nach oben

Journal of Endocrinological Investigation

Erschienen in:

08.03.2023 | Original Article

Impact of allogeneic stem cell transplantation on thyroid function

verfasst von: F. Felicetti, F. Gatti, D. Faraci, D. Rosso, M. Zavattaro, N. Fortunati, L. Marinelli, S. Leone, J. Gill, M. Dionisi-Vici, C. Dellacasa, A. Busca, L. Giaccone, E. Arvat, B. Bruno, E. Brignardello

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 9/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Primary hypothyroidism is a main endocrine complication after allogeneic stem cells transplantation (allo-SCT) in children, but in adults data on post-SCT hypothyroidism are limited. The aims of this observational, cross-sectional study were to assess the prevalence of hypothyroidism in adult allo-SCT recipients according to time from transplantation, and to identify risk factors.

Methods

One hundred and eighty-six patients (M 104; F 82; median age 53.4 years) who underwent allo-SCT between January 2010 and December 2017 were enrolled and divided into three groups, according to time from allo-SCT (1–3 years; 3–5 years; > 5 years). Pre-transplant TSH and fT4 levels were available for all patients. After transplantation, TSH, fT4 and anti-thyroperoxidase antibodies (TPO-Ab) were evaluated.

Results

After a follow-up of 3.7 years, 34 (18.3%) patients developed hypothyroidism, with higher prevalence in females (p < 0.001) and in patients who received matched unrelated donor grafts (p < 0.05). No difference in prevalence was found at different time points. Patients who developed hypothyroidism showed higher rate of TPO-Ab positivity (p < 0.05) and higher pre-transplant TSH levels (median 2.34 µU/ml) compared to those with preserved thyroid function (median 1.53 µU/ml; p < 0.001). Multivariable analysis identified higher pre-transplant TSH levels as a positive predictor of hypothyroidism (p < 0.005). The ROC curve analysis identified a pre-SCT TSH cutoff of 1.84 µU/ml, which can predict hypothyroidism with sensitivity 74.1% and specificity 67.2%.

Conclusions

About one out of four patients developed hypothyroidism after allo-SCT, with a greater incidence in females. Pre-transplant TSH levels seem to predict the onset of post-SCT hypothyroidism.

Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, Gratwohl M, Bouzas LF, Confer D, Frauendorfer K, Gluckman E, Greinix H, Horowitz M, Iida M, Lipton J, Madrigal A, Mohty M, Noel L, Novitzky N, Nunez J, Oudshoorn M, Passweg J, van Rood J, Szer J, Blume K, Appelbaum FR, Kodera Y, Niederwieser D, Worldwide Network for Blood and Marrow Transplantation (WBMT) (2015) One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol 2(3):e91–100. https://doi.org/10.1016/S2352-3026(15)00028-9. [Erratum in: Lancet Haematol. 2015 May;2(5):e184. PMID: 26687803.Duell, T. Health and Functional Status of Long-Term Survivors of Bone Marrow Transplantation. Ann. Intern. Med. 126, 184 (1997)]

Duell T, van Lint MT, Ljungman P et al (1997) Health and functional status of long-term survivors of bone marrow transplantation. EBMT Working Party on Late Effects and EULEP Study Group on Late Effects. European Group for Blood and Marrow Transplantation. Ann Intern Med 126(3):184–192. https://doi.org/10.7326/0003-4819-126-3-199702010-00002CrossRefPubMed

Chiodi S, Spinelli S, Ravera G, Petti AR, Van Lint MT, Lamparelli T, Gualandi F, Occhini D, Mordini N, Berisso G, Bregante S, Frassoni F, Bacigalupo A (2000) Quality of life in 244 recipients of allogeneic bone marrow transplantation. Br J Haematol 110(3):614–619. https://doi.org/10.1046/j.1365-2141.2000.02053.xCrossRefPubMed

Lee SJ, Logan B, Westervelt P, Cutler C, Woolfrey A, Khan SP, Waller EK, Maziarz RT, Wu J, Shaw BE, Confer D, Horowitz MM, Anasetti C (2016) Comparison of patient-reported outcomes in 5-year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: long-term follow-up of a randomized clinical trial. JAMA Oncol 2(12):1583–1589. https://doi.org/10.1001/jamaoncol.2016.2520.PMID:27532508;PMCID:PMC5145732CrossRefPubMedPubMedCentral

