To Lighten the Burden of Cure: Thyroid Disease in Long-Term Survivors After TBI Conditioning for Paediatric ALL.

Natalia Zubarovskaya,Dorothea Bauer,Ulrike Poetschger,Zoya Kuzmina,Carina Lender,Leila Ronceray,Anita Lawitschka,Paulina Kurzmann

doi:10.3389/fped.2021.798974

Natalia Zubarovskaya, Dorothea Bauer + Show 6 more

Open Access

https://doi.org/10.3389/fped.2021.798974

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Abstract

Thyroid disorders are well-studied after allogeneic haematopoietic stem cell transplantation (HSCT) following total body irradiation (TBI)-based conditioning, occurring in 15–30% of paediatric survivors. The toxic effect of TBI is known but data on the role of immunological dysregulation (ID) and chronic graft-versus-host-disease (cGvHD) are scarce. We studied functional and structural thyroid disorders in 97 paediatric ALL patients after TBI-based HSCT, assessing their correlation with patient/transplant characteristics including cGvHD, prolonged immunosuppression and ID. The 10- and 15-year cumulative incidence (CI) of functional disorders was 50 and 60%. Univariate analysis revealed TBI in 6 vs. 8 fractions (p = 0.01), an interval between ALL diagnosis and HSCT <1 year (p = 0.038), and the application of ATG (p = 0.044) as risk factors. The 10- and 15-year CI of structural disorders was 60 and 80%. No correlation between patient/transplant characteristics and structural disorders was observed. cGvHD, prolonged immunosuppression and additional radiotherapy were not associated with any thyroid disease. We observed a significant correlation between ID and the development of thyroid dysfunction in patients with structural changes (10-year CI: 77% for patients with ID vs. 56% without ID, p = 0.02). The impact of our results on thyroid follow-up evaluations and the significance of hormonal replacement therapy are discussed.

Highlights

The endocrine system is commonly affected by high-dose chemotherapy and/or irradiation given prior to allogeneic haematopoietic stem cell transplantation (HSCT) during childhood
Thyroid disorders after paediatric HSCT using total body irradiation (TBI)-based conditioning have been well-studied over the last decade [2]
In this present retrospective study on a homogenous cohort of paediatric patients with acute lymphoblastic leukaemia (ALL) following TBI-based HSCT, we investigated the incidence of both functional and structural thyroid disorders and the association between these and graft-versus-host disease (GvHD), prolonged immunosuppressive treatment and humoral immune dysregulation to gain insight into possible immune-mediated damage to the thyroid gland

Summary

Introduction

The endocrine system is commonly affected by high-dose chemotherapy and/or irradiation given prior to allogeneic haematopoietic stem cell transplantation (HSCT) during childhood. Thyroid failure after total body irradiation (TBI) as conditioning for paediatric HSCT is well-studied [1, 2]. To reduce transplant-related toxicity, an aim of clinical research in the field of paediatric HSCT has been replacement of TBI with chemoconditioning. Thyroid Disease After TBI in Paediatric ALL significantly higher 2-year event-free survival in paediatric patients with acute lymphoblastic leukaemia (ALL) receiving HSCT after TBI-based conditioning vs after chemoconditioning [6]. Hypothyroidism is usually a relatively early complication after HSCT but it can manifest at any time point, with an increasing incidence during follow-up [2]. The most common functional thyroid disorders after HSCT include compensated and overt hypothyroidism as well as immune thyroiditis. The reported incidence of hypothyroidism varies depending on the duration of follow-up, ranging from 15 to 30% for compensated hypothyroidism and from 10 to 15% for overt hypothyroidism. The incidence of immune thyroiditis has been reported to be much lower, at 0.5% [1,2,3]

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