EHA 2026 | Predicting CNS relapse in ALL: integrating genetic and clinical risk factors
Anthony Moorman, PhD, Newcastle University, Newcastle, UK, discusses emerging approaches to predicting CNS relapse in acute lymphoblastic leukemia (ALL). Prof. Moorman reviews findings from analyses of consecutive UK clinical trials that identified genetic and clinical risk factors associated with CNS relapse, including age and white cell count. He explains how improved risk models may help optimize CNS-directed therapy in the era of blinatumomab. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
So that’s a really important point about CNS relapse. So CNS relapse back, you know, if you go back 30, 40 years, was a major problem. And when you had the introduction of intrathecal therapy, the risk of CNS relapse dropped dramatically and became much less important numerically than bone marrow relapse. But with the advent of blinatumumab, the risk of bone marrow relapse is decreasing because, of course, that’s where the action takes place...
So that’s a really important point about CNS relapse. So CNS relapse back, you know, if you go back 30, 40 years, was a major problem. And when you had the introduction of intrathecal therapy, the risk of CNS relapse dropped dramatically and became much less important numerically than bone marrow relapse. But with the advent of blinatumumab, the risk of bone marrow relapse is decreasing because, of course, that’s where the action takes place. But, of course, blinatumumab doesn’t cross the blood-brain barrier, so it doesn’t decrease your risk of CNS relapse. So one of the challenges facing clinical or protocol designers is how much therapy do you give to prevent CNS relapse in the Blinatumumab era. And what we were able to do is look at two consecutive trials in the UK to identify risk factors that were specific for CNS relapse. Now, some of those risk factors are also risk factors for bone marrow relapse, and that’s not necessarily a major surprise. But what we were able to do is develop a model that is based on genetics, age, white cell count, that can accurately predict patients who are at a very high risk of CNS relapse. And this is a CNS relapse of about 15% at five years, which is very high. And also a group of patients who have a very low risk of relapse, like less than 1%. So that kind of model may help clinicians design treatment protocols with blinatumumab and the appropriate amount of CNS-directed therapy.
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