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Chronic myeloid malignancies
Diagnosis and prognosis are supported by integrated assessment of next-generation sequencing in chronic myeloid malignancies. A real-life study
Ferrata Storti Foundation
Haematologica 2021 Volume 106(3):701-707
Sophie Vantyghem,1 Pierre Peterlin,1 Sylvain Thépot,2,3 Audrey Ménard,4 Viviane Dubruille,1 Camille Debord,4 Thierry Guillaume,1 Alice Garnier,1 Amandine Le Bourgeois,1 Soraya Wuilleme,4 Catherine Godon,4 Olivier Theisen,4 Marion Eveillard,3,4 Jacques Delaunay,5 Hervé Maisonneuve,6 Nadine Morineau,6 Bruno Villemagne,6 Stéphane Vigouroux,6 François Subiger,7 Elsa Lestang,8 Marion Loirat,8 Anne Parcelier,9 Pascal Godmer,9 Mélanie Mercier,9 Adrien Trebouet,10 Damien Luque Paz,3,11 Ronan Le Calloch,12 Lenaig Le Clech,12 Céline Bossard,13 Anne Moreau,13 Valérie Ugo,3,11 Mathilde Hunault,2,3 Philippe Moreau,1,3 Steven Le Gouill,1,3 Patrice Chevallier,1,3 Marie C. Béné3,4 and Yannick Le Bris3,4
1Hematology Clinic, Nantes University Hospital, Nantes; 2Hematology Clinic, Angers University Hospital, Angers; 3CRCINA, INSERM, CNRS, Université de Nantes, Université d'Angers, Pays de la Loire; 4Hematology Biology, Nantes University Hospital, Nantes; 5Le Confluent, Nantes; 6Hematology Clinic, Vendée Hospital Center, La Roche sur Yon; 7Biology Laboratory, Vendée Hospital Center, La Roche sur Yon; 8Hematology Clinic, Saint Nazaire Hospital, Saint Nazaire; 9Hematology Clinic, Bretagne Atlantique Hospital, Vannes; 10Hematology Clinic, Bretagne Sud Hospital, Lorient; 11Hematology Biology, Angers University Hospital, Angers; 12Hematology Clinic, Quimper Hospital, Quimper and 13Pathology Department, Nantes University Hospital, Nantes, France
ABSTRACT
Next-generation sequencing (NGS) is used to investigate the pres- ence of somatic mutations. The utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains unclear. We report the findings of an observational, multicenter study that aimed to assess the impact of somatic mutation testing by NGS in a real- life setting of chronic myeloid malignancies. A total of 177 patients were enrolled, partitioned into two overlapping groups. In group A (n=94), the indication was to search for clonal hematopoiesis, in a context of suspect- ed myelodysplastic syndrome or myeloproliferative neoplasia. In group B (n=95), the theranostic impact of somatic mutations was studied. A panel of 34 genes was used on DNA extracted from blood or bone marrow sam- ples. Within group A, the detection of clonal hematopoiesis supported the diagnosis of chronic myeloid malignancies for 31 patients while the absence of clonal hematopoiesis ruled out the suspected diagnosis in 47 patients. Within group B, NGS identified prognostically relevant somatic mutations in 32 patients, which had a therapeutic impact in 18 cases. By determining the presence or absence of somatic mutations, the applica- tion of NGS in daily practice was found to be useful for an integrated final diagnosis in 83% of the patients. Moreover, the search for somatic muta- tions had a prognostic impact that led to treatment modification in 19% of the cases. This study outlines the fact that adequate implementation of new investigations may have a significant positive medico-economic impact by enabling appropriate management of patients.
Introduction
During the past decade, high-throughput sequencing has increased knowledge on the genomic landscape of hematologic malignancies. Somatic mutations have thus become new biomarkers that are useful in clinical practice to improve diagno- sis, prognosis stratification and targeted treatment. In France, the implementation
Correspondence:
YANNICK LE BRIS
yannick.lebris@chu-nantes.fr
Received: November 12, 2019. Accepted: April 1, 2020. Pre-published: April 2, 2020.
https://doi.org/10.3324/haematol.2019.242677
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