[Report: optical genome mapping - diagnosis and prognostic stratification of hematological malignancies]

Nieminen J, Rousseau A, Bélanger S
Record ID 32018004910
Original Title: Avis - Cartographie optique du génome : Diagnostic et stratification pronostique des hémopathies malignes
Authors' objectives: The clinical cytogenetics laboratory at Hôpital Maisonneuve-Rosemont (CIUSSS de l'Estde-l'Île-de-Montréal) submitted a new request for an analysis to be included in the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the « Répertoire »). The request was transmitted to the Institut national d'excellence en santé et en services sociaux (INESSS) in accordance with the evaluation mechanism for new medical biology analyses. The mandate given was to evaluate optical genome mapping (OGM) analysis for the detection of clinically significant chromosomal abnormalities in hematological malignancies. As this test is not listed in the Répertoire, the Ministry of Health and Social Services (MHSS) considers it necessary to evaluate the relevance of OGM analysis.
Authors' results and conclusions: RESULTS (#1 POPULATION DIMENSION): Hematological malignancies are a heterogeneous group of cancers of blood cells and their precursors. The hematological malignancies covered by the proposed analysis include acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative neoplasia (MPN) and multiple myeloma (MM). To confirm the specific condition underlying the patient's signs and symptoms, a differential diagnosis is performed. Particularly useful in this context are the search for mutations using sequencing techniques, and the search for chromosomal abnormalities using cytogenetic analyses, mainly karyotype analysis and fluorescence in situ hybridization (FISH). The various genetic abnormalities identified help to diagnose and classify hematological malignancies, clarify prognosis, and determine treatment strategies. Generally, the first step in cytogenetic analysis in Quebec laboratories is the karyotype. This is followed by a series of FISH analyses. The diagnosis of hematological malignancies increasingly relies on the ability of laboratories to detect the majority of clinically significant genetic abnormalities. The technical, human, and material resources required to obtain the maximum amount of information from the samples taken, and the ability to conduct these analyses rapidly without compromising analytical performance, represent a challenge for laboratories. For rapid, accurate and reliable diagnosis of hematological malignancies, solutions are needed that enable high-resolution genome-wide analysis, are fast, do not discriminate between different types of abnormalities, are inexpensive in terms of equipment and labor, offer ease of analysis, and require samples that are easy to collect and store. (#2 CLINICAL DIMENSION): The procedure in question is optical genome mapping (OGM), which detects structural variants (SVs) and copy number variants (CNVs) in genome-wide DNA (gDNA). This molecular analysis method uses high molecular weight genomic DNA. Following fluorophore labelling, structural variants can be visualized using the SaphyrTM instrument (Bionano) and its bioinformatics platform. The requesting laboratory intends to replace nearly 80% of traditional local cytogenetic tests, such as karyotype and FISH, with OGM for patients diagnosed with AML, ALL, MDS, MPN and MM hematological malignancies, regardless of whether the diagnosis is de novo or secondary to prior therapy. (#3 ORGANIZATIONAL DIMENSION): The expertise required for OGM analysis is already in place in cytogenetic laboratories across Quebec. With appropriate training and a learning curve, existing staff will be able to perform the analyses. OGM could provide a partial response to the current issues of labor shortages and increasing numbers of analyses to be processed, by enabling a complete mapping (including rare and cryptic anomalies) to be obtained in a single analysis. This would cut technical time for each patient by more than 50% and provide much more complete results in significantly less time. (#4 SOCIOCULTURAL DIMENSION): The OGM technology is very popular in Quebec, and several laboratories have expressed a desire to acquire this technology if it is introduced into the Répertoire. (#5 ECONOMICAL DIMENSION ): No studies evaluating the efficiency of OGM for the detection of clinically significant structural variants in haematological malignancies have been identified. Considering that OGM performs at least as well as standard cytogenetic tests, and could therefore replace them, it is estimated that its use would result in a cost reduction ranging from $212 to $1,274, depending on the hematological malignancy. The addition of OGM to the Répertoire could generate savings of $0.6 to $1.9 million over the first three years.
Authors' recommendations: Based on the above findings, INESSS recommends that the Minister introduce OGM analysis into the Répertoire if the following conditions are met: The recommendation applies to hematological malignancies;  The clinical validation studies in progress at the requesting laboratory have been completed and the analysis meets the requirements of ISO 15189;  The tests should only be conducted in laboratories that have the necessary expertise and meet current standards;  As OGM analysis cannot completely replace traditional cytogenetic testing, laboratories implementing OGM analysis will need to ensure that they retain the expertise required to continue offering traditional cytogenetic testing services;  To ensure that access is equitable, and that practices and policies are harmonized across Quebec, the MHSS should set up a committee to oversee the deployment of this technology. In particular, issues relating to the disclosure of results should be part of this committee's mandate.
Authors' methods: The evaluation approach included a review of the scientific literature, a grey literature search and consultations with experts and other stakeholders. The methodology was deployed around eight evaluation questions, focusing on the population, clinical, organizational, economic, and socio-cultural dimensions of OGM analysis in the context of diagnosis and prognostic stratification of hematological malignancies. A budgetary impact analysis was also conducted, considering the costs associated with introducing the test into the Répertoire. The costs were projected over a three-year time horizon from the perspective of a healthcare system. All scientific, contextual, and experiential data were interpreted and assessed using a synthesis grid to guide the deliberative process of the Standing Deliberative Committee - Diagnostic approaches and screening ("Comité délibératif permanent - Approches diagnostiques et dépistage") for the development of recommendations.
Project Status: Completed
Year Published: 2023
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Canada
Province: Quebec
MeSH Terms
  • Leukemia
  • Hematologic Neoplasms
  • Leukemia, Myeloid
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myeloproliferative Disorders
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Chromosome Mapping
  • Practice Guidelines as Topic
  • Genomics
Organisation Name: Institut national d'excellence en sante et en services sociaux
Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369
Contact Name: demande@inesss.qc.ca
Contact Email: demande@inesss.qc.ca
Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)
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