scholarly journals Bone marrow histology in CALR mutated thrombocythemia and myelofibrosis: results from two cross sectional studies in 70 newly diagnosed JAK2/MPL wild type thrombocythemia patients

2019 ◽  
Vol 2 (1) ◽  
pp. 064-078
Author(s):  
Jan Jacques Michiels ◽  
Yonggoo Kim ◽  
Myungshin Kim ◽  
Francisca Valster ◽  
Vincent Potters ◽  
...  
2017 ◽  
Vol 4 (S) ◽  
pp. 159
Author(s):  
Hoang Cong Phan ◽  
Thang Thanh Phan ◽  
Toan Trong Ho ◽  
Thu Bich Tran ◽  
Thanh Thanh MCB ◽  
...  

Introduction: multiple myeloma (MM) is a B cell malignancy which characterized by accumulation of plasmocyte in bone marrow, immunoglobulins and free light chain in serum (sFLC). According to IMMWG (International multiple myeloma working group), sFLC is a criterion in diagnosis of MM. In this study, we investigate the concentration and κ/λ ratio of sFLC in newly diagnosed MM patients at Cho Ray hospital. Methods: cross-sectional study. Serum samples of 36 newly diagnosed MM patients were analyzed by Binding Site Freelite method to measure the amount of κ and λ sFLC.   Results: the median age of 36 MM patients was 61 yrs (41 – 88 yrs), with the male/female ratio was 1.2/1. MM stage III, stage II and stage I accounting for 63.9% (23/36), 27.8% (10/36), and 8.3% (3/36), respectively. Clonal IgG, IgA and IgE MM accounting for 61.1% (22/36), 30.6% (11/36), and 8.3% (3/36), respectively. We reported the median of plasmocyte in 36 cases was 35.4% (95%CI: 27.6 – 43.3). The median of concentration of κ sFLC, λ sFLC, and involved/uninvolved sFLC ratio were 1601.8 mg/L (95%CI: 104.9 – 3098.7), 900.1 mg/L (95%CI: 10.7 – 1789.5), and 191.0 (95%CI: 87.6 – 294.4), respectively. The abnormally high in sFLC concentration was reported in 97.2% MM cases (35/36), in which 55.6% cases (20/36) had increased κ sFLC, 19.4% cases (7/36) had increased λ sFLC, and 22.2% cases (8/36) had increased both κ+λ sFLC concentration. Increased involved/uninvolved sFLC ratio was found in 94.4% MM cases (34/36), in which 36.1% cases (13/36) had sFLC ratio > 100, with all involved sFLC concentration > 100 mg/L. In 3 cases of MM with kidney failure, 2 cases had increased both κ+λ sFLC, 1 case had increased κ sFLC concentration; and all of 3 cases had involved sFLC level > 5300 mg/L with sFLC ratio > 100. No significant difference of sFLC concentration and sFLC ratio among gender, stage of disease, Ig clone, or plasmocyte percent in bone marrow of MM patients. Conclusions: due to the abnormally high of sFLC concentration and sFLC ratio in MM, it is necessary to monitor frequently these parameters during treatment to prevent the risk of kidney failure for patients.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2484-2484
Author(s):  
Preetesh Jain ◽  
Hagop M. Kantarjian ◽  
Stefan Faderl ◽  
Keyur P. Patel ◽  
Guillermo Garcia Manero ◽  
...  

