scholarly journals Assessing Bone Marrow Activity in Patients with Essential Thrombocythemia and Prefibrotic Myelofibrosis: Results of a Pilot Study of [18F]FLT PET

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4623-4623
Author(s):  
Mohamed A Yassin ◽  
Sadek A Nehmeh ◽  
Abdulqadir Jeprel Nashwan ◽  
Samah Kohla ◽  
Shehab Fareed Mohamed ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lumbar Spine ◽  
Essential Thrombocythemia ◽  
Gold Standard ◽  
Myeloproliferative Neoplasms ◽  
Bone Marrow Examination ◽  
World Health ◽  
Invasive Technique ◽  
Gold Standard Method ◽  
Flt Pet

Abstract Background Among several groups of clinicians and hematopathologists a conflict of opinion has been repeatedly expressed concerning the validity of bone marrow (BM) features characterizing myeloproliferative neoplasms (MPNs). In this regard, controversy is mainly focused on the distinction between essential thrombocythemia (ET) and pre-fibrotic/early primary myelofibrosis (pre-PMF) Although other groups confirmed the characteristic BM features and emphasized the clinical impact to discriminate both MPN subtypes the existence of pre-PMF has been questioned, including clinical usefulness and particularly reproducibility of the corresponding diagnostic guidelines. In this context, it has been criticized that the MPN classification proposed by the World Health Organization (WHO), updated in 2008 and revised in 2016,was focused on BM morphology as the gold standard of diagnosis. The current standard for follow-up of these patients is based on pathological markers (peripheral blood counts and/ bone marrow histomorphology) and molecular markers. Bone marrow examination is the gold standard method to assess the disease's extent; it offers detailed information about cellularity, the morphology of each lineage, the degree of fibrosis, and the transformation and dysplastic features. However, many patients are reluctant to go for this invasive technique which precludes precise disease activity assessment at the desirable frequencies. A non-invasive technique that can offer reliable prognostic and predictive information about the disease is lacking. The objective of this study is to explore the diagnostic value of FLT-PET in malignant hematopoiesis of Pre-PMF and ET. The potential to use FLT-PET metrics to differentiate between Pre-PMF and ET is assessed Methods A total of 13 patients (mean age of 43.23 ± 14.42 years, 7 males and 6 females) with Essential Thrombocythemia (ET) and/or Prefibrotic myelofibrosis were included in this study. One male subject was excluded due to an inconclusive diagnosis. The study was approved by the institutional review board. Written informed consents were obtained from all subjects. Each subject underwent FLT PET imaging as well as bone marrow examination (gold standard) and all were tested for JAK2v617F , CALR and MPL . Semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen and Lumbar spine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <0.05 is considered to be statistically significant. Discussion: Pre-PMF and ET exhibited different features of bone marrow; however, this is not always easy to judge objectively, making pathologists' distinction often suboptimal. And in another scenario, bone marrow which is mandated for diagnosis, cannot be obtained due to technical issues or patient-related factors. In the 2016 revised classification,pre-PMF was recognized as a separate entity, distinct from ET. Thrombosis and hemorrhage represent two of the main causes of morbidity and mortality in patients with ET. Incidence of arterial and venous thrombosis prior to diagnosis revealed no significant differences (23% /20 and 9/8%) in WHO-defined ET compared with pre-PMF; thrombotic complications were also similar during the follow-thrombosis is not significantly different, whereas bleeding is more frequent in pre-PMF.From clinical prespective it is important to differentiate between the two categories. Results The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P>0.05). In contrast, TLG measurements in the LSpine were statistically different (P=0.013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion TLG of the Lumbar Spine in FLT PET images is a potential quantitative parameter to discriminate between ET and PRE-PMF patients Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals A review of current knowledge of myeloproliferative disorders in the horse

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Katy Satué ◽  
Juan Carlos Gardon ◽  
Ana Muñoz
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Chronic Granulocytic Leukemia ◽  
Current State ◽  
Multiple Cell ◽  
Health Organization

