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甲状腺自身免疫和甲状腺功能减退与接受酪氨酸激酶抑制剂治疗的慢性髓性白血病患者的深度分子缓解相关。

Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors.

机构信息

Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, Monserrato, 09042, Cagliari, Italy.

Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.

出版信息

J Endocrinol Invest. 2022 Feb;45(2):291-300. doi: 10.1007/s40618-021-01613-5. Epub 2021 Jul 20.

Abstract

PURPOSE

Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors.

METHODS

We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response.

RESULTS

Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto's thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto's thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto's thyroiditis patients with major molecular response.

CONCLUSIONS

Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

摘要

目的

在实体瘤和血液系统恶性肿瘤的治疗中,酪氨酸激酶抑制剂的使用会导致甲状腺功能改变,包括甲状腺自身免疫的新出现,然而,这种治疗过程中甲状腺改变与慢性髓性白血病的转归之间的关系尚不清楚。本研究的目的是探讨在酪氨酸激酶抑制剂治疗期间,甲状腺改变是否会影响慢性髓性白血病的临床转归。

方法

我们评估了 69 例长期接受酪氨酸激酶抑制剂治疗的慢性髓性白血病患者的甲状腺功能和自身免疫情况,观察了甲状腺异常与疾病分子反应之间的关系。

结果

在研究期间,69 例患者中共有 24 例(34.8%)出现了一种或多种甲状腺异常。有相当高比例的患者(21/69,30.4%)出现了甲状腺自身免疫(甲状腺自身抗体阳性伴超声低回声),而临床和亚临床甲状腺功能减退以及亚临床甲状腺功能亢进的发生率分别为 69 例中的 4 例(5.8%)和 3 例(4.3%)。与第一代酪氨酸激酶抑制剂相比,第二代酪氨酸激酶抑制剂与桥本甲状腺炎显著相关(14/32,43.7%),而第一代酪氨酸激酶抑制剂与桥本甲状腺炎显著相关(7/37,18.9%)(p=0.03)。有趣的是,我们还发现,在深度分子反应患者中,甲状腺功能正常(14/26,53.8%)和甲状腺功能减退桥本甲状腺炎(4/26,15.4%)之间存在显著相关性,与主要分子反应患者的甲状腺功能正常(3/43,7%)和甲状腺功能减退桥本甲状腺炎(0/43,0%)相比(p=0.0001)。

结论

我们的研究证实并扩展了我们对酪氨酸激酶抑制剂对甲状腺影响的认识,表明甲状腺自身免疫在慢性髓性白血病患者长期治疗中经常发生,并与更好的肿瘤学反应相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1496/8783879/bd1eb94469cd/40618_2021_1613_Fig1_HTML.jpg

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