Thalassaemia syndromes: Case

Interpretation of the cardiac and endocrine findings

The cardiac T2 star of 8 milliseconds marks severe myocardial iron loading and a high short-term risk of heart failure, the leading cause of death in thalassaemia major. A value of over 20 milliseconds is normal, and a value under 10 milliseconds is the threshold for severe loading, so this boy is in the high-risk band. The impaired glucose tolerance and the short stature with delayed puberty are the endocrine consequences of iron loading of the pancreas and the anterior pituitary, and they confirm that the deferasirox alone is not controlling the iron. The high ferritin and liver iron show a total body iron load that is out of control, and the picture is one of a child at risk of the very cardiac and endocrine complications the chelation programme is built to prevent. [8][11]

Change in management

The immediate change is the intensification of chelation to protect the heart. Deferiprone is the chelator with the strongest evidence for removing cardiac iron, so it is added to the deferasirox, or the regimen is switched to a combination of deferasirox and deferiprone, with the weekly absolute neutrophil count monitored for the risk of agranulocytosis. A short course of intensive intravenous deferoxamine is sometimes added for the most severe cardiac loading. The endocrine late effects need their own management: an endocrine review for the growth and pubertal axes with consideration of growth hormone and sex-steroid replacement, a repeat oral glucose tolerance test with early insulin or oral hypoglycaemic therapy for the glucose intolerance, and surveillance for diabetes, hypothyroidism and hypoparathyroidism. The adherence to chelation is explored directly, because the most common reason for uncontrolled iron is a lapse in the daily tablet. [7][11]

Counselling on the curative options

The family is counselled that the boy has a curative pathway open to him that would remove the lifelong transfusion and chelation burden. An allogeneic haematopoietic stem cell transplant from a matched sibling donor is the longest-established cure, with survival over 90 percent in the well-chelated, young child, and the siblings are tested for a match. Where no matched sibling is available, betibeglogene autotemcel gene therapy adds a functional beta-globin gene to the boy's own stem cells and produces durable transfusion independence, as the pioneer trial of Thompson and colleagues showed, but it carries the cost and the conditioning-related infertility. The cardiac T2 star is corrected before any curative conditioning is undertaken, and the curative decision is weighed against the burden and the long-term data as the boy moves towards transition. [1][12]