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

Pegifna Promotes Proliferation and Myeloid Differentiation In Human Hematopoietic Progenitors In Patients With Polycythemia Vera and Essential Thrombocythemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2843-2843
Author(s):  
Katherine King ◽  
Sabina Swierczek ◽  
Katie Matatall ◽  
Kimberly Hickman ◽  
Margaret A. Goodell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Pegylated Interferon ◽  
Hematopoietic Stem ◽  
Financial Compensation ◽  
Specific Differentiation ◽  
Allelic Burden

Abstract The myeloproliferative neoplasms, polycythemia vera (PV) and essential thrombocythemia (ET), are characterized by clonal hematopoiesis that is often associated with a JAK2V617F mutation, although this does not appear to be a disease-initiating event. Treatment of PV and ET with pegylated interferon-alpha (pegInfα) has been shown to lead to hematological remission, a decrease in the JAK2V617F allelic burden in many cases, and even a reversion to polyclonal hematopoiesis. Despite promising therapeutic results, the mechanism of pegInfα-induced remission remains elusive. There are several potential mechanisms through which pegInfα may be acting, which include stimulating the immune system in order to more effectively suppress the aberrant PV clones, enhancing the activation of normal hematopoietic stem cells (HSCs), or by selectively suppressing the mutant clones. It has been previously reported that PV patients on pegInfα have an increased number of CD4+CD25+Foxp3+ T regulatory cells (Tregs) in the peripheral blood as compared to untreated or hydroxyurea treated patients (Riley Blood, 2011), which suggests that PegIFNa maybe altering immunity against the mutated clone. However, we have found that interferon treatment leads to increased proliferation of HSCs and myeloid-specific differentiation in mice (Baldridge Nature, 2010). If this finding is also true in humans, it suggests the return to polyclonality after pegInfα could also involve an increase in normal HSC proliferation. In order to address this question, we are studying the effects of pegInfα treatment on the Tregs and HSCs of PV and EV patients, when compared to hydroxyurea or untreated patients. Previously we showed that pegInfα treatment reduced the JAK2V617F allelic burden in 17 out of 32 patients. Of the 13 female patients for which clonality could be assessed, one developed polyclonal hematopoiesis with three-fold reduction of JAK2V617F allelic burden, but one developed polyclonal hematopoiesis during therapy despite no reduction in the JAK2V617F allelic burden, suggesting that pegInfα treatment is able to affect both pre-JAK2V617F clones and JAK2V617F-positive PV clones. We have now assessed changes in the HSC population in response to pegInfα treatment. Upon analysis of bone marrow samples from these same pegInfα or hydroxyurea treated patients, we found that the number of HSCs (CD45+CD34+CD38-) was increased in patients treated with pegInfα. Further we saw a decrease in the percent of quiescent HSCs in the pegInfα treated samples, measured by the percentage of cells in G0, suggesting a more actively proliferating HSC population. In agreement with these data, our RNA analysis of the HSCs showed an increase in the expression of cell cycle genes in response to short-term pegInfα treatment. In addition to this apparent increase in HSC proliferation, we also saw an increase in the number of colonies formed in methocult media from the bone marrow samples of the pegInfα treated patients, suggesting an increase in myeloid specific differentiation. When we analyzed the RNA of patients who had received long-term pegInfα treatment, we saw a transcriptional profile that was indicative of cell death. Taken together, these data suggest a model in which pegInfα treatment is allowing for a return to polyclonal hematopoiesis by inducing cell division and differentiation of normal HSCs, while suppressing the pre-JAK2V617F or JAK2V617F-positive PV and ET clones, possibly by promoting apoptosis or inducing an immune-mediated cell death. Our findings do not exclude other potential mechanisms for salutary effects of pegInfα for treatment of PV and ET (see accompanying abstract by Swierczek et al). Disclosures: Swierczek: University of Utah: No financial compensation , No financial compensation Patents & Royalties.

