Analysis of iron status in paediatric acute lymphoblastic leukaemia

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Published: 6 May 2015
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Dr Charlotte Brierley - Royal Hospital for Sick Children, Edinburgh, UK

Dr Charlotte Brierley talks to ecancertv at BSH 2015 about iron status in paediatric acute lymphoblastic leukaemia.

Dr Brierley discusses recent studies involving a clinical cohort of children monitoring whether the transfusion burden they received during therapy had any long term implications, specifically focusing on the extent that the patients were affected by iron burden or iron overload.

Essentially we took a closer look at our clinical cohort of a group of children who were treated at the Royal Hospital for Sick Children here in Edinburgh and looked at the transfusion burden that they received during their therapy and tried to assess the extent to which they were affected by iron overload and what iron burden they received and to postulate what the clinical consequences of that might be in the longer term.

What were your findings?

In the first instance it’s very difficult to assess iron burden and iron toxicity in this cohort. The markers of iron burden that are used in adults or that are used in health, such as serum ferritin, are essentially unreliable. We tracked serum ferritin through the course of their therapy and it was high at the beginning of treatment before they’d had even any transfusions and remained high all the way throughout. So ferritin is essentially unreliable, is confounded by the degree of inflammation, the infections that these children encounter. But we did assess the transfusion burden and these children are transfused really very significantly with an average of 195ml/kg which is about 13 doses. That, in other studies, has been deemed to be sufficient to cause iron overload and that indeed was corroborated on their bone marrow aspirates which demonstrated that they really did have quite significant iron staining in remission. So overall the treatment of childhood ALL has had very good outcomes, survival has improved significantly but there is now a focus on reducing the morbidity associated with therapy. The toxicity profile from iron overload is very similar to the toxicity profile from chemotherapy and the mechanisms of late effects, post-chemotherapy, are quite poorly understood. But our theory is certainly that iron overload may be quite a significant contributor in long-term morbidity post-treatment in paediatric ALL survivors.

Were there any other secondary considerations you had to take into account when looking at the children?

Obviously these are children who have a very high treatment burden. That’s also reflected in the bone marrow assessments - a lot of these bone marrows were aparticulate and so about half of them actually couldn’t even be assessed for iron status. So that adds an extra degree of complexity when trying to look at iron status in this cohort. Essentially we need better markers of iron status, specifically in this context. There are some on the horizon but their clinical validity has yet to be proven, so markers such as erythroferrone or hepcidin may in future become important in the assessment of iron in this specific setting.

What’s next?

It would be very interesting for us to follow our cohort forward. It’s quite a small cohort but it’s select and we have a lot of patient demographic information on them. It would be interesting to see in the longer term what morbidity they experience and also, taking it further, whether we could look at assessing them using organ-specific methods of looking at iron burden in specific organs, so cardiac or liver MRI for example.

Do you believe this could change clinical practice?

It was a small cohort but the most important lesson, perhaps, to draw from it is that clinicians should be aware that this is a potential problem; that patients sometimes are very heavily transfused – one or two patients in our cohort had over fifty transfusions during their therapy, which is a very significant iron burden for a small person. While the long-term complications following this perhaps remain to be seen, I think there is an argument to say that some of these children will just simply grow up and use up their iron as they grow up. But equally it is an awareness of iron burden, knowing to assess on bone marrow, to stain bone marrow aspirates routinely for iron, and to consider further iron storage assessment, so using liver or cardiac MRI in patients where there is any concern of toxicity related to iron overload.