The diagnostic performance of the basic versus the detailed telomere Flow <scp>FISH</scp> test in young patients with aplastic anaemia

Identifying telomere biology disorders (TBDs) in patients with aplastic anaemia (AA) is essential for guiding appropriate care. Telomere length (TL) measurement by flow cytometry with fluorescence in situ hybridization supports diagnosis, but the real-world performance of the basic test (lymphocytes and granulocytes) versus the detailed test (which includes four lymphocyte subsets) remains unclear. We retrospectively reviewed 439 patients who underwent detailed TL testing at our institution from 2008 to 2022. Haematological disease was present in 87%, with AA comprising 56%. We classified 23 subjects with TBD independently of TL, only one of whom had severe AA (SAA) at initial presentation. Granulocyte numbers were insufficient for TL analysis in 28% of subjects, precluding a rigorous assessment of the impact of granulocyte TL on identification of TBD. Very low TL in lymphocytes or ≥3 lymphocyte subsets identified all TBD cases across AA severity. However, positive predictive value (PPV) was low, particularly in SAA. The detailed test had greater specificity and PPV, particularly in mild AA, which had the greatest proportion of TBD cases among those with AA, supporting its use. However, additional diagnostics, such as genetic testing, remain necessary in many cases to confirm TBD and avoid misclassification.