scholarly journals Haemopoietic Potential of Tannin Fractionates of Vitex doniana Leaf on Nitrosobis (2-Oxopropyl) Amine Comobidity in Docetaxel-Induced Myelosuppression in Wistar Rat

Author(s):  
Godson Emeka Anyanwu ◽  
Ifeanacho Ezeteonu Abireh

Aim: This study investigated the haemopoietic potential of tannin fractionate of Vitex doniana leaf against nitosobis (2-oxopropyl) amine comorbidity in docetaxel-induced bone marrow suppression. Study Design: This is an experimental research. Place of Research: University of Nigeria, Enugu campus. Methodology: The male Wistar rats used in this experiment were twenty-eight in number, and they were grouped into 7, with each group having four rats. Group 1 served as control, and received 1ml of normal saline, while groups 2-7 were treated with Nitrosobis (2-oxopropyl) amine 5 mg/kg daily for 2 weeks. Then groups 3-7 were treated with 8 mg/Kg of docetaxel weekly for 2 weeks. And groups 4, 5 and 6 also received 250 mg/Kg and 500 mg/Kg and 1000 mg/kg of tannin, respectively, daily for 2 weeks. Group 7 received 40 mg/Kg of fesolate daily for 2 weeks. Results: The haemoglobin concentration and white blood cell count of rats in the groups treated with Nitrosobis (2-oxopropyl) amine alone (group 2) and Nitrosobis (2-oxopropyl) amine plus Docetaxel (group 3) showed statistically significant reduction (p=.05) in number when compared with the group treated with normal saline (group 1). The haemoglobin concentration and white blood cell count of the rats in the groups treated with 250 mg/kg, 500 mg/kg, and 1000 mg/kg of the tannin fractionate, in addition to the Nitrosobis (2-oxopropyl) amine and Docetxel (i.e. groups 4, 5, and 6, respectively) showed statistically significant dose dependent increase in number, with the group treated with 1000mg/kg showing the highest increment (p=.05). The cells in the bone marrow show significant reduction in number in the rats treated with Nitrosobis (2-oxopropyl) amine (group 2) and Nitrosobis (2-oxopropyl) amine plus docetaxel (group 3) when compared with the rats in group 1 (treated with normal saline). With the addition of graded doses of the tannin fractionate, 250 mg/kg, 500 mg/kg, and 1000mg/kg (i.e. groups 4, 5, and 6, respectively), the number of cells in the bone marrow showed statistically significant increase when compared to group 3 (treated with Nitrosobis (2-oxopropyl) amine plus docetxel), with the rats in the group treated with 1000 mg/kg of tannin fractionate (group 6) having the highest increment (p=.05). Conclusion: Tannin obtained from Vitex doniana leaf extract increases the haemoglobin concentration in dose dependent manner. It also increases the white blood cell count, and number of proliferating bone marrow cells, following suppression by Nitrosobis (2-oxopropyl) amine and Docetaxel. So, this tannin obtained from Vitex doniana leaf extract may be useful in clinical practice to cushion the myelosupression, anaemia and leukopenia that are associated with use of docetaxel in treatment of malignancies.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2273-2273
Author(s):  
Koji Sasaki ◽  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Jorge E. Cortes ◽  
Guillermo Garcia-Manero ◽  
...  

