Thyroid Complications After Hemopoietic Stem Cell Transplantation in Children and Adolescents

Overview

Journal Hormones (Athens)

Specialty Endocrinology

Date 2024 Jul 14

PMID 39004683

Authors

Anatoli Fotiadou

Anna Paisiou

Eugenios Goussetis

Maria Kafetzi

Vilelmini Karayanni

Ioulia Peristeri

Elpis Athina Vlachopapadopoulou

Affiliations

Soon will be listed here.

Abstract

Purpose: To evaluate the prevalence of thyroid dysfunction and its association with possible contributing factors related to diagnosis and treatment in children who received hematopoietic stem cell transplantation (HSCT) in the only national transplant unit in Greece.

Methods: This is an observational, retrospective, single center cohort study that included 194 patients (58.6% boys) who survived for at least 1 year following allogeneic HSCT. Conditioning regimens depended upon diagnosis and protocols active at the time of transplantation. Some patients received irradiation, either central nervous system prophylaxis (n = 20), or total body irradiation (TBI) (n = 8). Thyroid gland evaluation included thyroid-stimulating hormone, free thyroxine, thyroid autoantibodies, and sonogram. Univariate and multivariate logistic models were used to examine the association of the above-mentioned factors with hypothyroidism.

Results: The mean age at diagnosis and at bone marrow transplant (BMT) in years was 7.51 ± 0.46 and 7.58 ± 0.36, respectively. The median follow-up time was 4.83 years. Hypothyroidism was detected in 33 cases (17.7%), four of those patients having received TBI. Factors contributing to hypothyroidism as per the multivariate analysis were male sex, [OR: 3.005, 95% CI (1.145-7.890)], irradiation, [OR: 2.876, 95% CI (1.120-7.386)], and years after HSCT [OR: 1.148, 95% CI (1.042-1.266)], while malignancy was identified only in the univariate analysis. The multivariate model presents a good class separation capacity [AUC = 72%, 95% CI (61.4%-82.4%)], Two patients had papillary thyroid cancer, both among children who had received TBI.

Conclusion: These data highlight the fact that male sex and radiotherapy are two independent factors that lead to increased risk for hypothyroidism. Furthermore, the prevalence of hypothyroidism increases with time post HSCT.

References

Wei C, Albanese A . Endocrine Disorders in Childhood Cancer Survivors Treated with Haemopoietic Stem Cell Transplantation. Children (Basel). 2016; 1(1):48-62. PMC: 4939518. DOI: 10.3390/children1010048. View

Passweg J, Baldomero H, Chabannon C, Basak G, de la Camara R, Corbacioglu S . Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021; 56(7):1651-1664. PMC: 8263343. DOI: 10.1038/s41409-021-01227-8. View

Khandelwal P, Millard H, Thiel E, Abdel-Azim H, Abraham A, Auletta J . Hematopoietic Stem Cell Transplantation Activity in Pediatric Cancer between 2008 and 2014 in the United States: A Center for International Blood and Marrow Transplant Research Report. Biol Blood Marrow Transplant. 2017; 23(8):1342-1349. PMC: 5669065. DOI: 10.1016/j.bbmt.2017.04.018. View

Sklar C, Antal Z, Chemaitilly W, Cohen L, Follin C, Meacham L . Hypothalamic-Pituitary and Growth Disorders in Survivors of Childhood Cancer: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103(8):2761-2784. DOI: 10.1210/jc.2018-01175. View

Rose S, Horne V, Howell J, Lawson S, Rutter M, Trotman G . Late endocrine effects of childhood cancer. Nat Rev Endocrinol. 2016; 12(6):319-36. DOI: 10.1038/nrendo.2016.45. View

