06 March 2019

Researchers have announced a new test which they claim can identify chronic lymphocytic leukaemia (CLL) patients at higher risk of relapse more accurately than existing predictive markers.

The test is based upon measuring the length of telomeres – sections of DNA at the end of chromosomes in cells. Once telomeres have been worn away from repeated cell division, the chromosome ends are exposed and can suffer extensive DNA damage which increases the progression of cancer. The research team at Cardiff University have previously shown that telomere length is a critical indicator of potential cancer progression.

In the current research published in the journal Leukemia, the scientists at Cardiff University have developed a high-throughput test called ‘HT‑STELA’ to measure the length of telomeres. The team found that a short telomere length at diagnosis is linked to fast-progressing cancer, based on an analysis of samples from 260 patients enrolled in two clinical trials.

This group of patients who had shorter telomeres relapsed much sooner – by about two years on average – than did patients with long telomeres, after treatment with fludarabine, cyclophosphamide and rituximab (FCR)-based regimes. Overall survival was also significantly shorter in patients with shorter telomeres.

The team found that HT‑STELA was a more accurate predictor of relapse than testing for mutations in the IGHV gene, or other biomarkers such as β2 microglobulin expression, lymphocyte count, or CD38 expression. What’s more, the new version of the HT-STELA test is fast and could be used to guide doctors’ decisions on which drugs to give, say the researchers.

Professor Duncan Baird, who developed the test with Professors Chris Pepper and Chris Fegan, states: “Not all patients benefit equally from chemotherapy and this test is the only one available that can accurately predict how patients are likely to respond.

“Our research provides strong evidence that a significant number of patients should be receiving more appropriate treatments.”

The research was funded by the charity Bloodwise. Dr Alasdair Rankin, Director of Research at Bloodwise said: “People with chronic lymphocytic leukaemia can experience great anxiety and uncertainty about how their cancer will progress. This test could give people the peace of mind that they will receive the most effective treatment possible if it does.

“It may even allow some people to be told that their cancer is unlikely to progress.”

Source: Norris, K., Hillmen, P., Rawstron, A., Hills, R., Baird, D.M., Fegan, C.D., Pepper, C. (2019) “Telomere length predicts for outcome to FCR chemotherapy in CLL”, Leukemia, available from doi: 10.1038/s41375-019-0389-9


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