Abstract Abstract 2484 Background: Mutations in NPM1 (Nucleophosmin-1) have been described in about 35% of adult patients with de novo AML and 45–60 % of AML patients with a diploid karyotype. NPM1 mutations predict for achieving higher complete remission (CR) rates and better outcomes in AML. Few studies have reported on the reliability of mutated NPM1 as a marker for minimal residual disease (MRD) detection in patients with AML. Methods: We conducted a retrospective analysis of patients (n=360) with newly diagnosed AML treated at our institution between 2008 and 2012. The study was approved by the Institutional Review Board. NPM1 mutation status was determined from DNA from unsorted bone marrow (BM) aspirate samples by a PCR-based method at baseline, remission, and relapse. Genomic DNA from bone marrow samples was isolated using the Autopure extractor (QIAGEN/Gentra, Valencia, CA). Mutations in exon 12 of NPM1 were assessed by a DNA-based semi-quantitative polymerase chain reaction capillary electrophoresis (PCR-CE) assay with analytical sensitivity of approximately 2.5%. Results: Data on remission and relapse samples from 360 newly diagnosed and previously untreated patients with AML, with available NPM1 analysis on their BM at the time of initial diagnosis, was collected (see flow chart below). Median age was 60 years (range 21 – 81 years). 262 patients (72%) had de novo AML, and 98 (27%) secondary AML. Cytogenetics was diploid in 137 (38%) patients, t(8;21) in 17 (5%), inversion 16 in 26 (7%), deletion 5 alone in 27 (7.5%), del 7 and 5 in 26 (7%), deletion 7 alone in 21 (5.8%), trisomy 8 in 17 (5%) and miscellaneous in 89 (24.7%) patients, respectively. Overall, 60 (16.6%) patients including 46 of the 137 (33.5%) diploid patients had NPM1 mutation at baseline. Secondary leukemia was more common in the NPM1 wild type (30%) than in the NPM1 mutated (13%) category. When analysed by age, in patients < 60 years (n=175), OS (overall survival), EFS (event free survival) and response rates were significantly superior in NPM1 mutated subgroup (p=0.001, 0.007, 0.02 respectively), while among patients ≥ 60 years (n=185) EFS and response rates were significantly higher in the NPM1 mutated subgroup (p=0.008, 0.03 respectively). Among the patients with diploid cytogenetics who were younger than 60 years (n=60) OS, EFS and CR duration was significantly better in the NPM1 mutated subset (p=0.007, 0.007 and 0.02 respectively), while in those ≥60 years (n=77) there was no statistically significant difference in the outcomes for the NPM1 mutated and wild-type subsets. Among the 60 NPM1 mutated patients 54 (90%) including 41/46 (89%) of those with diploid cytogenetics achieved complete response (CR) or CR without platelet recovery. Thirty nine patients (including 30 with diploid karyotype) had available NPM1 status at the time of CR and all (100%) were negative for NPM1 mutation. Among the patients with mutated NPM1 at baseline who have achieved a NPM1 negative status at CR, 10/39 overall (25%) and 7/30 diploid (23%) patients relapsed. NPM1 status was available for 6 patients overall including 4 with diploid karyotype at the time of relapse. Among them, 5/6 overall (83%) and 3/4 diploid (75%) patients had mutated NPM1, while 1/6 overall (16%) and 1/4 diploid (25%) patients remained NPM1 wild type. This patient relapsed with extramedullary disease (leukemia cutis) without any BM involvement. Among the 300 patients (including 91 with diploid karyotype) with wild type NPM1 at diagnosis, none acquired a mutated NPM1 clone, either at CR or at the time of relapse. Conclusions: These data suggest that mutated NPM1 is a reliable and stable marker for the detection of MRD at the time of CR. Hence, NPM1 mutations can be used to detect MRD and their recurrence may predict pending relapse. Disclosures: Cortes: Celgene: Research Funding. Ravandi:Johnson and Johnson: Honoraria; Celgene: Research Funding.


2020 ◽  
Vol 13 (12) ◽  
pp. e237574
Author(s):  
Lokesh Vellore Dasarathan ◽  
Pranay Gaikwad ◽  
Ramesh Babu Telugu

A 20-year-old man presented in emergency with fever, abdominal pain and obstipation. On evaluation, he was found to have an acute abdomen with septic shock. The cross-sectional abdominal imaging revealed hepatosplenomegaly, pleural effusion and ascites with retroperitoneal lymphadenopathy. He was resuscitated and started on broad-spectrum antibiotics. There was no other source of infection identified elsewhere. While bacterial and fungal cultures were negative, the sputum, blood, bone marrow and ascitic fluid were positive for Mycobacterium tuberculosis following which he was started on antituberculosis therapy. Despite therapy, the patient’s clinical condition continued to deteriorate requiring critical care. In view of Landouzy’s sepsis, pulse steroid therapy was started. However, the patient’s clinical condition continued to deteriorate and developed systemic inflammatory response syndrome and multi-organ dysfunction syndrome. Despite the best efforts, the patient expired.


Heart ◽  
2021 ◽  
pp. heartjnl-2021-319359
Author(s):  
Tejas Deshmukh ◽  
Peter Emerson ◽  
Paul Geenty ◽  
Shehane Mahendran ◽  
Luke Stefani ◽  
...  

ObjectiveTo evaluate the utility of two-dimensional multiplanar speckle tracking strain to assess for cardiotoxicity post allogenic bone marrow transplantation (BMT) for haematological conditions.MethodsCross-sectional study of 120 consecutive patients post-BMT (80 pretreated with anthracyclines (BMT+AC), 40 BMT alone) recruited from a late effects haematology clinic, compared with 80 healthy controls, as part of a long-term cardiotoxicity surveillance study (mean duration from BMT to transthoracic echocardiogram 6±6 years). Left ventricular global longitudinal strain (LV GLS), global circumferential strain (LV GCS) and right ventricular free wall strain (RV FWS) were compared with traditionl parameters of function including LV ejection fraction (LVEF) and RV fractional area change.ResultsLV GLS (−17.7±3.0% vs −20.2±1.9%), LV GCS (−14.7±3.5% vs −20.4±2.1%) and RV FWS (−22.6±4.7% vs −28.0±3.8%) were all significantly (p=0.001) reduced in BMT+AC versus controls, while only LV GCS (−15.9±3.5% vs −20.4±2.1%) and RV FWS (−23.9±3.5% vs −28.0±3.8%) were significantly (p=0.001) reduced in BMT group versus controls. Even in patients with LVEF >53%, ~75% of patients in both BMT groups demonstrated a reduction in GCS.ConclusionMultiplanar strain identifies a greater number of BMT patients with subclinical LV dysfunction rather than by GLS alone, and should be evaluated as part of post-BMT patient surveillence. Reduction in GCS is possibly due to effects of preconditioning, and is not fully explained by AC exposure.


