Association of Chemotherapy Hydroxyurea and Imbalance of Thyroid Hormones among Sudanese Patients with Chronic Myeloid Leukemia
Authors: Ines Belaiba Aloulo, Amira Hassan AbdAlrahaman Arman , Babeker A. Ahmed, Abdelmoein M. A. Ahmed, Mazza M. L. Mohammed, Jasser Kacem, Yosr Aloulou
BCR-ABL1-positive chronic myelogenous or myeloid leukemia (CML) is identified as a myeloproliferative tumor that is primarily made up of proliferating granulocytes and has the Philadelphia chromosome/translocation t (9;22). Bone marrow and peripheral blood are both impacted by CML. Survivors of the atomic bomb have a higher incidence of CML.Some patients presented with Ph-negative, so they took another type of anti-CML drug; it has been observed that thyroid function tests always deviated from normality among oncology patients, so this study aimed to assess the levels of TFT among both groups to highlight the effect of anti-carcinogenic drugs. The data were analyzed using the Statistical Package of Social Science (SPSS) Version 20.
Objective of the study: To evaluate the thyroid function tests in patients diagnosed with Chronic Myeloid Leukemia treated with tyrosine kinase inhibitors- Shendi.
Method: This cross-sectional study was conducted on patients with CML to assess thyroid function tests (TFT). The study involved CML patients treated with tyrosine kinase inhibitors (ph+ve) and others diagnosed as ph-ve treated with other drugs.
Result:Comparing TFT among ph +ve with results of ph-ve showed that a significant difference was obtained by FT3 only (p-value <0.05), and other hormones, FT4 and TSH, did not show differences (p-value> 0.05) for each. Pearson’s correlation for age and duration of disease with TFT among all CML patients showed that all TFT parameters had negative correlations with age and positive correlations with duration; no significant differences were observed (p-value > 0.05) for each.
Conclusion: This study concluded that FT3 hormone is the only affected TFT parameter in Ph+ve patients compared with Ph-ve patients.
Introduction
Leukemia is a cancer of the blood and bone marrow characterized by the uncontrolled production of abnormal white blood cells, leading to anemia, bleeding disorders, and weakened immunity. Chronic Myeloid Leukemia (CML) is a type of leukemia caused by the formation of the BCR-ABL1 fusion gene, usually resulting from the Philadelphia (Ph) chromosome translocation t(9;22). This genetic abnormality produces a continuously active tyrosine kinase that promotes uncontrolled cell growth. While most CML patients are Philadelphia chromosome-positive (Ph+), some rare cases are Philadelphia chromosome-negative (Ph−) but still possess the BCR-ABL1 fusion gene through complex chromosomal rearrangements.
CML progresses through three stages: chronic phase, accelerated phase, and blast phase. Diagnosis involves blood tests, bone marrow examination, cytogenetic analysis, fluorescence in situ hybridization (FISH), and molecular testing. Common clinical features include leukocytosis, anemia, fatigue, splenomegaly, and occasionally hepatomegaly.
The standard treatment for CML is Tyrosine Kinase Inhibitors (TKIs), which target the BCR-ABL1 protein and have significantly improved patient survival. However, TKIs may cause side effects, including thyroid dysfunction, often presenting as elevated thyroid-stimulating hormone (TSH) levels and altered thyroid hormone metabolism. Some studies suggest that TKI-induced hypothyroidism may be associated with better treatment outcomes.
This cross-sectional study investigated 180 CML patients receiving TKI therapy, including 90 Ph+ and 90 Ph− patients. Blood samples were collected for thyroid function tests (TFTs), including free triiodothyronine (FT3), free thyroxine (FT4), and TSH measurements using ELISA.
The results showed that Ph+ patients had higher average FT3, FT4, and TSH levels than Ph− patients. Statistical analysis revealed a significant difference only in FT3 levels between the two groups (p < 0.001), while FT4 and TSH differences were not significant. No significant differences in thyroid hormone levels were observed between males and females, nor were thyroid hormone levels significantly associated with age or disease duration.
The findings suggest that thyroid abnormalities are relatively common among CML patients receiving TKI therapy, particularly in Ph+ cases. Elevated TSH levels in some patients indicate a tendency toward hypothyroidism, supporting previous evidence that TKIs can affect thyroid function. The study highlights the importance of regular thyroid monitoring in CML patients undergoing long-term TKI treatment to ensure timely detection and management of endocrine complications.
Conclusion
This study concluded among CML patients with different karyotypes, TFTs among Ph +ve were affected more than Ph –ve patients. Gender has no effect on levels of TFTs among CML patients administrated TKIs.
FT3 hormone is the only affected TFT parameter in Ph+ve patients compared with Ph-ve patients.
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