Khera N, Storer B, Flowers ME, Carpenter PA, Inamoto Y, Sandmaier BM, Martin PJ, Lee SJ (2012) Nonmalignant late effects and compromised functional status in survivors of hematopoietic cell transplantation. J Clin Oncol 30(1):71–77. https://doi.org/10.1200/JCO.2011.38.4594CrossRefPubMed

Giaccone L, Felicetti F, Butera S, Faraci D, Cerrano M, Dionisi Vici M, Brunello L, Fortunati N, Brignardello E, Bruno B (2020) Optimal delivery of follow-up care after allogeneic hematopoietic stem-cell transplant: improving patient outcomes with a multidisciplinary approach. J Blood Med 15(11):141–162. https://doi.org/10.2147/JBM.S206027CrossRef

Zavattaro M, Felicetti F, Faraci D, Scaldaferri M, Dellacasa C, Busca A, Dionisi-Vici M, Cattel F, Motta G, Giaccone L, Ghigo E, Arvat E, Lanfranco F, Bruno B, Brignardello E (2021) Impact of allogeneic stem cell transplantation on testicular and sexual function. Transplant Cell Ther 27(2):182.e1-182.e8. https://doi.org/10.1016/j.jtct.2020.10.020CrossRefPubMed

Sanders JE, Hoffmeister PA, Woolfrey AE, Carpenter PA, Storer BE, Storb RF, Appelbaum FR (2009) Thyroid function following hematopoietic cell transplantation in children: 30 years’ experience. Blood 113(2):306–308. https://doi.org/10.1182/blood-2008-08-173005CrossRefPubMedPubMedCentral

Somali M, Mpatakoias V, Avramides A, Sakellari I, Smias Ch, Anagnostopoulos A, Papachristou A, Antoniadou A (2005) Thyroid dysfunction in adult long-term survivors after hemapoeitic stem-cell transplantation (HSCT). Horm Metab Res 37(8):494–499. https://doi.org/10.1055/s-2005-870308CrossRefPubMed

10.

Farhadfar N, Stan MN, Shah P, Sonawane V, Hefazi MT, Murthy HS, Zou F, Sican X, Hashmi SK (2018) Thyroid dysfunction in adult hematopoietic cell transplant survivors: risks and outcomes. Bone Marrow Transpl 53(8):977–982. https://doi.org/10.1038/s41409-018-0109-5CrossRef

11.

Berger C, Le-Gallo B, Donadieu J, Richard O, Devergie A, Galambrun C, Bordigoni P, Vilmer E, Plouvier E, Perel Y, Michel G, Stephan JL (2005) Late thyroid toxicity in 153 long-term survivors of allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. Bone Marrow Transpl 35(10):991–995. https://doi.org/10.1038/sj.bmt.1704945CrossRef

12.

Medinger M, Zeiter D, Heim D, Halter J, Gerull S, Tichelli A, Passweg J, Nigro N (2017) Hypothyroidism following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. Leuk Res 58:43–47. https://doi.org/10.1016/j.leukres.2017.04.003CrossRefPubMed

13.

Savani BN, Koklanaris EK, Le Q, Shenoy A, Goodman S, Barrett AJ (2009) 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 hematologic malignancies. Biol Blood Marrow Transpl 15(3):377–381. https://doi.org/10.1016/j.bbmt.2008.11.032CrossRef

14.

Majhail NS, Rizzo JD, Lee SJ, Aljurf M, Atsuta Y, Bonfim C, Burns LJ, Chaudhri N, Davies S, Okamoto S, Seber A, Socie G, Szer J, Lint MT, Wingard JR, Tichelli A (2012) Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Rev Bras Hematol Hemoter 34(2):109–133. https://doi.org/10.5581/1516-8484.20120032CrossRefPubMedPubMedCentral

15.

Al-Fiar FZ, Colwill R, Lipton JH, Fyles G, Spaner D, Messner H (1997) Abnormal thyroid stimulating hormone (TSH) levels in adults following allogeneic bone marrow transplants. Bone Marrow Transpl 19(10):1019–1022. https://doi.org/10.1038/sj.bmt.1700771CrossRef

16.

Sánchez-Ortega I, Canals C, Peralta T, Parody R, Clapés V, de Sevilla AF, Duarte RF (2012) Thyroid dysfunction in adult patients late after autologous and allogeneic blood and marrow transplantation. Bone Marrow Transpl 47(2):296–298. https://doi.org/10.1038/bmt.2011.54CrossRef

17.

Tauchmanova L, Colao A, Selleri C, De Rosa G, Rotoli B (2006) Thyroid dysfunction after autologous hematopoietic stem cell transplant. Am J Med 119(6):e5-6. https://doi.org/10.1016/j.amjmed.2005.09.017CrossRefPubMed

18.

