General Updates | Examining the morbidity rate in adults with NTDT referred to US specialty centers

So, we performed an analysis of three thalassemia specialty centers between 2013 and 2023, and looked at all the adult patients with non-transfusion-dependent thalassemia, or NTDT, who were referred to our centers during this time. And what we observed was a very high rate of morbidities. And these really spanned all organ systems. So including, you know, a history of splenectomy, paraspinal masses, and also cardiovascular complications like pulmonary hypertension, arrhythmias, and also endocrine dysfunction as well, like low bone density, hypogonadism, and diabetes. And we also saw a substantial number of people who had a history of venous thromboembolism. Among our cohort, endocrine disorders were the most frequent, and of these, low bone density, so things like osteopenia, osteoporosis, accounted for almost 40% of patients who we observed in this cohort. 

And then furthermore, we also saw that a substantial number of these patients who were referred in adulthood had ongoing evidence of iron overload. So almost 40% of people who were first referred to our thalassemia centers in adulthood had a ferritin on presentation of over 800 nanograms per milliliter, and only about a quarter of them, fewer than a quarter were on iron chelation at the time of referral. There was a subset of these people who also underwent MRI assessment of iron overload looking at liver iron concentration as well as cardiac T2 star. And what we observed is that, of those people who underwent this MRI assessment, half of them had a liver iron content of over 5, but again, fewer than a quarter of those people were on iron chelation, despite their imaging evidence of iron overload. And then there were three patients among our cohort who were known to have a cardiac T2 star, less than 20 milliseconds, which indicates cardiac iron overload. And none of those patients were on iron chelation. And kind of looking at a different metric, about half of our patients, 49% of the patients with NTDT, ultimately were recommended to start regular transfusions after the initial consultation. 

So all this put together, we do see high rates of morbidities in this slice of the population that manifests in many different ways affecting many different organ systems, and many of which, you know, meet the criteria for initiation of regular transfusions. You know, I think this high rate of morbidities is particularly undernoticed in those people with non-transfusion-dependent thalassemia and really emphasize that NTDT is not a benign condition. And so I think this really moves the needle in terms of prompting us to investigate ways of better surveilling for morbidities related to chronic ineffective erythropoiesis and long-term complications related to iron overload and to thalassemia. And so I think there’s definitely room for improvement in terms of better understanding how to surveil these people for morbidities and really indicates to us that there’s a need for early referral to thalassemia specialty centers for people with non-transfusion-dependent thalassemia because the designation of non-transfusion-dependent may change over time. And as we see, half of these patients end up ultimately needing regular transfusions. And so NTDT may not be an accurate diagnosis for them for all their lives. This is a dynamic descriptor of thalassemia. And so people who start off their childhood and adolescence non-transfusion dependent may eventually meet criteria to start regular transfusions.

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