Secondary thyroid carcinoma after allogeneic bone marrow transplantation during childhood

Cohen, Amnon; Rovelli, Attilio; Lint, M. T. Van; Merlo, F.; Gaiero, Alberto; Mulas, R; Balduzzi, Adriana; Cortí, Paola; Uderzo, C; Bacigalupo, Andrea

doi:10.1038/sj.bmt.1703290

Cited by 44 publications

(21 citation statements)

References 20 publications

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“…treated with 1200 cGy. The other study focused on patients with thyroid carcinoma only, which was found in eight (7%) of the 113 patients investigated with a median of 8.5 years (range: 3.1-15.7) after TBI (24). This frequency was similar to the 8% reported here for thyroid carcinoma, with a similar follow-up period.…”

Section: Discussionsupporting

confidence: 61%

“…With the increasing use of ultrasound scans and FNAB, thyroid carcinoma tends to be diagnosed very accurately at early stages (51). Only two other retrospective studies reported the results of ultrasound examinations for the detection of thyroid nodules and/or carcinoma during the follow-up of patients receiving TBI as part of conditioning regimens for HSCT during childhood (22,24). One of these studies on 42 patients surviving for at least 10 years after TBI, in which earlier effects were not investigated, showed that nodules were present in 60% of the patients and that thyroid carcinoma occurred in six (25%) of the 24 patients with nodules after a median of 12 years of follow-up (22), consistent with the diagnosis of thyroid carcinoma for 29% of the nodules in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few studies have investigated survivors who received total body irradiation (TBI) for hematopoietic stem cell transplantation (HSCT). These studies included patients receiving various type of TBI according to various schedules, as a single dose or fractionated, with a total dose of 990-1200 cGy; some of these patients also received cranial radiation as a first-line treatment for various hematological and oncological diseases (22,23,24,25,26,27). Moreover, the method of screening differed between studies, with some studies using more sensitive methods than others.…”

Section: Introductionmentioning

confidence: 99%

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Malignant and benign thyroid nodules after total body irradiation preceding hematopoietic cell transplantation during childhood

Vivanco

Dalle²,

Alberti³

et al. 2012

European Journal of Endocrinology

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Background: The risk of radiation-induced benign and malignant thyroid nodules is well known. Objective: The aim of this study was to determine the occurrence of thyroid nodules and carcinomas after fractionated total body irradiation (TBI) preceding hematopoietic stem cell transplantation (HSCT) for malignant hematological disease during childhood. Methods: We conducted a retrospective university hospital-based observational study. The participants were 76 patients receiving fractionated TBI between 1989 and 2009 as part of the conditioning regimen for HSCT to treat malignant hematological disease, with a median age of 8.2 (5.7-11.4) years, for whom the last ultrasound examination was performed at a median age of 14.2 (11.2-17) years. The main outcome measure was cumulative incidence of thyroid nodules detected by ultrasound scans followed by biopsy if necessary. Results: Thyroid nodules were examined in 21 (28%) patients, six (29%) of whom were diagnosed with thyroid carcinoma at the age of 2.2-18.6 years after TBI. The cumulative incidence of nodule occurrence increased with increasing time from diagnosis. The 10-year cumulative incidence of benign and malignant thyroid nodules was 16% (95% confidence interval (CI) 4-27%) and 8% (95% CI 0-16%) respectively. Seventeen (22%) patients had hypothyroidism (compensated nZ12, in five patients it was transient). No significant independent risk factors were identified in the multivariable competing risk model as a function of nodule occurrence. Conclusion: Short-term and life-long monitoring, with screening for nodules of the thyroid gland using ultrasound scans, is recommended for survivors subjected to TBI for HSCT during childhood.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Malignant and benign thyroid nodules after total body irradiation preceding hematopoietic cell transplantation during childhood

Vivanco

Dalle²,

Alberti³

et al. 2012

European Journal of Endocrinology

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“…The cause of death was not specified. Cohen et al 12 reported that eight out of 113 patients developed thyroid cancer at a median of 10 years after BMT. Only one patient had a palpable nodule, but ultrasonography was performed annually.…”

Section: Discussionmentioning

confidence: 99%

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

Berger

Le-Gallo

Donadieu

et al. 2005

Bone Marrow Transplant

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Summary: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 ¼ 5) and surgery (n ¼ 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 ¼ 2) or CH (n ¼ 2). We concluded that children who undergo BMT for ALL are at a high risk of subsequent thyroid dysfunction. Bone Marrow Transplantation (2005) 35, 991-995.

