Improvement of Standardization of Molecular Analyses in Hematology: The 10-year GBMHM French Experience

Abstract

Molecular tests have become an indispensable tool for the diagnosis and prognosis of hematological malignancies and are subject to accreditation according to the International Standard ISO 15189. National standardization of these techniques is essential to ensure that patients throughout France benefit from the same care. We report here on the experience of the GBMHM (Groupe des Biologistes Moléculaires des Hémopathies Malignes). By organizing External Evaluation of Quality (EEQ) programs and training meetings, the GBMHM has contributed to improvement and standardization of molecular tests in 64 French laboratories. A retrospective analysis of the quality-control results of 11 national campaigns spanning 10 years was performed for the 3 most frequently prescribed tests: BCR-ABL1, JAK2 V617F, and lymphoid clonality. For each test, particular attention was placed on comparing methodologies and their evolution throughout the period. The establishment of the BCR-ABL1, JAK2 V617F, and lymphoid clonality EEQ programs and the associated training meetings have initiated a process of collective standardization concerning the methods of implementation (JAK2 V617F) and the interpretation and formulation of results (lymphoid clonality). In addition, it resulted in objective improvement in technical performance (BCR-ABL1). Our evaluation of the impact of these EEQ programs demonstrates that it is possible to obtain reproducible values across different laboratories in France by applying national recommendations. To our knowledge, this is the first publication that evaluates the impact of a national quality assurance program on improving molecular results in hematology.

Targeted High-throughput Sequencing for Hematological Malignancies: A GBMHM Survey of Practice and Cost Evaluation in France

“…The GBMHM technological platform is accredited as a provider of external quality assessment (EQA) by the HAS CA. Combined education and bi‐annual EQA by the onco‐hematology diagnostic community have allowed collective, nationwide, improvement in standardization and harmonized reporting of both CE‐marked and, predominantly, in‐house IVD testing 3 …”

“…Combined education and bi-annual EQA by the onco-hematology diagnostic community have allowed collective, nationwide, improvement in standardization and harmonized reporting of both CE-marked and, predominantly, in-house IVD testing. 3 …”

“…To ensure access to innovative in-vitro diagnostics (IVDs) before their inscription on the national biological laboratory 1 DRCI-URC Eco Ile-de-France, Assistance Publique-Hôpitaux de Paris (AP-HP), France 2 Hospices Civils de Lyon, Hôpital Lyon Sud, Service d'hématologie biologique, France 3 Hôpital Cochin, Hématologie Biologique, AP-HP, Université, Paris Cité, France 4 Univ Angers, Nantes Université, CHU Angers, Inserm, CNRS, France 5 Hématologie Biologique, AP-HP, Necker-Enfants Malades Hospital, Paris, France 6 Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, France tests and procedures schedule (NABM), the French Ministry of Health set up in 2015 a conditional coverage mechanism for a referenced list of innovations not yet included in the national nomenclature (RIHN).…”

“…Both RuBIH programs have been undertaken with the French association of molecular biologists for hematological malignancies (Groupe des Biologistes Moléculaires des Hémopathies Malignes [GBMHM]), a nonprofit network, which organizes continuing medical education, concerted actions, and quality assessment 3 for molecular diagnostics of hematological cancers. During the RuBIH1 program, the clinical and diagnostic hematology community, under the aegis of the French Hematology Society (SFH), established guidelines for appropriate diagnostic prescriptions 2 and undertook HTA assessment of reverse transcription-PCR quantification of fusion transcripts such as BCR-ABL, 4 DNA point mutation quantification of single targets such as JAK2 V617F and immunogenetic detection of lymphoid clonality.…”

Very short insertions in the FLT3 gene are of therapeutic significance in acute myeloid leukemia

“…( Figure 1 A; supplemental Table 1 ). 16 Among these patients, 22 (1.1%) were found to have very short in-frame insertions (VSI) within FLT3 , resulting in a gain of only 1 or 2 amino acids, a phenomenon that has already been described but not specifically studied ( supplemental Table 2 ). 14 , 15 Interestingly, FLT 3 -VSIs were mainly observed at amino acid positions 572 to 578 and 591 to 599 in 25% and 60% of the analyzed cases in our cohort, respectively ( Figure 1 B).…”