2021 ◽  
Vol 22 (2) ◽  
pp. 772
Author(s):  
Javier Conde ◽  
Marlene Schwarzfischer ◽  
Egle Katkeviciute ◽  
Janine Häfliger ◽  
Anna Niechcial ◽  
...  

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 was able to induce the secretion of IL-1β via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO2 in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Takashima ◽  
S Usui ◽  
S Matsuura ◽  
C Goten ◽  
O Inoue ◽  
...  

Abstract Background In our previous 5-year cohort study, we demonstrated that low gene expression of nerve growth factor receptor (NGFR) in peripheral leucocytes in acute coronary syndrome (ACS) predicted repetitive coronary interventions at the de novo lesions. An NGFR-positive cell has been demonstrated to reside in bone marrow (BM) stromal fraction and to be increased in peripheral blood mononuclear cell (MNCs) fraction in patients with ischemic heart disease. Purpose To investigate whether the BM-NGFR+ cell is associated with arterial remodeling and the relationship between the levels of peripheral NGFR+ cells after ACS and coronary plaque progression in an experimental and prospective clinical study. Methods and results In an experimental study, 8-week-old C57B6/J wild type male mice were subjected to irradiation with 9.6 Gy and transplantation with BM (BMT) isolated from GFP-transgenic NGFR wild type (WT) or knock-out (KO) mice at day 1. Four weeks after BMT, the right carotid artery was ligated for 4 weeks. Induced neointimal area was increased (p&lt;0.05), where cells under apoptosis were decreased (p&lt;0.05) in NGFR-KO-BMT group compared to WT-BMT group (n=4). NGFR+ cells were not detected in wild type sham-operated artery, whereas in the ligated artery in WT-BMT group NGFR+ cells assembled in the developed neointima and exclusively presented double positive with GFP, but absent in NGFR-KO-BMT group (p&lt;0.05, n=4). In a clinical study, thirty patients with ACS who underwent primary percutaneous coronary intervention (PCI) were enrolled. The peripheral blood sample was collected on days 0, 3 and 7, and 9 months follow-up and the number of NGFR+MNCs were measured by flowcytometric analysis. The plaque volume at non-targeted coronary lesion (non-TL:&gt;5 mm proximal or distal to the implanted stents) were quantitatively analysed using gray-scale intravascular ultrasound (IVUS) and Q-IVUS™ software at the acute phase and 9 months follow-up. The number of NGFR+MNCs in peripheral blood was 1.5-fold increased at day 3 (0.064±0.056%) compared to day 0 (0.042±0.030%) (p&lt;0.05). The change in normalized total plaque volume (TAVN) at non-TL at 9 months was negatively correlated with the number of NGFR+MNCs at day 0 (r=−0.51), day 3 (r=−0.51) and 9 months (r=−0.59) after ACS (p&lt;0.05). Multiple regression analysis showed that NGFR+MNCs at day 0 (β=−0.48, p=0.01) and CRP (β=−0.53, P&lt;0.01) are independent factors associating with TAVN change at non-TL at 9 months, regardless of LDL-cholesterol control level. ROC analysis revealed that NGFR+MNCs &lt;0.049 at day 0 predicted the increase of TAVN with AUC 0.78; sensitivity 0.82 and specificity 0.67. Conclusions Bone marrow-derived peripheral NGFR+ cells negatively regulate arterial remodeling through appropriate apoptosis of neointimal cells and the peripheral level of NGFR+ cells in ACS predicts plaque progression at the non-targeted lesion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): KAKENHI


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1339
Author(s):  
Kristoffer Juul Nielsen ◽  
Kathrine Kronberg Jakobsen ◽  
Jakob Schmidt Jensen ◽  
Christian Grønhøj ◽  
Christian Von Buchwald

Human papillomavirus (HPV) imposes an increased risk of developing cervical, anal and oropharyngeal cancer. In the Western world, HPV infection is currently the major cause of oropharyngeal cancer. The effectiveness of HPV vaccines for oral or oropharyngeal HPV infection is yet to be determined. This study conducted a systematic literature search in Pubmed and Embase. Studies investigating the impact of HPV vaccines on oral or oropharyngeal HPV infection were enrolled. This review reports the relative prevention percentage (RPP), including a risk of bias assessment as well as a quality assessment study. Nine studies were included (48,777 participants): five cross-sectional studies; one randomized community trial study (RCT); one longitudinal cohort study; and two case-control studies. A significant mean RPP of 83.9% (66.6–97.8%) was calculated from the cross-sectional studies, 82.4% in the included RCT and 83% in the longitudinal cohort study. Further, two case-control studies that measured antibody response in participants immunized with HPV vaccines were included. Respectively, 100% and 93.2% of participants developed HPV-16 Immunoglobulin G (IgG) antibodies in oral fluids post-vaccination. Analysis of the studies identified a significant decrease in vaccine-type oral or oropharyngeal HPV infections in study participants immunized with HPV vaccines across study designs and heterogenous populations. Further, a significant percentage of participants developed IgG antibodies in oral fluid post-vaccination.


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