scholarly journals Diagnostic and therapeutic pitfalls in NPM1-mutated AML: notes from the field

Leukemia ◽  
2021 ◽  
Author(s):  
Brunangelo Falini ◽  
Sofia Sciabolacci ◽  
Lorenza Falini ◽  
Lorenzo Brunetti ◽  
Maria Paola Martelli
Keyword(s):  
Residual Disease ◽  
World Health ◽  
Controversial Issues ◽  
Distinct Entity ◽  
Therapeutic Decisions ◽  
Risk Stratification Model ◽  
Genetic Abnormalities ◽  
Health Organization ◽  
Chronic Myelomonocytic Leukaemia

AbstractMutations of Nucleophosmin (NPM1) are the most common genetic abnormalities in adult acute myeloid leukaemia (AML), accounting for about 30% of cases. NPM1-mutated AML has been recognized as distinct entity in the 2017 World Health Organization (WHO) classification of lympho-haematopoietic neoplasms. WHO criteria allow recognition of this leukaemia entity and its distinction from AML with myelodysplasia-related changes, AML with BCR-ABL1 rearrangement and AML with RUNX1 mutations. Nevertheless, controversial issues include the percentage of blasts required for the diagnosis of NPM1-mutated AML and whether cases of NPM1-mutated myelodysplasia and chronic myelomonocytic leukaemia do exist. Evaluation of NPM1 and FLT3 status represents a major pillar of the European LeukemiaNet (ELN) genetic-based risk stratification model. Moreover, NPM1 mutations are particularly suitable for assessing measurable residual disease (MRD) since they are frequent, stable at relapse and do not drive clonal haematopoiesis. Ideally, combining monitoring of MRD with the ELN prognostication model can help to guide therapeutic decisions. Here, we provide examples of instructive cases of NPM1-mutated AML, in order to provide criteria for the appropriate diagnosis and therapy of this frequent leukaemia entity.

scholarly journals How I diagnose and treat NPM1-mutated AML

Blood ◽  
2020 ◽  
Author(s):  
Brunangelo Falini ◽  
Lorenzo Brunetti ◽  
Maria Paola Martelli
Keyword(s):  
Myeloid Leukemia ◽  
Residual Disease ◽  
World Health ◽  
Gene Encoding ◽  
Multifunctional Protein ◽  
Myeloid Neoplasms ◽  
Mutational Status ◽  
Therapeutic Decisions ◽  
Health Organization

Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in about one-third of adult acute myeloid leukemia (AML). NPM1-mutated AML exhibits unique molecular, pathological and clinical features, that led to its recognition as distinct entity in the 2017 World Health Organization (WHO) classification of myeloid neoplasms. Although WHO criteria for the diagnosis of NPM1-mutated AML are well established, its distinction from other AML entities may be sometimes difficult. Moreover, the percentage of blasts required to diagnose NPM1-mutated AML remains controversial. According to the European LeukemiaNet (ELN), determining the mutational status of NPM1 (together with FLT3) is mandatory for accurate relapse risk assessment. NPM1 mutations are ideal targets for measurable residual disease (MRD) monitoring since they are AML-specific, frequent, very stable at relapse and do not drive clonal hematopoiesis of undetermined significance. MRD monitoring by quantitative PCR of NPM1 mutant transcripts, possibly combined with the ELN genetic-based risk stratification, can guide therapeutic decisions at post-remission stage. Furthermore, immunohistochemistry can be very useful in selected situations, such as diagnosis of NPM1-mutated myeloid sarcoma. Herein, we present four illustrative cases of NPM1-mutated AML, with the aim to address important issues on the biology, diagnosis and therapy of this common form of leukemia.

scholarly journals Flow cytometry in the diagnosis of plasma cell tumors and assessment of minimal residual disease

