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العنوان
The relationship of serum Growth
Differentiating factor 15 (GDF15) to hepcidin
in post transplant adult Egyptian patients and
its prognostic significance /
المؤلف
Hafez, Mohammad Abd-Allah Shazly.
هيئة الاعداد
باحث / محمد عبدالله شاذلى حافظ
مشرف / محمد عثمان عزازى
مناقش / عمرو محمد صدقى الغماز
مناقش / مصطفى كمال حلمى الرزاز
تاريخ النشر
2021.
عدد الصفحات
185 P. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
أمراض الدم
تاريخ الإجازة
1/1/2021
مكان الإجازة
جامعة عين شمس - كلية الطب - قسم الباطنة العامة وامراض الدم
الفهرس
Only 14 pages are availabe for public view

from 185

from 185

Abstract

Hematopoietic cell transplantation (HCT) is a potentially curative therapeutic approach for a variety of malignant and nonmalignant hematopoietic diseases. When HCT is performed in patients with malignant disorders, preparative or conditioning regimens are administered as part of the procedure to achieve 2 goals: provide sufficient immunoablation to prevent graft rejection and reduce the tumor burden.
Hepcidin, a 25-amino acid antimicrobial peptide synthesized in the liver, is encoded by the HAMP gene and considered the central iron-regulatory hormone that mediates the homeostasis of iron concentrations.
Growth differentiation factor 15 (GDF-15) is a stress responsive member of the transforming growth factor-B (TGF-B) cytokine superfamily. In health GDF-15 is weakly expressed in human tissues. Under pathological conditions, GDF-15 can be produced by many malignant and nonmalignant condition. Inflammatory cytokines such as tumor necrosis factor α or interleukin 6 (IL‐6) induce the mRNA expression of GDF15 in activated macrophages, which suggests that GDF15 could increase during the inflammatory response. So, GDF-15 has thus been widely explored as a biomarker for disease prognosis.
Iron overload is commonly seen in patients with hematological malignancies and patients had bone marrow transplantation leading to production of reactive oxygen species causing organ damage with the production of posttransplantation complications.
In this study, Growth differentiating factor 15 and hepcidin were measured in patients had both types of bone marrow transplantation, autologous and allogenic, 1 year after transplantation so as to assess the relationship between them and late posttransplantation complications including iron overload. The study entolled 23 patients had allogenic BMT and 22 patients had autologous BMT.
The expression of GDF15 hepcidin and ferritin was higher than that of normal controls.
In allogenic transplanted patients in our study, there is a significant statistical difference when comparing the mean level of ferritin, GDF15 and hepcidin in patients with autologous and allogenic bone marrow transplantation with the control group.
There were a statistically significant positive correlation between ferritin level and GDF15 level, ferritin level and Hepcidin level, GDF15 level and hepcidin level.
There were a statistically significant positive correlation between ferritin level and ALT level, ferritin level and AST level. Also, A statistically significant positive correlation was detected between GDF15 level and ALT level, AST level. Also, A statistically significant positive correlation was detected between hepcidin level and ALT level, AST level and ALP level.
A statistically significant positive correlation was detected between ferritin level in allogenic transplanted patients and LDH ,DGF 15 and LDH level , hepcidin and LDH level (P=0.010).
In allogenic transplanted patient in our study, the comparison between ferritin, GDF15 and hepcidin levels in patients with bacterial infections and in patients without bacterial infections, there was no statistically significant difference (P=0.249, 0.181 and 0.537 respectively). Also, the comparison between ferritin, GDF15 and hepcidin levels in patients with viral infections and in patients without viral infections, there was no statistically significant difference (P=0.626, 0.798 and 0.382 respectively).
In our study, comparison between ferritin and GDF15 mean level in patients had acute GVHD with those did not have acute GVHD showed that it was higher in patients with acute GVHD with statistically significant difference, but was statistically non-significant with hepcidin. Also, Comparison between ferritin, GDF15 and hepcidin mean level in allogenic patients had chronic GVHD with those did not have chronic GVHD showed that it was higher in patients with chronic GVHD with statistically significant difference in between.
In autologous transplanted patients in our study, a statistically significant positive correlation was detected between ferritin level and GDF15 level, ferritin level and Hepcidin level, GDF15 level and hepcidin level.
We observed a statistically significant positive correlation between ferritin level in autologous transplanted patients and ALT and AST levels. Also, a statistically significant positive correlation was detected between GDF15 level in autologous transplanted patients and ALT and AST levels. Also, a statistically significant positive correlation was detected between hepcidin level in autologous transplanted patients and ALT and AST levels.
The comparison between ferritin, GDF15 and hepcidin levels in autologous patients with bacterial infections and in patients without bacterial infections was statistically non-significant. Also, comparison between ferritin, GDF15 and hepcidin levels in autologous patients with viral infections and in patients without viral infections was statistically non-significant.
In both allogenic and autologous transplanted patients in our study, a statistically non-significant correlation was detected between ferritin level, GDF15 level and hepcidin level with dose of stem cells, engraftment date, age of patients, WBC, Hb, PLT, bilirubin level, INR and electrolytes of the patients.
These findings promote the previous suggestions about the role of both DGF15 and hepcidin in iron overload, liver dysfunction acute and chronic GVHD post-transplantation, indicating that they are important targets for further investigations. And raise the possibility for using both biomarkers as an indicator of post-transplantation complications.