Thyroid dysfunction following bone marrow transplantation: long-term follow-up of 80 pediatric patients

Thyroid function was evaluated in children surviving disease-free for 2 years or more following bone marrow transplantation (BMT) for severe aplastic anemia (27 patients), acute non-lymphoblastic leukemia (28 patients), and acute lymphoblastic leukemia (25 patients). Pre-BMT conditioning consisted of high dose chemotherapy and total lymphoid irradiation with 750 cGy for patients with severe aplastic anemia, and for patients with leukemia, high dose chemotherapy and single dose total body irradiation with 750-850 cGy (33 patients) or fractionated total body irradiation with 1320 cGy (20 patients). Compensated hypothyroidism (elevated thyroid stimulating hormone (TSH) with a normal thyroxine index) occurred in 20/80 patients with a median time of onset of 12.3 months post-BMT (range 4-30). No patients developed primary hypothyroidism (elevated thyroid stimulating hormone with low thyroxine index). In seven patients, compensated hypothyroidism was transient with TSH returning to normal at a median of 60 months post-BMT (range 11-75). Six patients with compensated hypothyroidism received thyroid hormone replacement therapy. Time to development of compensated hypothyroidism was associated (p = 0.03) with underlying disease and radiation (11 of 27 patients with severe aplastic anemia + total lymphoid irradiation versus nine of 53 patients with leukemia + total body irradiation). In aplastic anemia patients, but not patients with leukemia, the incidence of thyroid hypofunction 5 years post-transplant was significantly higher (p less than 0.001) in those receiving methotrexate alone (82%) as prophylaxis for graft-versus-host disease compared with those receiving a regimen of methotrexate, antithymocyte globulin and prednisone (16%).