Akirov A, Sawka AM, Ben-Barouch S, Lipton J, Ezzat S (2019) Endocrine complications in patients with GVHD. Endocr Pract 25(5):485–490. https://doi.org/10.4158/EP-2018-0529CrossRefPubMed

19.

Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME (2015) National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl 21(3):389-401.e1. https://doi.org/10.1016/j.bbmt.2014.12.001CrossRef

20.

Penack O, Marchetti M, Ruutu T, Aljurf M, Bacigalupo A, Bonifazi F, Ciceri F, Cornelissen J, Malladi R, Duarte RF, Giebel S, Greinix H, Holler E, Lawitschka A, Mielke S, Mohty M, Arat M, Nagler A, Passweg J, Schoemans H, Socié G, Solano C, Vrhovac R, Zeiser R, Kröger N, Basak GW (2020) Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 7(2):e157–e167. https://doi.org/10.1016/S2352-3026(19)30256-XCrossRefPubMed

21.

Isshiki Y, Ono K, Shono K, Onoda M, Yokota A (2016) Autoimmune thyroid dysfunction after allogeneic hematopoietic stem cell transplant. Leuk Lymphoma 57(5):1227–1229. https://doi.org/10.3109/10428194.2015.1085532CrossRefPubMed

22.

Ataca Atilla P, Akkus E, Atilla E, Gokmen N, Civriz Bozdag S, Kurt Yuksel M, Toprak SK, Baskal N, Akan H, Demirer T, Topcuoglu P, Arslan O, Ilhan O, Ozcan M, Beksac M, Gurman G (2020) Thyroid dysfunctions in adult patients after allogeneic hematopoietic stem cell transplantation. Clin Transpl 34(10):e14049. https://doi.org/10.1111/ctr.14049CrossRef

23.

Caturegli P, De Remigis A, Rose NR (2014) Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev 13(4–5):391–397. https://doi.org/10.1016/j.autrev.2014.01.007CrossRefPubMed

24.

Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, Okosieme OE (2018) Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 14(5):301–316. https://doi.org/10.1038/nrendo.2018.18CrossRefPubMed

25.

Au WY, Lie AK, Kung AW, Liang R, Hawkins BR, Kwong YL (2005) Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation. Bone Marrow Transpl 35(4):383–388. https://doi.org/10.1038/sj.bmt.1704766CrossRef

26.

Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P (2015) Autoimmune thyroid disorders. Autoimmun Rev 14(2):174–180. https://doi.org/10.1016/j.autrev.2014.10.016CrossRefPubMed

27.

Battipaglia G, Labopin M, Kröger N, Vitek A, Afanasyev B, Hilgendorf I, Schetelig J, Ganser A, Blaise D, Itälä-Remes M, Passweg JR, Bonifazi F, Finke J, Ruggeri A, Nagler A, Mohty M (2019) Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood 134(11):892–899. https://doi.org/10.1182/blood.2019000487CrossRefPubMed

28.

Jereczek-Fossa BA, Alterio D, Jassem J, Gibelli B, Tradati N, Orecchia R (2004) Radiotherapy-induced thyroid disorders. Cancer Treat Rev 30(4):369–384. https://doi.org/10.1016/j.ctrv.2003.12.003CrossRefPubMed

29.

Inskip PD, Veiga LHS, Brenner AV, Sigurdson AJ, Ostroumova E, Chow EJ, Stovall M, Smith SA, Weathers RE, Leisenring W, Robison LL, Armstrong GT, Sklar CA, Lubin JH (2018) Hypothyroidism after radiation therapy for childhood cancer: a report from the childhood cancer survivor study. Radiat Res 190(2):117–132. https://doi.org/10.1667/RR14888.1CrossRefPubMedPubMedCentral

Titel: Impact of allogeneic stem cell transplantation on thyroid function
verfasst von: F. Felicetti
F. Gatti
D. Faraci
D. Rosso
M. Zavattaro
N. Fortunati
L. Marinelli
S. Leone
J. Gill
M. Dionisi-Vici
C. Dellacasa
A. Busca
L. Giaccone
E. Arvat
B. Bruno
E. Brignardello
Publikationsdatum: 08.03.2023
Verlag: Springer International Publishing
Erschienen in: Journal of Endocrinological Investigation / Ausgabe 9/2023
Elektronische ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-023-02039-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Impact of allogeneic stem cell transplantation on thyroid function