Thyroid dysfunction in patients undergoing allogeneic stem cell transplantation in childhood and adolescence, thirty years follow-up
Authors:
P. Keslová 1; M. Šnajderová 2; R. Formánková 1; P. Říha 1; K. Personová 3; P. Sýkorová 3; B. Malinová 4; J. Starý 1; P. Sedláček 1
Authors‘ workplace:
Klinika dětské hematologie a onkologie FN Motol a 2. LF UK, Praha
1; Pediatrická klinika FN Motol a 2. LF UK, Praha
2; Klinika nukleární medicíny a endokrinologie FN Motol a 2. LF UK, Praha
3; Onkologická klinika FN Motol a 2. LF UK, Praha
4
Published in:
Čes-slov Pediat 2021; 76 (2): 99-107.
Category:
Original Papers
Overview
Radiotherapy and high-dose chemotherapy can cause a lot of early and late effects. Thyroid dysfunction is a known late complication following HSCT (hematopoietic stem cell transplantation). The objective of this study was to analyze the occurrence and characteristics of thyroid dysfunction in patients who have undergone HSCT in childhood and adolescence at our center (HSCT Unit, Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague).
Patients and methods: A retrospective review of clinical records was conducted for patients who had undergone allogeneic HSCT in childhood and adolescence, and subsequently were diagnosed with thyroid involvement. Thyroid gland function was evaluated in regular terms (pre-HSCT, six months, one year and then annually after HSCT). Ultrasound examination was performed in patients with thyroid gland involvement and as a screening. We have evaluated data in 463 patients (295 male, 168 female) who underwent allogeneic transplantation at a median age of 7.8 years (range: 0.1–20.5) from 1989 till 2018 and were alive more than one year after transplantation at the time of evaluation. Three hundred one patient (65%) were treated for malignant disease. In one‑third of patients who underwent HSCT, total body irradiation (TBI) conditioning regimen was used, almost 50% of patients underwent Busulphan based condition regimen. Three hundred twenty-seven transplantations (66.6%) were performed from an unrelated donor, 33.4% from a matched sibling or other family donor.
Results: One hundred sixty-nine patients (36.5%) were diagnosed with thyroid gland involvement at a median of 2.0 (range: 0.4–21.3) years after HSCT. Primary hypothyroidism was the most common type of thyroid dysfunction (110 patients – 65.1%), only nine of them were with clinical signs. Thyroid anti-bodies (aTPO, aTG) were detected in 95 patients. Thyroid nodules were found during ultrasound examination in 29 patients at a median of 11.5 (range 5.1–23.4) years after HSCT, fifteen patients were treated due to thyroid dysfunction (hypo = 8, AITD = 7). Thyroid carcinoma was diagnosed in 8 patients (in 1.7% of all patients, 27.6% of patients with nodules) at a median of 10.8 (range 5.4–21.5) years after HSCT. All but one had received TBI based conditioning regimen.
Conclusions: Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for a variety of malignant and non-malignant disorders. With the improved outcome, increasing attention has been drawn to late complications in long-term survivors. Thyroid dysfunction is one of the most frequent complications. Regular evaluation of thyroid gland function (every 6–12 months) including laboratory parameters is highly recommended. The risk of secondary malignancies after HSCT is increasing within time. Careful follow-up of thyroid status including annual ultrasound examination every 1–3 years, is very important for early detection of tumor, namely in all patients exposed to TBI.
Keywords:
thyroid dysfunction – hematopoietic stem cell transplant – childhood – thyroid carcinoma – follow-up care
Sources
1. Cetkovský P, Mayer J, Starý J, et al. Transplantace kostní dřeně a periferních hematopoetických buněk. 1. vydání. Praha: Galén, 2016: 1–413.
2. Keslová P. Sledování pacientů po léčbě hematologických malignit v dětském věku, pozdní následky léčby. Postgrad Med 2013;15 (5): 489–492.
3. Passweg JR, Baldomero H, Bader P, et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40000 transplants annually. Bone Marrow Transplant 2016; 51: 786–792.
