Haematological features of telomere biology disorders diagnosed in adulthood: A French nationwide study of 127 patients
Data on haematological features of telomere biology disorders (TBD) remain scarce. We describe haematological, extra-haematological characteristics and prognosis of 127 genetically confirmed TBD patients diagnosed after the age of 15. Ninety-three index cases and 34 affected relatives were included. At diagnosis of TBD, 76.3% of index cases had haematological features, half pulmonary features and a third liver features. At diagnosis, bone marrow failure (BMF) was present in 59 (46.5%), myelodysplastic syndrome (MDS) in 22 (17.3%) and acute myeloid leukaemia (AML) in 2 (1.6%) while 13 (10.2%) developed or worsened bone marrow involvement during follow-up. At diagnosis, compared to MDS/AML patients, BMF patients were younger (median 23.1 years vs. 43.8, p = 0.007), and had a better outcome (4-year overall survival 76.3% vs. 31.8%, p < 0.001). While frequencies and burden of cytogenetical and somatic mutations increased significantly in myeloid malignancies, some abnormalities were also observed in patients with normal blood counts and BMF, notably somatic spliceosome variants. Solid cancers developed in 8.7% patients, mainly human papillomavirus-related cancers and hepatocellular carcinomas. TBD is a multiorgan progressive disease. While BMF is the main haematological disorder, high-risk myeloid malignancies are common, and are, together with age, the only factors associated with a worse outcome.
Authors
- Michael Loschi
- Aurélie Plessier (ORCID: https://orcid.org/0000-0001-5656-1622)
- Élodie Lainey (ORCID: https://orcid.org/0000-0002-0224-4338)
- Gèrard Socié (ORCID: https://orcid.org/0000-0002-2114-7533)
- Vincent Alcazer (ORCID: https://orcid.org/0000-0003-1843-6286)
- P. Cathébras (ORCID: https://orcid.org/0000-0001-7570-3366)
- Delphine Lebon (ORCID: https://orcid.org/0000-0002-4073-1559)
- Ibrahima Ba (ORCID: https://orcid.org/0000-0001-5338-3883)
- Lise Larcher (ORCID: https://orcid.org/0000-0002-9461-0728)
- Alice Marceau‐Renaut (ORCID: https://orcid.org/0000-0002-3197-0785)
- Bruno Lioure
- Louis Terriou (ORCID: https://orcid.org/0000-0001-5919-9956)
- Jean Soulier (ORCID: https://orcid.org/0000-0002-8734-5356)
- Thierry Leblanc (ORCID: https://orcid.org/0000-0003-2463-9346)
- Jacques‐Emmanuel Galimard (ORCID: https://orcid.org/0000-0001-9102-4427)
- Caroline Kannengiesser (ORCID: https://orcid.org/0000-0003-2155-9383)
- Marie Passet (ORCID: https://orcid.org/0000-0003-4620-8782)
- F Maillet (ORCID: https://orcid.org/0009-0000-3150-9211)
- Flore Sicre de Fontbrune (ORCID: https://orcid.org/0000-0003-2000-1556)
- Régis Peffault de Latour (ORCID: https://orcid.org/0000-0001-6222-4753)
- Ambroise Marçais (ORCID: https://orcid.org/0000-0002-6844-7920)
- Raphaël Borie (ORCID: https://orcid.org/0000-0002-9906-0024)
- Nathalie Couque (ORCID: https://orcid.org/0000-0002-5109-0857)
- Abou-Chahla Wadih
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Côte d'Azur (FR)
- Université Paris Cité (FR)
- Université de Lille (FR)
- Hôpital Beaujon (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Centre Hospitalier Universitaire de Nice (FR)
- Sorbonne Paris Cité (FR)
- Centre Hospitalier Universitaire Amiens-Picardie (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hospices Civils de Lyon (FR)
- Hôpital Robert-Debré (FR)
- Hôpital Saint-Louis (FR)
- Centre Hospitalier Universitaire de Saint-Étienne (FR)
- European Society for Blood and Marrow Transplantation (FR)
- Université Lille Nord de France (FR)
- Université de Strasbourg (FR)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2024-09-15
- DOI
- https://doi.org/10.1111/bjh.19767
- Citations
- 5
- Primary Topic
- Telomeres, Telomerase, and Senescence
- Type
- article
- Field-Weighted Citation Impact
- 1.63