Late thyroid toxicity in 153 long-term survivors of allogeneic bone marrow transplantation for acute lymphoblastic leukaemia

Abstract

The purpose of this study was to identify risk factors for hypothyroidism after bone marrow transplantation (BMT) for high-risk or relapsed acute lymphoblastic leukaemia (ALL) in children. In all, 388 children with acute lymphoblastic leukaemia underwent allogeneic bone marrow transplantation between 1984 and 1994. Overall 5-year survival was 54.6%. Thyroid function was assessed in the 153 patients with more than 5 years of follow-up. In total, 16 patients developed uncompensated hypothyroidism (UH) and 46 compensated hypothyroidism (CH) a median of 2.9 and 2.7 years, respectively, after BMT. Thyroid dysfunction-free survival rates were 73.2% after 5 years and 59.2% after 10 years. Three factors were significantly associated with the onset of hypothyroidism, namely age, bone marrow transplantation in second remission, and single-dose total body irradiation (TBI). Ultrasonography of the thyroid showed nodules in 10 of 35 patients. The median time from BMT to nodule detection was 7.8 years. Cytology (n=5) and surgery (n=4) showed no evidence of thyroid cancer. Four of the 14 patients who received cytoreduction without TBI but with busulphan and cyclophosphamide developed UH (n=2) or CH (n=2). We concluded that children who undergo BMT for ALL are at a high risk of subsequent thyroid dysfunction.