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The cost of cure

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Rachel was diagnosed with acute lymphoblastic leukaemia (ALL) at 6 years of age, and treated on the UKALL XI protocol 1 with randomisation to high dose methotrexate plus third intensification. She relapsed 22 months after the initial diagnosis and received further chemotherapy and a matched unrelated donor bone marrow transplant (BMT). Her conditioning for the BMT included cyclophosphamide and total body irradiation (TBI) (eight fractions of 180 cGy each). She developed graft versus host disease post-transplant and was treated with high dose methylprednisolone for five weeks and oral prednisolone for several weeks thereafter. One year after BMT she continued to be in remission from her leukaemia.

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  • Bone marrow transplant, especially when TBI is part of the conditioning regimen, is associated with both endocrine and non-endocrine co-morbidity (table1).2 Dividing the total dose of irradiation into smaller fractions (fractionation) is used to minimise these late effects of treatment. High dose corticosteroids, used to treat graft versus host disease, heighten the risk of iatrogenic adrenal suppression. Recovery of adrenal function usually occurs with time but this is not universal and steroid replacement therapy is sometimes needed. Therefore, after stopping steroid treatment the pituitary–adrenal axis should be assessed with a Synacthen test in all children treated with steroids for graft versus host disease, and replacement steroid therapy given if appropriate.

At 9 years of age Rachel is referred to the BMT follow up clinic for ongoing monitoring for evolving sequelae of treatment. It is now just over one year after her transplant. Routine blood tests taken as part of her annual review included thyroid function tests. The results were: free thyroxine (FT4) 8.8 pmol/l (normal range: 10.8–18.7 pmol/l); thyroid stimulating hormone (TSH) 12 mlu/l (normal range: 0.5–4.5 mlu/l).

Although Rachel has no clinical features of hypothyroidism, the abnormal thyroid function results come …

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