Time-course and risk factors of hypothyroidism following allogeneic hematopoietic stem cell transplantation (HSCT) in children conditioned with fractionated total body irradiation

Background. Hypothyroidism is a complication of hematopoietic stem cell transplantation (HSCT)l that has been studied primarily in children after matched sibling bone marrow transplantation. Unrelated donors and umbilical cord blood (CB) are now used in transplantation, and hypothyroidism in these populations is undocumented. Children who underwent fractionated total body irradiation (fTBI) and received bone marrow or umbilical cord blood transplantation from siblings or unrelated donors were examined for hypothyroidism over time. Procedure. All children who received fTBI prior to allogeneic HSCT at The Children's Hospital (TCH), Denver between 1994 and 2002, and survived >1 year were included (N = 41 eligible; N = 33 met inclusion criteria). Probability of hypothyroidism was estimated by the Kaplan-Meier method and groups were compared using Cox's proportional hazards regression model. Results. Hypothyroidism developed in 52% of the children at a median time of 1.9 years (range 0.7-8.3 years). Primary compensated hypothyroidism was diagnosed in 94% of those affected. Children who received unrelated donor HSCT were 8.4 times more likely to develop hypothyroidism than those receiving matched sibling HSCT. Recipients of CB were 4.6 times more likely to have hypothyroidism than recipients of bone marrow. Conclusions. There is a significant risk of developing hypothyroidism following fTBI, and allogeneic HSCT, that appears greater in recipients of unrelated donor HSCT and CB transplantation. Most of our patients who received BMT had sibling donors and the majority of CB transplants were from unrelated donors. It is difficult to determine which association is related to hypothyroidism, but the combination is significant.