4. Majhail NS. Long-term complications after hematopoietic cell transplantation. Hematol Oncol Stem Cell Ther 2017; 10 (4): 220–227.
5. Wingard JR, Vogelsang GB, Deeg HJ. Stem cell transplantation: Supportive care and long-term complications. Hematology. Am Soc Hematol Educ Program. 2002; 422–444. doi: 10.1182/asheducation-2002.1.422. PMID: 12446435 Review.
6. Roziakova L, Mladosievicova B. Endocrine late effects after hematopoietic stem cell transplantation. Oncol Res 2010; 18 (11–12): 607–615.
7. Dvorak CHC, Gracia CR, Sanders JE, et al. NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Endocrine Challenges-Thyroid dysfunction, Growth Impairment, Bone Health, Reproductive Risk. Biol Blood Marrow Transplant 2011; 17: 1725–1738.
8. Savani BN, Griffith ML, Jagasia S, et al. How I treat late effects in adults after allogeneic stem cell transplantation. Blood March 2011; 117 (11): 3002–3010.
9. Sanders JE, Hoffmeister PA, Woolfrey AE, et al. Thyroid dysfunction following hematopoietic cell transplantation in children: 30 years‘ experience. Blood 2009;113 (2): 306–308.
10. Al Taji E. Autoimunitní onemocnění štítné žlázy v ordinaci PLDD. Pediatr praxi 2018; 19(1): 13–17.
11. Al Taji E, Hnikova O. Tyreopatie v dětství a adolescenci. Pediatr praxi 2014;15 (3): 134–137.
12. Tauchmanova L, Selleri C, Rosa GD, et al. High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases. Cancer 2002; 95: 1076–1084.
13. Isshiki Y, Ono K, Shono K, et al. Autoimmune thyroid dysfunction after allogeneic hematopoietic stem cell transplant. Leukemia Lymphoma 2016; 57 (5): 1227–1229.
14. Ferry C, Gemayel G, Rocha V, et al. Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies. Bone Marrow Transplant 2007; 40: 219–224.
15. Savani B, Koklanaris E, Le Q, et al. Prolonged chronic graft-versus-host disease is a risk factor for thyroid failure in long-term survivors after matched sibling donor stem cell transplantation for hematological malignancies. Biol Blood Marrow Transplant 2009; 15: 377–381.
16. Jung YJ, Jeon YJ, Cho WK, et al. Risk factors for short term thyroid dysfunction after hematopoietic stem cell transplantation. Korean J Pediatr 2013; 56 (7): 298–303.
17. Hematological malignancies. Biol Blood Marrow Transplant 2009;.15: 377–381.
18. Cohen A, Rovelli A, van Lint MT, et al. Secondary thyroid carcinoma after allogeneic bone marrow transplant during childhood. Bone Marrow Transplant 2001; 28: 1125–1128.
19. Keslova P, Formankova R, Riha P, et al. Total body irradiation is a crucial risk factor for developing secondary carcinomas after allogeneic hematopoietic stem cell transplantation in childhood. Neoplasma accepted, ahead of print manuscript, cite article as https ://doi.org/10.4149/neo_2020_200214N131.
20. Vivanco M, Dalle JH, Alberti C, et al. Malignant and benign thyroid nodules after total body irradiation preceding hematopoietic cell transplantation durin childhood. Eur J Endocrinol 2012; 167: 225–233.
21. Myers KC, Howell JC, Wallace G, et al. Poor growth, thyroid dysfunction and vitamin D deficiency remain prevalent despite reduced intensity chemotherapy for hematopoietic sten cell transplantation in children and young adults. Bone Marrow Transplant 2016; 51 (7): 980–984.
Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2021 Issue 2
Most read in this issue
- Dysthymia as a less known form of depression: clinical picture and treatment
- Substance and non-substance addictions in adolescence
- Hantavirus hemorrhagic fever with renal syndrome – first pediatric cases in Slovakia
- Dorostové lékařství