Short telomeres in ILD not impacting transplant outcomes


By Mardi Chapman

26 Mar 2024

Dr Yai-Ling Zhang

Telomere length does not appear to impact outcomes in patients undergoing lung transplantation for fibrosing lung disease, the TSANZSRS 2024 meeting has heard.

Dr Lai-Yung Zhang presented a retrospective study of all 52 lung transplant recipients at the Queensland Lung Transplant Service who had their peripheral blood telomere length measured via Flow-FISH and had undergone transplantation for a fibrosing lung disease.

The study found 31 patients (59.6%) had a short telomere length defined as ≤10th centile and generally associated with younger onset, more severe lung disease, faster progression and extra pulmonary features.

Short-telomere recipients were demographically similar to normal-telomere recipients, with no statistically significant difference in age at time of transplant, gender, or underlying pre-transplant ILD diagnosis.

As well, short telomere length compared to normal telomere length did not appear to impact post-transplant bone marrow suppression and overall CLAD-free survival.

Short telomere length was not found to be associated with shorter time to any cytopenia, shorter time to clinically significant neutropenia, or cytomegalovirus viremia.

Dr Zhang, from the Prince Charles Hospital, told the limbic that while telomere length was not statistically associated with duration of cytopenia or duration of significant neutropenia post-transplant, there was a trend towards significance.

“So the number of days it takes for the patients to become cytopenic were quite similar across both groups, but the duration of cytopenia was very close to being significantly higher in the short telomere patients.”

“That being said, I think in this cohort of patients, the cytopenia that we most worry about is neutropenia … and interestingly, when you actually drill down into neutropenia alone, the time to first neutropenia was non significant, but there was a trend towards it being earlier in the normal telomere length patients rather than short telomere which is really interesting and not expected.”

“And the duration of clinically significant neutropenia requiring G-CSF administration, etc. was actually very clearly similar across both groups.”

No significant difference in time to chronic lung allograft dysfunction (CLAD) or death was found in short-telomere recipients compared to recipients with normal telomere length.

Reassuring results

Dr Zhang said the results were both surprising and somewhat reassuring.

“I think one of our big concerns in lung transplant with these particular patients is not necessarily the lung disease, because their lungs get transplanted, but their extra pulmonary features. So one of the main things that people worry about is their bone marrow suppression.”

“And the concern really is that if these short telomere patients already have a predisposition to bone marrow suppression, will that worsen their outcomes on immunosuppression? Because if their counts become quite low, then we have to withdraw immunosuppression and then theoretically increase rates of rejection, etc.”

Dr Zhang said the evidence from other cohorts was inconsistent.

“It’s always very difficult to compare obviously with different cohorts from different centres, and different practices in terms of induction and immunosuppression.”

“…but it is quite important to know because we’re now starting to realise that, as we do this testing more and more, we’re actually finding that a reasonable proportion of our ILD patients who undergo lung transplant do have short telomeres,” she said.

Dr Zhang said a larger, multicentre prospective study was required to clarify the findings.

Meanwhile, telomere length was still not a routine test, she said.

“But generally what we do is in specialised ILD centres if we are clinically suspicious of a telomere syndrome – so if they’ve gone grey in their early 20s, if they’re still quite young, if there’s any family history of interstitial lung disease, or if there’s any cirrhosis or bone marrow suppression in the family – then we send them off for telomere length testing and that helps give us more information about the progress of their lung disease.”

Similarly, genetic testing can be useful in certain situations, according to Dr Zhang.

“But it doesn’t always provide you with that much more information, the reason being that we know that the mutations that can cause telomere disorders don’t have complete penetrance and also because we’ve only just started investigating genetic disorders in this field. There are a lot of variants of unclear significance.”

“Generally …  if there’s a family history of ILD, you would test genetics. But if there’s just an isolated case and you’re suspicious of a short telomere condition but there’s not a lot of family history, there may not be much utility to doing genetic tests,” she concluded.

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