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“…The intensive conditioning regimens required in most cases often result in impaired growth and reduced final height, especially if unfractionated TBI is part of the conditioning regimen (1). TBI can impair growth both directly, by damaging the epiphyseal growth plates, and indirectly, by decreasing GH secretion, or by causing hypogonadism or hypothyroidism (2).…”

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confidence: 99%

Patterns of Growth and Body Proportions After Total-Body Irradiation and Hematopoietic Stem Cell Transplantation During Childhood

et al. 2006

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Patterns of growth and body proportions were studied in 75 children receiving total-body irradiation (TBI) and hematopoietic stem cell transplantation (SCT) before onset of puberty. Of the 19 patients receiving GH, only data obtained before onset of GH were included. Thirty-two patients reached final height (FH). Median change in height SD score (SDS) between SCT and FH was -1.7 in boys and -1.1 in girls. Peak height velocity (PHV) was decreased in the majority of the patients (median PHV 5.7 cm/y in boys and 5.3 cm/y in girls), even though it occurred at appropriate ages. Changes in body proportions were analyzed by linear mixed-effects models. Decrease in sitting height SDS did not differ between boys and girls. In boys, decrease in leg length SDS was of comparable magnitude, whereas, in girls, decrease in leg length was less pronounced, leading to a significant decrease in SDS for sitting height/height ratio in girls only. The sex-specific effects of several variables on height SDS were analyzed by linear mixed-effects modeling, showing a slightly faster decrease in younger children and a more pronounced decrease during puberty in boys compared with girls. We conclude that 1) younger children are more susceptible to growth retardation after TBI and SCT, 2) pubertal growth is more compromised in boys, and 3) leg growth is relatively less affected in girls, possibly due to a high incidence of gonadal failure in girls. H ematopoietic SCT has become a standard treatment option for many children with congenital or malignant disorders of the hematological system. The intensive conditioning regimens required in most cases often result in impaired growth and reduced final height, especially if unfractionated TBI is part of the conditioning regimen (1). TBI can impair growth both directly, by damaging the epiphyseal growth plates, and indirectly, by decreasing GH secretion, or by causing hypogonadism or hypothyroidism (2). Other factors that may contribute to growth delay are chronic graftversus-host disease in recipients of allogeneic transplants, use of corticosteroids, psychosocial dysfunction, and insufficient nutritional intake.In contrast to the extensively documented negative effect of TBI and SCT on height, more recently completed with data on final height (1,3-8), the effect of TBI and SCT on other aspects of growth are less intensively studied. To our knowledge, for example, height development after TBI and SCT (including influences of sex and puberty) has not yet been modeled, and the effect on body proportions has been the subject of only a few studies (5,9 -12). Moreover, most of these studies included patients who had received cranial irradiation before TBI, patients who had already entered puberty at the time of SCT, or patients who had been treated with GH. In addition, none of these studies considered sex differences.In an attempt to clarify these aspects of growth after SCT, we investigated sex-specific development of height, body proportions, and final height in children receiving TBI and ...

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Secondary thyroid carcinoma after allogeneic bone marrow transplantation during childhood

Cited by 44 publications

References 20 publications

Malignant and benign thyroid nodules after total body irradiation preceding hematopoietic cell transplantation during childhood

Malignant and benign thyroid nodules after total body irradiation preceding hematopoietic cell transplantation during childhood

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

Patterns of Growth and Body Proportions After Total-Body Irradiation and Hematopoietic Stem Cell Transplantation During Childhood

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