Original Title: Avis - Dégranulation des cellules NK (Natural Killer)

Authors' objectives: A request for the introduction of a new assay into the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the " Répertoire ") was made by the Centre hospitalier universitaire Sainte-Justine (CHUSJ) and transmitted to the Institut national d'excellence en santé et en services sociaux (INESSS) through the assessment mechanism for new medical biology assays. The mandate given is to assess the NK cell degranulation assay, measured by cytometry using the CD107a marker. This is a functional assay for diagnostic screening to determine the primary nature of hemophagocytic lymphohistiocytosis (HLH) in patients with specific symptoms of this disease. Since this assay is not included in the Répertoire, the Ministère de la Santé et des Services sociaux (MSSS) deems it necessary that the usefulness of testing NK cell degranulation by measuring the CD107a marker be assessed.

Authors' results and conclusions: RESULTS: A total of five studies were included to assess clinical validity. The CD107a NK cell degranulation assay identifies a subgroup of patients with a primary form of HLH. The sensitivity and specificity of the assay range from 74% to 96% and 73% to 88%, respectively. Positive predictive values ranged from 20.3% to 89%, while negative predictive values ranged from 81% to 98.9% with an area under the curve ranging from 0.860 to 0.894. By coupling the NK cell degranulation assay with the perforin expression assay, the ability to identify primary forms of HLH could be improved. There are no published data to assess the clinical utility of the NK cell degranulation assay. However, according to the experts consulted, it allows for the rapid identification of patients with primary HLH and contributes to the prompt administration of appropriate pharmacological treatment or to initiating the transplant process, particularly by anticipating the search for a donor, since the patient's survival depends on it. This would improve the patient's survival prognosis. The guidelines consulted mention that the NK cell degranulation assay is a functional assay that is better suited to the diagnostic screening of a primary HLH compared to other such assays [NACHO, 2020; ASH, 2021; Hines et al., 2021]. No studies assessing the efficiency of the NK cell degranulation assay for the diagnostic confirmation of primary HLH were identified. However, according to the scientific literature and the experts consulted, the management of certain patients could be optimized. However, the INESSS cannot conclude on the efficiency of the assay. Considering that the NK cell degranulation assay would be in addition to the current functional assays, additional costs of approximately $116K over the first three years are envisaged.

Authors' recommendations: RESULTS: A total of five studies were included to assess clinical validity. The CD107a NK cell degranulation assay identifies a subgroup of patients with a primary form of HLH. The sensitivity and specificity of the assay range from 74% to 96% and 73% to 88%, respectively. Positive predictive values ranged from 20.3% to 89%, while negative predictive values ranged from 81% to 98.9% with an area under the curve ranging from 0.860 to 0.894. By coupling the NK cell degranulation assay with the perforin expression assay, the ability to identify primary forms of HLH could be improved. There are no published data to assess the clinical utility of the NK cell degranulation assay. However, according to the experts consulted, it allows for the rapid identification of patients with primary HLH and contributes to the prompt administration of appropriate pharmacological treatment or to initiating the transplant process, particularly by anticipating the search for a donor, since the patient's survival depends on it. This would improve the patient's survival prognosis. The guidelines consulted mention that the NK cell degranulation assay is a functional assay that is better suited to the diagnostic screening of a primary HLH compared to other such assays [NACHO, 2020; ASH, 2021; Hines et al., 2021]. No studies assessing the efficiency of the NK cell degranulation assay for the diagnostic confirmation of primary HLH were identified. However, according to the scientific literature and the experts consulted, the management of certain patients could be optimized. However, the INESSS cannot conclude on the efficiency of the assay. Considering that the NK cell degranulation assay would be in addition to the current functional assays, additional costs of approximately $116K over the first three years are envisaged.

Authors' methods: The assessment process included a review of the scientific literature, a search of the grey literature and consultations with experts and other stakeholders. The methodology was designed around four assessment questions, including clinical validity, clinical utility, organizational arrangements, and the economic impact of introducing the NK cell degranulation assay into managing patients with HLH. A budgetary impact analysis considering the costs associated with the introduction of the assay to the Répertoire was also undertaken. Costs were projected over a three-year time frame from a health care system perspective. All scientific, contextual, and experiential data were interpreted and assessed using a synthesis grid to guide the deliberative process of the Comité scientifique permanent (CDP) – Approches Diagnostiques et dépistage for the development of recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/degranulation-des-cellules-nk-natural-killer.html

Year Published: 2023

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/degranulation-des-cellules-nk-natural-killer.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

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)