2021 ◽  
Vol 16 (3) ◽  
pp. 16-25
Author(s):  
L. Yu. Grivtsova ◽  
T. Yu. Mushkarina ◽  
V. V. Lunin ◽  
P. A. Zeynalova
Keyword(s):  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Residual Disease ◽  
World Health ◽  
Hematopoietic Tissue ◽  
Flow Cytometric ◽  
Plasma Cell Neoplasms ◽  
Health Organization ◽  
Minimal Residual

The article considers the features and possibilities of flow cytometric diagnostics of plasma cell neoplasms, taking into account the classification of lymphoid and hematopoietic tissue tumors of the World Health Organization, revision of 2017 and the NCCN clinical recommendations, 2021. Standardized flow cytometric protocols (the Euro-Flow conception) and algorithms for both the diagnosis of plasma cell tumors and the detection of minimal residual disease in plasma cell myeloma are described.

Sixth Edition: the New Standard

2008 ◽  
Vol 13 (1) ◽  
pp. 1-12
Author(s):  
Christopher R. Brigham ◽  
Robert D. Rondinelli ◽  
Elizabeth Genovese ◽  
Craig Uejo ◽  
Marjorie Eskay-Auerbach
Keyword(s):  
Review Process ◽  
Peer Review Process ◽  
World Health ◽  
International Classification Of Functioning ◽  
Revision Process ◽  
Sixth Edition ◽  
Impairment Ratings ◽  
Health Organization ◽  
Impairment Severity

Abstract The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, was published in December 2007 and is the result of efforts to enhance the relevance of impairment ratings, improve internal consistency, promote precision, and simplify the rating process. The revision process was designed to address shortcomings and issues in previous editions and featured an open, well-defined, and tiered peer review process. The principles underlying the AMA Guides have not changed, but the sixth edition uses a modified conceptual framework based on the International Classification of Functioning, Disability, and Health (ICF), a comprehensive model of disablement developed by the World Health Organization. The ICF classifies domains that describe body functions and structures, activities, and participation; because an individual's functioning and disability occur in a context, the ICF includes a list of environmental factors to consider. The ICF classification uses five impairment classes that, in the sixth edition, were developed into diagnosis-based grids for each organ system. The grids use commonly accepted consensus-based criteria to classify most diagnoses into five classes of impairment severity (normal to very severe). A figure presents the structure of a typical diagnosis-based grid, which includes ranges of impairment ratings and greater clarity about choosing a discreet numerical value that reflects the impairment.

The Historical Development of Burden of Treatment Compliance

2014 ◽  
Vol 19 (5) ◽  
pp. 13-15
Author(s):  
Stephen L. Demeter
Keyword(s):  
Internal Medicine ◽  
Treatment Compliance ◽  
World Health ◽  
International Classification Of Functioning ◽  
Sixth Edition ◽  
Burden Of Treatment ◽  
Specific Goal ◽  
Surrogate Measure ◽  
Health Organization

Abstract A long-standing criticism of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) has been the inequity between the internal medicine ratings and the orthopedic ratings; in the comparison, internal medicine ratings appear inflated. A specific goal of the AMA Guides, Sixth Edition, was to diminish, where possible, those disparities. This led to the use of the International Classification of Functioning, Disability, and Health from the World Health Organization in the AMA Guides, Sixth Edition, including the addition of the burden of treatment compliance (BOTC). The BOTC originally was intended to allow rating internal medicine conditions using the types and numbers of medications as a surrogate measure of the severity of a condition when other, more traditional methods, did not exist or were insufficient. Internal medicine relies on step-wise escalation of treatment, and BOTC usefully provides an estimate of impairment based on the need to be compliant with treatment. Simplistically, the need to take more medications may indicate a greater impairment burden. BOTC is introduced in the first chapter of the AMA Guides, Sixth Edition, which clarifies that “BOTC refers to the impairment that results from adhering to a complex regimen of medications, testing, and/or procedures to achieve an objective, measurable, clinical improvement that would not occur, or potentially could be reversed, in the absence of compliance.

scholarly journals Morphological Characteristics, Classifications and Difficulties in the Use of Diagnostic Criteria for Serrated Lesions of the Large Intestine