scholarly journals MPL W515 L/K mutations in myeloproliferative neoplasms

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sohaila Eldeweny ◽  
Hosny Ibrahim ◽  
Ghada Elsayed ◽  
Mohamed Samra
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Ethnic Groups ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Myelogenous Leukemia ◽  
Egyptian Population ◽  
Ph Chromosome ◽  
Pathological Variant

Abstract Background Myeloproliferative neoplasms (MPNs) describe a group of diseases involving the bone marrow (BM). Classical MPNs are classified into chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). This classification is based on the presence of Philadelphia (Ph) chromosome (BCR/ABL1). CML is BCR/ABL1-positive while PV, ET, and PMF are negative. JAK2 p. Val617Phe pathological variant is the most associated mutation in BCR/ABL1-negative MPNs. The frequency of JAK2 p. Val617Phe is 90–95% in PV patients, 50–60% in ET, and 40–50% in patients with PMF. Studies on MPL gene led to the revelation of a gain of function pathological variants in JAK2 p. Val617Phe-negative myeloproliferative neoplasms (MPNs). MPL p. W515 L/K pathological variants are the most common across all mutations in MPL gene. The prevalence of these pathological variants over the Egyptian population is not clear enough. In the present study, we aimed to investigate the prevalence of MPL p. W515 L/K pathological variants in the Philadelphia (Ph)-negative MPNs over the Egyptian population. Results We have tested 60 patients with Ph-negative MPNs for MPL p. W515 L/K pathological variants. Median age was 51 (22–73) years. No MPL p. W515 L/K pathological variants were detected among our patients. JAK2 p. Val617Phe in PV and PMF patients showed significantly lower frequency than other studies. Splenomegaly was significantly higher in ET patients compared to other studies. Conclusion MPL p. W515 L/K pathological variants are rare across the Egyptian Ph-negative MPNs, and further studies on a large number are recommended. MPN patients in Egypt are younger compared to different ethnic groups.

scholarly journals Autoimmune myelofibrosis associated with autoimmune hemolytic anemia successfully treated with ruxolitinib

2021 ◽  
Author(s):  
Shuku Sato ◽  
Wataru Kamata ◽  
Yotaro Tamai
Keyword(s):  
Bone Marrow ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Transforming Growth Factor ◽  
Myeloproliferative Neoplasms ◽  
Bone Marrow Examination ◽  
Coombs Test ◽  
Bone Marrow Fibrosis ◽  
Cytokine Levels ◽  
Antiglobulin Test

Abstract A 55-year-old man suffered from dyspnea, general malaise, and jaundice. His laboratory date showed pancytopenia and hemolytic anemia, and computed tomography showed splenomegaly. Bone marrow examination revealed myelofibrosis (MF)-1. The hemolytic anemia was diagnosed as IgM autoimmune hemolytic anemia (AIHA) with negative direct and indirect Coombs test but positive IgM-direct antiglobulin test. We started ruxolitinib 20 mg, which improved not only bone marrow fibrosis, symptoms related to myeloproliferative neoplasms and splenomegaly, but also AIHA. AIHA may be associated with Autoimmune MF (AIMF), and cytokines such as transforming growth factor (TGF)-β are thought to be involved in such cases. This case suggests that ruxolitinib may improve the cytokine levels and may lead to the treatment of AIHA as well as AIMF.

