxic effects. Adansonia digitata (A. digitata) also known as (Baobab) is a member of the Malvaceae family. Almost all components of the tree are utilized in traditional African medicine. The present study evaluated the potential toxicity of methanol extract from the fruit pulp of Adansonia digitata through acute and sub-acute oral administration in rats. The acute oral toxicity study was done according to Organization of Economic Co-operation and Development (OECD) guidelines no 425 using a limit dose of 2000 mg/kg body weight (BW). Sub-acute oral toxicity using (250, 500, and, 1000 mg/kg BW) was performed by daily administration for 28 days according to the OECD guideline 407. The acute toxicity study revealed no lethal effects and behavioral signs of toxicity at the tested dose indicating that LD is greater than 2000mg/kg. In the sub-acute study, no significant difference was observed in the body weight, organ weight, liver, and kidney parameters in all treated groups compared to the control. A non-significant decrease in packed cell volume (PCV) was observed across the groups. Also, a significant increase in the white blood cell count and a decrease in the lymphocyte count occurred in the group treated with 250 mg/kg BW. These results show that methanol extract of Adansonia digitata fruit pulp is generally safe on short-term use but can cause changes in haematological parameters on long-term use.

Rker-050, a Novel Activin Receptor Type II Ligand Trap, Rescued Anemia and Reduced Bone Loss in a Mouse Model of Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell diseases characterized by ineffective hematopoiesis, peripheral blood cytopenias and dysplasias resulting from molecular defects and dysregulated signaling that govern the regulation of hematopoietic stem and progenitor cells (HSPCs). Crosstalk between cells in the osteo-hematopoietic (O-H) niche are necessary for the maintenance and self-renewal of HSPCs. Additionally, MDS patients commonly present with osteopenia and osteoporosis further demonstrating the critical interplay between the O-H cells in the bone marrow (BM). Alterations in the interaction between bone precursors and HSPCs within the BM microenvironment have been linked to the pathophysiology of MDS. Transforming growth factor-beta (TGF-β) superfamily signaling is instrumental in regulating both normal hematopoiesis and bone homeostasis. KER-050 is a modified investigational activin receptor type II ligand trap designed to bind and inhibit select TGF-β superfamily ligands, including activin A, activin B, GDF8 and GDF11, to promote hematopoiesis and bone growth. Preclinical studies have demonstrated that treatment with a research form of KER-050 (RKER-050) increased bone mass and multi-lineage hematopoiesis in healthy mice. To further investigate the effect of RKER-050 on hematopoietic and bone systems within the MDS disease setting, the NUP98/HOX13 MDS mouse model was utilized. Five-month-old male MDS mice were treated with vehicle (VEH, n=10), or RKER-050 (050, 7.5mg/kg, n=9) once weekly for 6 weeks along with a wildtype vehicle (WT, n=7) control group. To assess changes in hematological parameters, CBCs were measured, bone marrow (BM) and splenocytes were characterized via flow cytometry. To investigate alterations of bone microarchitecture, femurs were assessed using microCT imaging. MDS-VEH mice showed a reduction in red blood cells (RBC; 30%), hemoglobin (HGB; 19%), hematocrit (HCT; 13%) and reticulocytes (Retic; 16%) compared to WT; all hallmarks of human MDS. Relative to MDS-VEH, MDS-050 showed increased RBC, HGB, HCT and Retic by 25%, 13%, 10% and 39%, respectively. The erythroid Ter119 positive (Ter119+) cell population was slightly reduced in BM and spleen of MDS-VEH mice compared to WT. The BM Ter119+ cells were unchanged in the MDS-050 cohort relative to MDS-VEH; however, the spleen Ter119+ cells were increased similar to the levels in WT mice. Specific erythroid precursor populations were increased in BM and spleen of MDS-VEH mice versus WT, consistent with the ineffective erythropoiesis in this model. Interestingly, erythroid precursor populations were similar between MDS-VEH and MDS-050, yet MDS-050 exhibited recovered RBC production, suggesting an increase in maturation of erythroid precursors with RKER-050 treatment. Given the importance of the O-H niche in regulating hematopoiesis along with osteoporosis and osteopenia being comorbidities of MDS, bone microarchitecture was also analyzed. In the distal femoral trabecular bone, relative to WT mice, MDS-VEH mice had significant increases in trabecular (Tb) separation (33%) and decreases in Tb number (28%), changes that are consistent with reduced bone strength. Bone volume (34%) and bone volume fraction (26%) decreased but were not statistically significant. MDS-050 treated mice had a significant increase in bone volume (71%), higher bone volume fraction (88%), increased Tb number (44%) and decreased Tb spacing (20%) compared to the MDS-VEH, supporting RKER-050's role in improving bone mass. Taken together, these results suggest that RKER-050 can mitigate anemia and bone loss in an MDS mouse model, potentially by rebalancing hematopoiesis and bone turnover. In particular, the ability of RKER-050 to improve bone microarchitecture within the trabecular region, where the O-H niche resides, could be an important step in reestablishing healthy blood cell production. Furthermore, exploratory PD data from an ongoing phase 2 clinical trial demonstrate improved blood parameters with KER-050 treatment, including platelet and RBC in MDS patients (Tan et al. 2022 EHA #P776), and changes in bone biomarkers are currently being evaluated in the study. KER-050, thus, represents a potentially promising approach for patients with MDS and other hematological diseases, including myelofibrosis, where ineffective hematopoiesis and defects in bone homeostasis occur.