2021 ◽  
Author(s):  
Cesar de Souza Bastos Junior ◽  
Vera Lucia Nunes Pannain ◽  
Adriana Caroli-Bottino
Keyword(s):  
Diagnostic Criteria ◽  
Morphological Characteristics ◽  
World Health ◽  
Diagnostic Tools ◽  
Serrated Adenoma ◽  
The Past ◽  
The World ◽  
Serrated Lesions ◽  
Health Organization

Abstract Introduction Colorectal carcinoma (CRC) is the most common gastrointestinal neoplasm in the world, accounting for 15% of cancer-related deaths. This condition is related to different molecular pathways, among them the recently described serrated pathway, whose characteristic entities, serrated lesions, have undergone important changes in their names and diagnostic criteria in the past thirty years. The multiplicity of denominations and criteria over the last years may be responsible for the low interobserver concordance (IOC) described in the literature. Objectives The present study aims to describe the evolution in classification of serrated lesions, based on the last three publications of the World Health Organization (WHO) and the reproducibility of these criteria by pathologists, based on the evaluation of the IOC. Methods A search was conducted in the PubMed, ResearchGate and Portal Capes databases, with the following terms: sessile serrated lesion; serrated lesions; serrated adenoma; interobserver concordance; and reproducibility. Articles published since 1990 were researched. Results and Discussion The classification of serrated lesions in the past thirty years showed different denominations and diagnostic criteria. The reproducibility and IOC of these criteria in the literature, based on the kappa coefficient, varied in most studies, from very poor to moderate. Conclusions Interobserver concordance and the reproducibility of microscopic criteria may represent a limitation for the diagnosis and appropriate management of these lesions. It is necessary to investigate diagnostic tools to improve the performance of the pathologist's evaluation, for better concordance, and, consequently, adequate diagnosis and treatment.

scholarly journals Classification Maps for TDS Concentrations in the GIS Along Euphrates River, Iraq

2021 ◽  
Vol 232 (8) ◽  
Author(s):  
Ali Chabuk ◽  
Zahraa Ali Hammood ◽  
Nadhir Al-Ansari ◽  
Salwan Ali Abed ◽  
Jan Laue
Keyword(s):  
Water Quality ◽  
Drinking Water ◽  
World Health Organization ◽  
World Health ◽  
Euphrates River ◽  
Poor Water Quality ◽  
Quality Category ◽  
Health Organization ◽  
Dissolved Salts

AbstractIraq currently undergoing the problem of water shortage, although Iraq has two Rivers (Euphrates and Tigris) pass throughout most of its areas, and they have represented a major source of water supply. In the current research, to evaluate the quality of the Euphrates river in Iraq based on the values of total dissolved salts (TDS), the TDS concentrations were collected from sixteen sections along the river in the three succeeding years (2011, 2012, and 2013). The evaluation of the river was done depending on the classification of (W.H.O. (World Health Organization). (2003). Total Dissolved Salts in Drinking-water: Background document for development of W.H.O. Guidelines for Drinking-water Quality. World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland). of rivers for drinking uses. Inverse Distance Weighting Technique (IDWT) as a tool in the GIS was employed to establish the maps of the river that using interpolation/prediction for the TDS concentrations to each selected year and the average values of TDS for these 3 years. Based on the five categories of rivers’ classification of the TDS concentrations according to the (W.H.O. (World Health Organization). (2003). Total Dissolved Salts in Drinking-water: Background document for development of W.H.O. Guidelines for Drinking-water Quality. World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland), the Euphrates river was classified, and the maps of classification for the years 2011, 2012 and 2013 and the average values for 3 years were created. The average values for 3 years of TDS along the Euphrates river indicated that the sections from SC-1 to SC-4 as moderate-water-quality-Category-3, the sections from SC-5 to SC-10 as poor-water-quality-Category-4, while the sections between SC-11 to SC-16 as very poor-water-quality-Category-5. The interpolation maps showed that the Euphrates river in Iraq was ranged from moderate water quality (Category-3) to very poor water quality (Category-5).

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