The use of genetic tests to diagnose and manage patients with myeloproliferative and myeloproliferative/myelodysplastic neoplasms, and related disorders

Abstract

This Good-Practice Paper was compiled according to the BSH process at https://b-s-h.org.uk/media/16732/bsh-guida nce-development-process-dec-5-18.pdf. The British Society for Haematology (BSH) produces Good-Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradework inggroup.org. Literature review detailsPubmed was searched from January 2018 to September 2020 using the terms (myeloproliferative OR polycythemia OR thrombocythemia OR myelofibrosis OR eosinophilia OR mastocytosis OR neutrophilia OR myelomonocytic OR eosinophilic CEL OR CNL or CMML or JMML) AND (mutation OR variant) AND (diagnosis OR prognosis). Summary information from the 1 063 hits was manually reviewed to identify 135 relevant publications. Relevant studies prior to January 2018 were identified from reviews published during the literature search period. Review of the manuscriptReview of the manuscript was performed by the BSH Guidelines Committee General Haematology Task Force, the BSH Guidelines Committee and the General Haematology sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by members of the National Cancer Research Institute (NCRI) MPN subgroup, the Chair of the NCRI MDS subgroup and lead scientists from the Genomics Laboratory Hubs in England and representative genetic testing laboratories in Wales, Scotland and Northern Ireland; these organisations do not necessarily approve or endorse the contents.

A novel algorithmic approach to generate consensus treatment guidelines in adult acute myeloid leukaemia

“…Examples include selecting the most effective sequential lines of myeloma therapy, or assisting with appropriate genetic testing in myeloproliferative (MPN) and MPN/MDS neoplasms. 19,20 Finally, the algorithmic method we present can easily be updated at regular intervals, allowing changes in drug approvals, novel therapies and emerging clinical data to be captured, providing a living guideline.…”

A Review on the Role of Molecular Genetics in the Diagnostic Workup of BCR::ABL1-Negative Myeloproliferative Neoplasms

“…Although no guidelines recommend cytogenetic or molecular testing in cases with JAK2 -negative erythrocytosis, the diagnostic workup of such cases must include the evaluation of both hereditary and acquired causes of erythrocytosis. 25 26 Algorithm of workup of cases with polycythemia is shown in Fig. 1 .…”

An overview of myelodysplastic syndromes

“…Cytogenetic and molecular genetic analysis, including fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and next-generation sequencing, may be used to identify chromosomal abnormalities or gene mutations. Cytogenetic abnormalities have been reported in 30% to 50% of patients with MDS 17. Although a wide range of genetic abnormalities are associated with MDS, the most common mutations are +8, +9, -7, del(7q), del(20q), del(13q), and isochromosome 17q 17.…”

“…17 Although a wide range of genetic abnormalities are associated with MDS, the most common mutations are +8, +9, -7, del(7q), del(20q), del(13q), and isochromosome 17q. 17 As defined by the WHO classification, several chromosomal abnormalities can be considered presumptive of MDS in patients with persistent cytopenia, even in the absence of diagnostic morphologic changes. 5,18 PROGNOSTIC INDICATORS Classification of MDS has been revised to combine the 2016 WHO criteria, National Comprehensive Cancer Network (NCCN) criteria, and the 2012 IPSS-R; the result is five risk categories: very low, low, intermediate, high, and very high.…”

“…Cytogenetic abnormalities have been reported in 30% to 50% of patients with MDS 17. Although a wide range of genetic abnormalities are associated with MDS, the most common mutations are +8, +9, -7, del(7q), del(20q), del(13q), and isochromosome 17q 17. As defined by the WHO classification, several chromosomal abnormalities can be considered presumptive of MDS in patients with persistent cytopenia, even in the absence of diagnostic morphologic changes 5,18…”