Gebauer J, Higham C, Langer T, Denzer C, Brabant G . Long-Term Endocrine and Metabolic Consequences of Cancer Treatment: A Systematic Review. Endocr Rev. 2018; 40(3):711-767. DOI: 10.1210/er.2018-00092. View

de Kloet L, Bense J, van der Stoep M, Louwerens M, von Asmuth E, Lankester A . Late endocrine effects after hematopoietic stem cell transplantation in children with nonmalignant diseases. Bone Marrow Transplant. 2022; 57(10):1564-1572. DOI: 10.1038/s41409-022-01755-x. View

Leroy C, Cortet-Rudelli C, Desailloud R . [Endocrine consequences in young adult survivors of childhood cancer treatment]. Ann Endocrinol (Paris). 2016; 76(6 Suppl 1):S29-38. DOI: 10.1016/S0003-4266(16)30005-1. View

Dvorak C, Gracia C, Sanders J, Cheng E, Baker K, Pulsipher M . NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: endocrine challenges-thyroid dysfunction, growth impairment, bone health, & reproductive risks. Biol Blood Marrow Transplant. 2011; 17(12):1725-38. PMC: 3220735. DOI: 10.1016/j.bbmt.2011.10.006. View

10.

Sanders J, Hoffmeister P, Woolfrey A, Carpenter P, Storer B, Storb R . Thyroid function following hematopoietic cell transplantation in children: 30 years' experience. Blood. 2008; 113(2):306-8. PMC: 2615647. DOI: 10.1182/blood-2008-08-173005. View

11.

Majhail N, Rizzo J, Lee S, Aljurf M, Atsuta Y, Bonfim C . Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011; 18(3):348-71. PMC: 3279570. DOI: 10.1016/j.bbmt.2011.12.519. View

12.

Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V . Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009; 15(12):1628-33. PMC: 2861656. DOI: 10.1016/j.bbmt.2009.07.004. View

13.

Cibas E, Ali S . The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017; 27(11):1341-1346. DOI: 10.1089/thy.2017.0500. View

14.

Rivas A, Larumbe-Zabala E, Diaz-Trastoy O, Schurr R, Jones C, Abdulrahman R . Effect of chemoradiation on the size of the thyroid gland. Proc (Bayl Univ Med Cent). 2020; 33(4):541-545. PMC: 7549936. DOI: 10.1080/08998280.2020.1786227. View

15.

Myers K, Howell J, Wallace G, Dandoy C, El-Bietar J, Lane A . Poor growth, thyroid dysfunction and vitamin D deficiency remain prevalent despite reduced intensity chemotherapy for hematopoietic stem cell transplantation in children and young adults. Bone Marrow Transplant. 2016; 51(7):980-4. PMC: 4935546. DOI: 10.1038/bmt.2016.39. View

16.

van Beek R, van den Heuvel-Eibrink M, Hakvoort-Cammel F, van den Bos C, van der Pal H, Krenning E . Bone mineral density, growth, and thyroid function in long-term survivors of pediatric Hodgkin's lymphoma treated with chemotherapy only. J Clin Endocrinol Metab. 2009; 94(6):1904-9. DOI: 10.1210/jc.2008-0622. View

17.

Curtillet C, Cuadras P, Dore E, Chambost H, Thuret I, Michel G . [Thyroid dysfunction after haematopoietic stem cell transplantation during childhood]. Arch Pediatr. 2004; 11(11):1326-32. DOI: 10.1016/j.arcped.2004.07.017. View

18.

Ishiguro H, Yasuda Y, Tomita Y, Shinagawa T, Shimizu T, Morimoto T . Long-term follow-up of thyroid function in patients who received bone marrow transplantation during childhood and adolescence. J Clin Endocrinol Metab. 2004; 89(12):5981-6. DOI: 10.1210/jc.2004-0836. View

19.

Buxbaum N, Pavletic S . Autoimmunity Following Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2020; 11:2017. PMC: 7479824. DOI: 10.3389/fimmu.2020.02017. View

20.

Muller I, Moran C, Lecumberri B, Decallonne B, Robertson N, Jones J . 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy. Eur Thyroid J. 2019; 8(4):173-185. PMC: 6738237. DOI: 10.1159/000500881. View