Abstract Background: Therapy-related myeloid neoplasms develop after cytotoxic chemotherapy or radiation therapy. The available data on the outcome of pts with t-de novo AML without antecedent history of myelodysplastic syndrome (MDS) is limited. Methods: We reviewed the records of pts with newly diagnosed AML who presented to our tertiary care center from 1/2000 to 1/2014. t-de novo AML was defined as having at least 20% blasts in bone marrow with a history of any previous cytotoxic chemotherapy or radiation therapy, and without an antecedent history of MDS. Leukemia-free survival (LFS) was defined as time from achieving complete response (CR) to relapse or death. The overall survival (OS) and LFS in pts with t-de novo AML were compared to those of with de novo AML with normal karyotype (NK) and complex karyotype (CK). Results: Among 1677 pts with newly diagnosed AML, 383 had de novo NK-AML, 218 had de novo CK-AML, and 187 had t-de novo AML. The median follow-up was 9.3 months (range; 0.2-161.0). Pt characteristics and outcomes are described in Table 1. Among the 187 pts, 69 had a history of lymphoma; 63 pts breast cancer (Ca); 10 pts colon Ca; 10 pts sarcoma; 8 pts prostate; 7 pts bladder Ca; 6 pts uterine Ca; 5 pts lung Ca; 5 pts head and neck Ca; 30 pts other type of Ca. Among the pts with t-de novo AML, 15 pts (8%) had a favorable-risk karyotype by WHO, 53 pts (28%) intermediate-risk karyotype, and 119 pts (64%) poor-risk karyotype. The median LFS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% confidence interval [CI]; 5.1-8.7), 19 months (95% CI; 13.0-25.2), and 6 months (95% CI; 9.0-13.5) (p<.001), respectively. The median OS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% CI; 5.9-8.9), 21 months (95% CI; 16.2-25.5), and 12 months (95%CI; 10.6-13.5) (p<.001), respectively. The results of univariate (UVA) and multivariate analysis (MVA) associated with OS were summarize in Table 1. MVA identified age over 60, white blood cell count (WBC) over 10 x103/µL, thrombocytopenia below 30 x103/µL, non-favorable cytogenetic abnormalities, positive RAS mutation, and the absence of CR or CR with incomplete platelet recovery (CRp) as poor prognostic features related to OS. Conclusion: LFS and OS were shorter in patients with t-de novo AML than in those with NK-AML but did not differ significantly from patients with CK-AML. Abstract 2273. Table 1. Patient Characteristics and Outcomes t-de novo AML [n= 187] de novo AML with NK [n= 383] de novo AML with CK [n= 218] P Age at diagnosis, median (years) 64 (21-89] 63 (17-90) 67 (18-87) Prior radiation therapy, No. (%) 101 (54) 0 0 Prior chemotherapy, No. (%) 186 (99) 0 0 White blood cell count at diagnosis, median (x103/µL) 3.2 (0.2-191) 4.3 (0.2-390.0) 2.9 (0.5-278.2) Hemoglobin at diagnosis, median (g/dL) 9.1 (4.5-12.9) 9.1 (4-14.6) 9.0 (2.5-14.2) Platelet count at diagnosis, median (x103/µL) 34 (4-454) 51 (3-469) 42 (2-319) LDH at diagnosis, median (IU/L) 1359 (210-22090) 1189 (200-42000) 1274 (231-20572) Peripheral blood blast percent at diagnosis, median (%) 8 (0-98) 9.5 (0-98) 10 (0-98) Bone marrow blast percent at diagnosis, median (%) 41 (0-96) 44 (0-96) 33 (0-97) Molecular genetic abnormalities at diagnosis, No. (%) FLT3-ITD 17 (9) 96 (25) 5 (2) FLT3-D835 6 (3) 23 (6) 1 (1) NPM1 7 (4) 104 (27) 4 (2) JAK2 3 (2) 6 (2) 8 (4) RAS 17 (9) 50 (13) 8 (4) RUNX1-RUNX1T1 4 (2) 0 0 CBFb-MYH 6 (3) 0 0 Response, No. (%) <0.001 Complete response 89 (48) 237 (62) 76 (35) Complete response without platelet recovery 15 (8) 1 (0) 15 (7) 1-year LFS, (%) 33 60 27 <0.001 2-year LFS, (%) 33 52 20 <0.001 1-year OS, (%) 34 68 30 <0.001 2-year OS, (%) 24 46 13 <0.001 UVA and MVA of OS in t-de novo AML UVA MVA Hazard ratio 95% CI Age at diagnosis Age =< 60 years - Age >60 years < .001 .001 2.238 1.417-3.534 White blood cell count (WBC) (x103/µL) WBC =< 10.0 - WBC > 10.0 .002 .037 1.617 1.030-2.540 Hemoglobin (Hgb) (g/dL) Hgb >= 8 - Hgb < 8 .749 Platelet count (Plt) (x103/µL) Plt >= 30 - Plt < 30 .008 .004 1.852 1.224-2.803 LDH (IU/L) LDH =<1000 - LDH > 1000 .640 Peripheral blood blast percent (PB blast)(%) PB blast =< 10% - PB blast >10% .178 Bone marrow blast percent (BM blast) (%) BM blast =<40% - BM blast >40% .393 Cytogenetic abnormality Favorable - Non-Favorable .002 .019 5.836 1.342-25.370 FLT3-ITD Negative - Positive .768 RAS Negative - Positive .047 .003 2.576 1.367-4.856 Response CR or CRp - Non-CR or CRp <.001 .009 .331 0.145-0.757 CR - Non-CR <.001 0.903 .950 0.418-2.160 Figure 1. LFS and OS Figure 1. LFS and OS Disclosures Kantarjian: ARIAD, Pfizer, Amgen: Research Funding.