Essential Thrombocythemia in Patients with Platelet Counts below 600×109/L: Applicability of the 2008 World Health Organization Diagnostic Criteria Proposal

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5239-5239
Author(s):  
Mi Kwon ◽  
Santiago Osorio Prendes ◽  
Carolina Muñoz ◽  
Jose Manuel Sanchez ◽  
Monica Ballesteros ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Essential Thrombocythemia ◽  
World Health ◽  
Jak2 Mutation ◽  
Who Criteria ◽  
Platelet Counts ◽  
Bone Marrow Histology ◽  
Health Organization

Abstract WHO criteria defines platelet counts above 600×109/L as the threshold for essential thrombocythemia (ET) diagnosis. It has been argued that such threshold excludes a number of patients with ET with platelet counts below 600×109/L. Recently, a proposal for revision of the World Health Organization (WHO) diagnostic criteria for ET has been published, which includes the combination of histological bone marrow study and testing of JAK2 mutation. Design and methods: Retrospective analysis of 92 patients with ET diagnosis between 1989 and February 2008, isolating the subgroup of patients with platelet counts below 600×109/L. The aim of this study was to analyze the applicability of the 2008 WHO criteria in this subgroup. Results: Of the 92 patients, 30 patients did not fulfill the WHO criteria due to platelet counts <600×109/L and in some cases also due to the coexistence of alternative causes of thrombocytosis. There were no significant differences between the entire group and the borderline platelet count subgroup in demographics, clinical and laboratory parameters (Table 1). The median age of the borderline platelet count group was 51 years (range 19–83 years) and 20 were female (70%). At diagnosis their median platelet count was 527×109/L (range 424–597). Fifteen patients (50%) showed the presence of JAK2 mutation. Remarkably, 74% of the patients presented as high-intermediate risk at diagnosis. From the 30 patients who did not fulfill the WHO criteria due to low platelet counts, 26 (87%) satisfied the modified criteria allowing ET diagnosis. Among them, 1 patient showed an alternative cause of thrombocytosis, however JAK2 mutation was positive confirming the primary cause of the disorder. Four patients remained not fulfilling the new criteria due to insufficient bone marrow sample or incompatible histology, however one of these patients showed JAK2 mutation confirming ET. The median follow-up was 2.54 years (range 0.07–18.7). During this period, none of the 30 patients had a spontaneous decrease of platelet count to within the normal range. Furthermore, transformation from ET to IMF was observed in 2 cases supporting the diagnosis of ET. During follow-up, 27 out of 30 patients were treated with antiaggregating drugs, 3 with antithrombotic therapy, and 20 with myelosuppressive therapy. The 11 patients who did not receive myelosuppressive therapy remained with platelet counts above 400×109/L. Conclusions: In our study, patients with platelet counts below 600×109/L did not show significant differences compared with the whole ET patients group. This subgroup can be diagnosed as having ET following the 2008 WHO criteria. The detection of JAK2 mutation in this setting enables the accurate diagnosis not only in cases with borderline thrombocytosis but more importantly in cases with alternative potential causes and also in cases where bone marrow sample is not available or incompatible. This observation raises de question of the role of bone marrow histology as a subjective diagnostic tool in ET diagnosis as opposed to JAK2 mutation detection. In JAK2 negative patients, subsequent follow-up of untreated patients confirmed the diagnosis since platelet counts remained high. The modified criteria facilitates the clinician to make an early diagnosis of ET in this subgroup of patients. Furthermore, a high proportion of these patients may be at risk of vascular complications, who may beneficiate from being correctly treated. TABLE 1 Total of patients Platelet count <600×10e9/L Number 92 30 Female (number, %) 59 (64%) 20 (70%) Age (median, range) 51 (19–84) 51 (19–83) Risk Low 26 (28%) 8 (26%) Intermediate 21(22%) 6 (19%) High 45 (48%) 16 (53%) Platelets ×10e9/L 693 (424–2,777) 527 (424–597) Hb g/dL 14.5 (11–18) 14.3 (11–16.8) Leucocytes ×10e9/L 8,5 (3,6–24,2) 8,5 (5,2–13,8) LDH UI/L 380 (39–1413) 337 (39–938) Splenomegaly 16 (17%) 5 (17%) JAK2 mutation 47 (51%) 15 (50%) Bone Marrow histology Celullarity >3.5 30/88 (34%) 8/28 (29%) Fibrosis grade I 2/90 (2%) 0 Compatible histology 79/89 (86%) 21/28 (75%) Abnormal Cytogenetics 2/26 (8%) 0 Symptoms 13 (14%) 4 (13%) Thrombotic event 16 (18%) 5 (17%) Haemorrhagic event 3 (4%) 0

