IntroductionThyroid dysfunction has been reported after hematopoietic cell transplantation (HCT). 1-5 Radiation has been considered the main cause for this and for thyroid malignancies, but in the context of HCT total body irradiation (TBI) has been considered to be the major cause. Relatively little to no thyroid dysfunction has been reported after chemotherapy only preparative regimens for malignancies or severe aplastic anemia. 6-8 We have previously described hypothyroidism and compensated hypothyroidism after HCT. 1,6 Most studies of thyroid dysfunction after HCT have had relatively short follow-up of 1 to 6 years, but none have shown the various types of thyroid dysfunction that may occur nor described the trajectory of dysfunction over long periods of time. Here we report our experience with thyroid dysfunction and thyroid malignancies over a 30-year period. Results showed that thyroid dysfunction continued to develop for up to 28 years after HCT and that patients receiving busulfan-based regimens have thyroid dysfunction not significantly different from those given TBI-based regimens and significantly greater than regimens containing only cyclophosphamide. Methods PatientsWe investigated 791 patients who underwent their HCT at the Fred Hutchinson Cancer Research Center (FHCRC) between 1969 and December 31, 2006, were less than 18 years old at HCT, and survived for more than 1 year after HCT. Thyroid function was one of the endocrine systems evaluated in the study of the endocrine function of all pediatric patients. Data collected prospectively according to FHCRC Institutional Review Board-approved protocols 245 and 999 were reviewed. Patients were considered evaluable if they had either thyroid-stimulating hormone (TSH) and T 4 or T 3 or free T 4 testing performed. The study was approved by the Institutional Review Board and informed consent was obtained from the patients' parents in accordance with the Declaration of Helsinki. Patients included were a median of 9.5 years of age (range, 0.3-17.9) at HCT.

Growth impairment and growth hormone (GH) deficiency are complications after total body irradiation (TBI) and hematopoietic cell transplantation (HCT). To determine the impact of GH therapy on growth, the final heights of 90 GH-deficient children who underwent fractionated TBI and HCT for malignancy were evaluated. Changes in height standard deviation (SD) from the diagnosis of GH deficiency to the achievement of final height were compared among 42 who did and 48 who did not receive GH therapy. At HCT, GHtreated patients were younger (P ‫؍‬ .001), more likely to have undergone central nervous system irradiation (P ‫؍‬ .007), and shorter (P ‫؍‬ .005) than patients who did not receive GH therapy. After HCT, GH deficiency was diagnosed at 1.5 years (range, 0.8-9.5 years) for GH-treated and 1.2 years (range, 0.9-8.8 years) for nontreated patients. GH therapy was associated with significantly improved final height in children younger than 10 years at HCT (P ‫؍‬ .0001), but GH therapy did not impact the growth of older children.

Survivors of childhood acute lymphoblastic leukemia (ALL) may face an increased risk of metabolic and cardiovascular late effects. In order to determine the prevalence of and risk factors for adverse cardiometabolic traits in a contemporary cohort of pediatric ALL survivors, we recruited 48 off-therapy patients in remission treated with conventional chemotherapy and 26 treated with total body irradiation (TBI) based hematopoietic cell transplantation (HCT) in this cross-sectional pilot study. At a median age of 15 (range 8–21 years), HCT survivors were significantly more likely than non-HCT survivors to manifest multiple cardiometabolic traits including central adiposity, hypertension, insulin resistance, and dyslipidemia. Overall, 23.1% of HCT survivors met criteria for metabolic syndrome (≥3 traits) compared with 4.2% of non-HCT survivors (p=0.02). HCT survivors also had increased C-reactive protein and leptin levels and decreased adiponectin, suggestive of underlying inflammation and increased visceral fat. In multivariate analyses, history of HCT remained associated with ≥2 (OR 5.13, 95% CI 1.54, 17.15) as well as ≥3 (OR 16.72, 95% CI 1.66, 168.80) traits. Other risk factors included any cranial radiation exposure and family history of cardiometabolic disease. In summary, pediatric ALL survivors exposed to TBI-based HCT as well as any cranial radiation may manifest cardiometabolic traits at an early age and should be screened accordingly.

The role of transplantation in infants with acute lymphoblastic leukemia (ALL) is not defined. We analyzed results of 40 infants diagnosed before age 12 months who received a hematopoietic cell transplant (HCT) between July 1982 and February 2003 in first complete remission (CR1; n ‫؍‬ 17), CR2/3 (n ‫؍‬ 7), or relapse (n ‫؍‬ 16). Patients were conditioned with cyclophosphamide with total body irradiation (n ‫؍‬ 39) or busulfan (n ‫؍‬ 1). Donors were matched related (n ‫؍‬ 8), mismatched related (n ‫؍‬ 16), or unrelated (n ‫؍‬ 16). Graft-versus-host disease (GVHD) prophylaxis was methotrexate or cyclosporine (n ‫؍‬ 7) or methotrexate plus cyclosporine (n ‫؍‬ 33). Thirty-nine patients engrafted, 20 developed acute GVHD, and 7 developed chronic GVHD. Sixteen patients relapsed and 7 died of other causes. Patients in CR1 had disease-free survival (DFS) of 76% compared with 45% for CR2/CR3 and 8% for relapse (P < .001