2013 ◽  
Author(s):  
Μαρία Καπαρού

Introduction: Acute lymphoblastic leukemia (ALL) accounts for nearly 1/3 of all pediatric malignancies and 75% of all childhood leukemias. The annual incidence of ALL has been estimated to 30 cases per million, with a peak incidence in children aged two to five years. Progress in the diagnosis with novel molecular techniques, risk classification, and treatment strategy in ALL has led to cure rates that now exceed 80%. However, a significant proportion (20%) of patients fails to respond to therapy, and treatment failure can occur even in patients with favorable prognostic features. It has been suggested that leukemia is characterized by impaired balance between proliferation of blood cells and their capacity to undergo apoptosis. The aim of this study was to assess the expression of the apoptosis-related genes bcl-2 and bax in childhood ALL, both at the time of diagnosis and at remission achieved post induction treatment. In addition, we measured the levels of the apoptotic receptors Fas, FasLigand, and their co-expression on patients’ leukemic cells. To explore the prognostic significance of apoptosis-related genes in childhood ALL, we examined associations between expression levels and established clinical and cytogenetic disease parameters.Materials-Methods: The study included 26 children (eighteen boys, eight girls) with newly diagnosed ALL (twenty-three B-ALL, three T-ALL). The mean age was 7.1 ± 1.2 years, the mean white blood cell count was 27.5 ± 10.6 K/μL and the mean hemoglobin was 9.1 ± 0.6 g/dL. All patients were diagnosed, treated and followed at the Department of Pediatric Hematology-Oncology, University Hospital of Heraklion - Crete, and they received chemotherapy according to the ALL BFM 2000 protocol. There were 34 age-matched children who served as controls (20 children with benign blood diseases -12 with Idiopathic Thrombocytopenic Purpura, 8 with Autoimmune Neutropenias- and 14 children with solid tumors without bone marrow infiltration). Bone marrow specimens were obtained from all children, under informed consent signed by the parents/guardians. Cytogenetic abnormalities were examined with conventional karyotype and FISH. Disease remission following induction therapy was assessed by bone marrow microscopic evaluation and flow cytometry. Measurement of bcl-2 and bax mRNA was performed by quantitative real-time PCR, and membrane expression of Fas and Fas-L was assessed by flow cytometry in bone marrow mononuclear cells, both at diagnosis and at remission following induction chemotherapy.Results: At diagnosis, increased level of the apoptotic bax/bcl-2 ratio was observed in children older than 10 years and with higher white blood cell count. DNA index <1,16 was associated with increased bax/bcl-2 both at diagnosis and at remission, and the del(9p) abnormality with increased bax/bcl-2 at remission. Expression of the apoptotic receptor Fas was significantly higher at remission compared to diagnosis, which might reflect enhanced sensitivity of the leukemic clone to apoptosis and response to treatment. Conclusions: In conclusion, our study highlights the association between the apoptotic bax/bcl-2 ratio with high-risk features in children with ALL, such as older age, white blood cell count, the del(9p) abnormality and DNA index <1.16. The increase in Fas expression once remission has been achieved after induction treatment, could represent a prognostic factor of favorable response to chemotherapy and deserves further investigation. Delineation of the role of apoptosis in pathogenesis and prognosis of pediatric ALL should enable the design of novel targeted therapies.


2021 ◽  
Vol 11 (3) ◽  
pp. 195
Author(s):  
Yitang Sun ◽  
Jingqi Zhou ◽  
Kaixiong Ye

Increasing evidence shows that white blood cells are associated with the risk of coronavirus disease 2019 (COVID-19), but the direction and causality of this association are not clear. To evaluate the causal associations between various white blood cell traits and the COVID-19 susceptibility and severity, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses with summary statistics from the largest and most recent genome-wide association studies. Our MR results indicated causal protective effects of higher basophil count, basophil percentage of white blood cells, and myeloid white blood cell count on severe COVID-19, with odds ratios (OR) per standard deviation increment of 0.75 (95% CI: 0.60–0.95), 0.70 (95% CI: 0.54–0.92), and 0.85 (95% CI: 0.73–0.98), respectively. Neither COVID-19 severity nor susceptibility was associated with white blood cell traits in our reverse MR results. Genetically predicted high basophil count, basophil percentage of white blood cells, and myeloid white blood cell count are associated with a lower risk of developing severe COVID-19. Individuals with a lower genetic capacity for basophils are likely at risk, while enhancing the production of basophils may be an effective therapeutic strategy.


2021 ◽  
pp. 247553032110007
Author(s):  
Eric Munger ◽  
Amit K. Dey ◽  
Justin Rodante ◽  
Martin P. Playford ◽  
Alexander V. Sorokin ◽  
...  