JAK2 V617F-Negative and MPL W515K/L-Negative Essential Thrombocythemia: A High Resolution SNP Array Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5258-5258
Author(s):  
Carla AL Assaf ◽  
Els Lierman ◽  
Timothy Devos ◽  
Carlos Graux ◽  
Johan Billiet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Essential Thrombocythemia ◽  
Copy Number ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Snp Array ◽  
Jak2 V617f ◽  
Common Mutation ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Array Data

Abstract Background JAK2 V617F is the most common mutation in essential thrombocythemia (ET), occurring in approximately 50 % of cases. Second to JAK2 V617F is MPL W515K/L, accounting for about 10 % of cases. The molecular cause of the remaining ET cases is still largely unknown. Aims We sought to investigate JAK2 V617F-negative and MPL W515K/L-negative ET for regions of copy number variations (CNV) and loss of heterozygosity (LOH). Methods We studied blood or bone marrow samples from a series of 64 JAK2 V617F-negative and MPL W515K/L-negative ET cases. They were subjected to 2.7M SNP array by Affymetrix, which has 2,761,979 copy number markers including 400,103 SNP markers. The array data were analyzed for recurrent CNVs with Array Studio (OmicSoft), and for individual CNVs or recurrent LOHs (≥3 Mbs) with the Chromosome analysis suite (ChAS, Affymetrix). Results Only 8 recurrent gains were identified, in 5/64 patients. Interestingly, the most common gain, occurring in 5 cases was a gain of chr7 q22.3, including the gene encoding Nicotinamide phosphoribosyltransferase (NAMPT). NAMPT is known to be overexpressed in several cancers such as multiple myeloma. It catalyzes the rate-limiting step of the nicotinamide adenine dinucleotide (NAD+) biosynthesis pathway. It is also required for cell growth and survival. We checked in the 5 patients for NAMPT amplification by quantitative PCR (qPCR) on genomic DNA in comparison to controls and by normalizing to ALB and RPPH1. We were able to validate the gain in 2/5 patients. The gain in these 2 patients was demonstrated to be acquired by qPCR of NAMPT in buccal swab DNA. Other recurrent gains involved regions of chromosomes 2, 5, 7, 12, 13, and 22. These gains included, amongst others, LCP1 on chr13 q14.3 and CYTIP on chr2 q24.1, occurring in 2/64 and in 3/64 respectively. We also checked for non-recurrent gains and losses in our cohort. This analysis generated a total of 8 CNVs in 6 different patients, comprising 5 regional gains in chromosomes 2, 8, 12, and 15 and 3 regional losses in chromosomes 5, 8 and 11. The array data were also analyzed for recurrent LOHs on ChAS, yielding 17 recurrent copy neutral LOHs (CN-LOH) in 35 patients (circos plot). The most common CN-LOH region was on chromosome 3 appearing in 8 patients. Other CN-LOH regions involved chromosomes 1, 2, 3, 4, 5, 6, 7, 10, 12, 15, and 17 and they occurred in 2-5/64 patients. However, as small regions of CN-LOH can be constitutional, we suspect that most of these CN-LOH regions are not acquired. The largest region of CN-LOH observed was 12 Mbs in size. Conclusions Previous studies in unselected series of BCR-ABL1-negative myeloproliferative neoplasms have shown that copy number alterations are rare in ET as well as in polycythemia vera. In this series of 64 JAK2 V617F-negative and MPL W515K/L-negative ET patients we found recurrent gains not reported previously in the database of genomic variants in only 8% of patients, and small areas of CN-LOH in ∼55% of cases. However, most of the latter probably are constitutional. Our SNP array study provides further evidence that gains, losses or CN-LOH of small genomic regions do not play an essential role in the pathogenesis of the majority of JAK2 V617F-negative and MPL W515K/L-negative ET. However, the low frequency of megakaryocytes and unknown level of clonal involvement of the myeloid compartment in JAK2 V617F-negative and MPL W515K/L-negative ET bone marrow remain a caveat. Next generation sequencing technology is expected to bring new insights on the molecular pathogenesis of this elusive ET subset. Circos plot showing the recurrent CN-LOHs Left half represents a total of 35 patients carrying recurrent CN-LOHs and the right half represents the chromosomes and their associated properties. Right outermost layer depicts 1+log-gene density (min, 1; max 42) where cancer, OMIM and other genes are colored in red, blue and green respectively. Right middle and innermost layers designates SNP density (blue, values < 0,02; gray values, <0,06; red values >0,06; max scale 0,013) and absolute SNP numbers (min, 1; max, 12074) per windows of 50kb. Each 5Mb distance is marked with a tick underneath the innermost layer. Links from each chromosome are colored differently. Regions that are more confined on the same chromosome are least transparent and regions that are shared by more patients are drawn on top of lesser links. Disclosures: No relevant conflicts of interest to declare.

Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 60-70 ◽  
Author(s):  
Bridget S. Wilkins ◽  
Wendy N. Erber ◽  
David Bareford ◽  
Georgina Buck ◽  
Keith Wheatley ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Essential Thrombocythemia ◽  
Who Classification ◽  
Interobserver Variability ◽  
Interobserver Reliability ◽  
Diagnostic Category ◽  
Jak2 V617f ◽  
World Health ◽  
Major Hemorrhage ◽  
Fibrotic Process

The role of histopathology in the diagnosis of essential thrombocythemia (ET) is controversial, and there has been little attempt to quantitate interobserver variability. Diagnostic bone marrow trephine biopsy specimens from 370 patients with ET by Polycythemia Vera Study Group (PVSG) criteria were assessed by 3 experienced hematopathologists for 16 different morphologic features and overall diagnosis according to the World Health Organization (WHO) classification. Our results show substantial interobserver variability, particularly for overall diagnosis and individual cellular characteristics such as megakaryocyte morphology. Reticulin grade was the dominant independent predictor of WHO diagnostic category for all 3 hematopathologists. Factor analysis identified 3 independent factors likely to reflect underlying biologic processes. One factor related to overall and lineage-specific cellularity and was significantly associated with JAK2 V617F status (P < .001), a second factor related to megakaryocyte clustering, and a third was associated with the fibrotic process. No differences could be discerned between patients labeled as having “prefibrotic myelofibrosis” or “true ET” in clinical and laboratory features at presentation, JAK2 status, survival, thrombosis, major hemorrhage, or myelofibrotic transformation. These results show that histologic criteria described in the WHO classification are difficult to apply reproducibly and question the validity of distinguishing true ET from prefibrotic myelofibrosis on the basis of subjective morphologic criteria. This study was registered at http://isrctn.org as #72251782 and at http://eudract.emea.europa.eu/ as #2004-000245-38.

scholarly journals Bone marrow aspiration in haematological disorders: study at a tertiary care centre

2018 ◽  
Vol 6 (7) ◽  
pp. 2361
Author(s):  
Subuh Parvez Khan ◽  
Sajad Geelani ◽  
Shareefa Akhter ◽  
Shuaeb Bhat ◽  
Saleem Hussain ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Megaloblastic Anemia ◽  
Tertiary Care ◽  
Test Procedure ◽  
Bone Marrow Aspiration ◽  
Bone Marrow Examination ◽  
Invasive Technique ◽  
Tertiary Care Centre ◽  
Female Ratio ◽  
Haematological Disorders