Background: Psoriasis is associated with accelerated non-calcified coronary plaque burden (NCB) by coronary computed tomography angiography (CCTA). Machine learning (ML) algorithms have been shown to effectively identify cardiometabolic variables with NCB in cross-sectional analysis. Objective: To use ML methods to characterize important predictors of change in NCB by CCTA in psoriasis over 1-year of observation. Methods: The analysis included 182 consecutive patients with 80 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative, a prospective, observational cohort study at baseline and 1-year using the random forest regression algorithm. NCB was assessed at baseline and 1-year from CCTA. Results: Using ML, we identified variables of high importance in the context of predicting changes in NCB. For the cohort that worsened NCB (n = 102), top baseline variables were cholesterol (total and HDL), white blood cell count, psoriasis area severity index score, and diastolic blood pressure. Top predictors of 1-year change were change in visceral adiposity, white blood cell count, total cholesterol, c-reactive protein, and absolute lymphocyte count. For the cohort that improved NCB (n = 80), the top baseline variables were HDL cholesterol related including apolipoprotein A1, basophil count, and psoriasis area severity index score, and top predictors of 1-year change were change in apoA, apoB, and systolic blood pressure. Conclusion: ML methods ranked predictors of progression and regression of NCB in psoriasis over 1 year providing strong evidence to focus on treating LDL, blood pressure, and obesity; as well as the importance of controlling cutaneous disease in psoriasis.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tao Xiang ◽  
Ming Cheng

Abstract Background Enoxaparin is an anticoagulant that falls in the class of medications called low molecular weight heparins (LMWHs), and is used to prevent or treat patients with deep vein thrombosis (DVT) and pulmonary embolism. Enoxaparin is the most widely used LMWH for DVT prophylaxis following knee or hip replacement surgery. Common side effects of enoxaparin include bleeding, petechiae at the injection site, and thrombocytopenia. However, reactive thrombocytosis is a rarely reported adverse reaction. We managed a patient who developed enoxaparin-associated thrombocytosis, which was completely resolved after treatment cessation. Case presentation A 78-year-old female was hospitalized for post-hip replacement rehabilitation. Low molecular weight heparin 40 mg/day was administered subcutaneously to prevent deep venous thrombosis (DVT). At admission, her platelet count was normal (228 × 109/L) and her white blood cell count was slightly elevated (12.91 × 109/L). Seven days after admission, the patient developed thrombocytosis, which peaked on the 14th day (836 × 109/L), while her white blood cell count had returned to normal (8.86 × 109/L). Her therapeutic regimen was reviewed, and enoxaparin was identified as a potentially reversible cause of reactive thrombocytosis. Switching from enoxaparin to rivaroxaban lead to a gradual decrease in the patient’s platelet count, which eventually returned to normal levels 16 days after enoxaparin was discontinued. No complications secondary to thrombocytosis was observed, and no conclusion was reached on the use of small doses of aspirin for antithrombotic therapy under these circumstances. Conclusion Enoxaparin-induced reactive thrombocytosis should be suspected in patients with thrombocytosis following enoxaparin administration as an anticoagulant to prevent certain complications.


Author(s):  
Dustin E Bosch ◽  
Patrick C Mathias ◽  
Niklas Krumm ◽  
Andrew Bryan ◽  
Ferric C Fang ◽  
...  

Abstract Background An elevated white blood cell count (&gt;15 thousand/μL) is an established prognostic marker in patients with Clostridium difficile infection (CDI). Small observational studies have suggested that a markedly elevated WBC should prompt consideration of CDI. However, there is limited evidence correlating WBC elevation with the results of C. difficile nucleic acid testing (NAAT). Methods Retrospective review of laboratory testing, outcomes, and treatment of 16,568 consecutive patients presenting to 4 hospitals over four years with NAAT and WBC testing on the same day. Results No significant relationship between C. difficile NAAT results and concurrent WBC in the inpatient setting was observed. Although an elevated WBC did predict NAAT results in the outpatient and emergency department populations (p&lt;0.001), accuracy was poor, with receiver-operator areas under the curve of 0.59 and 0.56. An elevated WBC (&gt;15 thousand/μL) in CDI was associated with a longer median hospital length of stay (15.5 vs. 11.0 days, p&lt;0.01), consistent with leukocytosis as a prognostic marker in CDI. NAAT-positive inpatients with elevated WBC were more likely to be treated with metronidazole and/or vancomycin (relative ratio 1.2, 95% confidence interval 1.1–1.3) and die in the hospital (relative ratio 2.9, 95% CI 2.0–4.3). Conclusions Although WBC is an important prognostic indicator in patients with CDI, an isolated WBC elevation has low sensitivity and specificity as a predictor of fecal C. difficile NAAT positivity in the inpatient setting. A high or rising WBC in isolation is not a sufficient indication for CDI testing.


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