Background: The bone marrow examination is an essential investigation for the diagnosis and management of many disorders of the blood and bone marrow. Bone marrow aspiration (BMA) alone is usually sufficient to diagnose nutritional anaemias, and most of the acute leukaemias. Aim was to study the spectrum of haematological disorders diagnosed on bone marrow aspiration.Methods: This study was conducted in the Department of Clinical Haematology in Sher e Kashmir Institute of Medical Sciences, Kashmir for a period of 2 years from December 2015 to December 2017. Bone marrow examination of 2131 cases of suspected hematological disorders was carried out. Bone marrow was aspirated from posterior superior iliac spine under local anaesthesia. Aspirates of dry tap were excluded from the study. Aspiration smears where stained with Leishmann stain for morphological examination.Results: A total of 2131 cases were included in this study. Male to female ratio in our study was 1.9:1. The age range of cases was from 1-80 years and the mean age was 47.3 years. Anemia was the most common haematological disorder in our study accounting for 25.6% of cases followed by acute leukaemia accounting for 22.3% and multiple myeloma (13.3%). Among anemias, megaloblastic anemia was most common followed by dual deficieny anemia. Among leukaemias, acute myeloid leukaemia (13.2%) was more common than acute lymphoblastic leukaemia (9.1%).Conclusions: Bone marrow aspiration cytology is a mildly invasive technique which can diagnose many hematological and non-hematologic diseases that can be confirmed by more advanced investigations viz. serological, biochemical or molecular. It is a highly informative test procedure performed for evaluating blood and blood related diseases in our environment.

scholarly journals Performance of Cartridge Based Nucleic Acid Amplification Test for the Diagnosis of Smear Negative Suspected Tuberculosis - A Study from a Teaching Hospital in Thrissur, Kerala, India

2021 ◽  
Vol 10 (16) ◽  
pp. 1114-1118
Author(s):  
Anupama Sethumadhavan ◽  
Kavitha Paul Konikkara ◽  
Davis Paul
Keyword(s):  
Nucleic Acid ◽  
Predictive Value ◽  
Gold Standard ◽  
Sputum Sample ◽  
False Negative ◽  
Nucleic Acid Amplification Test ◽  
Nucleic Acid Amplification ◽  
World Health ◽  
Gold Standard Method ◽  
Smear Negative

BACKGROUND In India, everyday more than 6000 people develop tuberculosis (TB) and more than 600 people die of TB (2 death every 5 minutes).1 World Health Organization (WHO) has recently endorsed cartridge based nucleic acid amplification test (CBNAAT) which has the potential to lead a revolution in the diagnosis of tuberculosis. This study intends to assess the performance of CBNAAT for the diagnosis of suspected smear negative pulmonary and extra pulmonary tuberculosis. METHODS The cross-sectional study was carried out in Department of Microbiology, Government Medical College, Thrissur, Kerala, India. CBNAAT was done in district tuberculosis center, Thrissur. The study was done from December 2016 to December 2017. Samples were sent for microscopy, culture and CBNAAT. RESULTS A total of 250 patients were evaluated. Majority of the specimens collected were sputum (61.2 %) followed by bronchial wash (17.6 %). Culture was positive in 48 specimens. CBNAAT was positive in 58 specimens. Both culture and CBNAAT were positive in 47 patients. CBNAAT was negative in 1 specimen but positive in culture test. CBNAAT detected an additional 10 samples. Taking culture as gold standard, culture positives were taken as true positives and culture negatives were taken as true negatives. Accordingly, true positive was 48, true negative was 202, false positive was 10 and false negative was 1. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were respectively 97.95 %, 95.2 %, 82.75 % and 99.5 %. CBNAAT missed out a sputum sample which was culture positive. CONCLUSIONS We found CBNAAT to be an important diagnostic modality especially in smear negative patients for early diagnosis and treatment of TB. Culture of mycobacteria is considered as a gold standard method, but it takes weeks to obtain a positive result and simultaneous detection of rifampicin resistance is not possible with this method. KEY WORDS Tuberculosis, Smear Negative TB, ZN Stain, AFB, Petroff’s Method, CBNAAT, RNTCP, Culture

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